National Library of Energy BETA

Sample records for u-098 isc bind

  1. IXPUG ISC Documents

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Milfeld, TACC | Download File: isc15phiLBMv3.pdf | pdf | 3 MB Workshop: Optimizing a Seismic Imaging Code on the Intel Xeon Phi July 16, 2015 | Author(s): G Civario, ICHEC |...

  2. IEngage Sustainability in the Curriculum (ISC) Program for Doctoral Students

    E-Print Network [OSTI]

    Texas at Arlington, University of

    1 IEngage Sustainability in the Curriculum (ISC) Program for Doctoral Students Call for Proposals and Community Engagement workgroup of the University Sustainability Committee. The funds will be used to support the development and/or implementation of a course component that addresses sustainability in the community

  3. V-172: ISC BIND RUNTIME_CHECK Error Lets Remote Users Deny Service Against

    Broader source: Energy.gov (indexed) [DOE]

    AFDC Printable Version Share this resource Send a link to EERE: Alternative Fuels Data Center Home Page to someone by E-mail Share EERE: Alternative Fuels Data Center Home Page on Facebook Tweet about EERE: Alternative Fuels Data Center Home Page on Twitter Bookmark EERE: Alternative Fuels Data Center Homesum_a_epg0_fpd_mmcf_m.xls" ,"Available from WebQuantity of Natural GasAdjustmentsShirleyEnergyThe U.S.Lacledeutilities. The Economics ofConduct Cross-Site Scripting Attacks

  4. T-662: ISC BIND Packet Processing Flaw Lets Remote Users Deny Service |

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    AFDC Printable Version Share this resource Send a link to EERE: Alternative Fuels Data Center Home Page to someone by E-mail Share EERE: Alternative Fuels Data Center Home Page on Facebook Tweet about EERE: Alternative Fuels Data Center Home Page on Twitter Bookmark EERE: Alternative Fuels Data Center Home Page on Google Bookmark EERE: Alternative Fuels Data Center Home Page on Delicious RankADVANCED MANUFACTURINGEnergyPlan | Department ofSUPPLEMENTSwitzerland| DepartmentEnergy

  5. U-039: ISC Update: BIND 9 Resolver crashes after logging an error in

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    AFDC Printable Version Share this resource Send a link to EERE: Alternative Fuels Data Center Home Page to someone by E-mail Share EERE: Alternative Fuels Data Center Home Page on Facebook Tweet about EERE: Alternative Fuels Data Center Home Page on Twitter Bookmark EERE: Alternative Fuels Data Center Home Page on Google Bookmark EERE: Alternative Fuels Data Center Home Page on Delicious RankADVANCEDInstallers/ContractorsPhotovoltaicsStateof Energy TwoEvent at the Pu2: AppleGainDepartment

  6. ISC Conventional Reading Rooms | U.S. DOE Office of Science (SC)

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    AFDC Printable Version Share this resource Send a link to EERE: Alternative Fuels Data Center Home Page to someone by E-mail Share EERE: Alternative Fuels Data Center Home Page on Facebook Tweet about EERE: Alternative Fuels Data Center Home Page on Twitter Bookmark EERE: Alternative Fuels Data Center Homesum_a_epg0_fpd_mmcf_m.xls" ,"Available from WebQuantity ofkandz-cm11 Outreach Home Room NewsInformation CurrentHenry Bellamy, Ph.D.FoodHydropower, WaveID-11383 RevisionISC

  7. Information Systems and Computing/Office of Information Security www.upenn.edu/computing/security security@isc.upenn.edu

    E-Print Network [OSTI]

    Fang-Yen, Christopher

    ". And Penn actually offers a couple of "home grown" cloud services for secure file sharing and transferInformation Systems and Computing/Office of Information Security www.upenn.edu/computing/security security@isc.upenn.edu "phishing"...? Information Systems and Computing/Office of Information Security

  8. A review of the new ISC-PRIME model and implications for power plant licensing in Maryland

    SciTech Connect (OSTI)

    Gill, S.; Garrison, M.; Sherwell, J.

    1999-07-01

    The Maryland Department of Natural Resources (DNR) Power Plant Research Program (PPRP) manages the consolidated review of environmental, engineering, socioeconomic, cost, and need issues that new and modified power plants in Maryland must address as part of the power plant licensing process. Power plant licensing cases in Maryland have included the addition or replacement of small diesel or combustion turbine electrical generation units, or the addition of new, larger simple-cycle combustion turbine units. Air quality modeling, including an assessment of the effects of building downwash, is often a part of the licensing process. The Electric Power Research Institute (EPRI) has sponsored the development of an improved building downwash model through its PRIME (Plume Rise Model Enhancements) project, involving the design and development of algorithms intended to address deficiencies in the widely used ISCST3. EPA recently provided a version of ISC that incorporates the PRIME model (ISC-PRIME) for review and comment by the public prior to deciding on the suitability and regulatory status of ISC-PRIME. The present paper focuses on a systematic evaluation of ISC-PRIME as it relates to short stacks with exhaust characteristics similar to diesel generators and combustion turbines, using both routine hourly meteorology and synthesized meteorological data covering a wide variety of stability and wind speed combinations. The goals of the paper are two-fold: first, to understand and explain the implications of this new model for power plant licensing decisions in the State of Maryland; and second, to broaden the experience base of the potential ISC-PRIME user community with information on model performance details that are not otherwise readily available.

  9. Intrinsic Radiation Source Generation with the ISC Package: Data Comparisons and Benchmarking

    SciTech Connect (OSTI)

    Solomon, Clell J. Jr.

    2012-04-26

    The characterization of radioactive emissions from unstable isotopes (intrinsic radiation) is necessary for shielding and radiological-dose calculations from radioactive materials. While most radiation transport codes, e.g., MCNP [X-5 Monte Carlo Team, 2003], provide the capability to input user prescribed source definitions, such as radioactive emissions, they do not provide the capability to calculate the correct radioactive-source definition given the material compositions. Special modifications to MCNP have been developed in the past to allow the user to specify an intrinsic source, but these modification have not been implemented into the primary source base [Estes et al., 1988]. To facilitate the description of the intrinsic radiation source from a material with a specific composition, the Intrinsic Source Constructor library (LIBISC) and MCNP Intrinsic Source Constructor (MISC) utility have been written. The combination of LIBISC and MISC will be herein referred to as the ISC package. LIBISC is a statically linkable C++ library that provides the necessary functionality to construct the intrinsic-radiation source generated by a material. Furthermore, LIBISC provides the ability use different particle-emission databases, radioactive-decay databases, and natural-abundance databases allowing the user flexibility in the specification of the source, if one database is preferred over others. LIBISC also provides functionality for aging materials and producing a thick-target bremsstrahlung photon source approximation from the electron emissions. The MISC utility links to LIBISC and facilitates the description of intrinsic-radiation sources into a format directly usable with the MCNP transport code. Through a series of input keywords and arguments the MISC user can specify the material, age the material if desired, and produce a source description of the radioactive emissions from the material in an MCNP readable format. Further details of using the MISC utility can be obtained from the user guide [Solomon, 2012]. The remainder of this report presents a discussion of the databases available to LIBISC and MISC, a discussion of the models employed by LIBISC, a comparison of the thick-target bremsstrahlung model employed, a benchmark comparison to plutonium and depleted-uranium spheres, and a comparison of the available particle-emission databases.

  10. Towards an InTerdIscIplInary approach To nexT-GeneraTIon BIofuels EnvironmEntal, tEchno-Economic, and GovErnancE

    E-Print Network [OSTI]

    Iglesia, Enrique

    Towards an InTerdIscIplInary approach To nexT-GeneraTIon BIofuels EnvironmEntal, t. 2010. The Ecological Impact of Biofuels. Pages 351-377 in D. J. Futuyma, H. B. Shafer, and D. Huffer, S., Roche, C.M., Blanch, H.W., and Clark, D.S. (2012). Escherichia coli for biofuel production

  11. IXPUG ISC Documents

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Thomas Steinke, ZIB | Download File: 1Welcome.pdf | pdf | 98 KB BoF: Performance Optimization of OpenFOAM on XeonXeon Phi July 15, 2015 | Author(s): Nishant Agrawal | Download...

  12. IXPUG ISC15 Documents

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    AFDC Printable Version Share this resource Send a link to EERE: Alternative Fuels Data Center Home Page to someone by E-mail Share EERE: Alternative Fuels Data Center Home Page on Facebook Tweet about EERE: Alternative Fuels Data Center Home Page on Twitter Bookmark EERE: Alternative Fuels Data Center Homesum_a_epg0_fpd_mmcf_m.xls" ,"Available from WebQuantity ofkandz-cm11 Outreach Home Room NewsInformation CurrentHenry Bellamy, Ph.D.FoodHydropower,

  13. IXPUG ISC15 Documents

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    AFDC Printable Version Share this resource Send a link to EERE: Alternative Fuels Data Center Home Page to someone by E-mail Share EERE: Alternative Fuels Data Center Home Page on Facebook Tweet about EERE: Alternative Fuels Data Center Home Page on Twitter Bookmark EERE: Alternative Fuels Data Center Homesum_a_epg0_fpd_mmcf_m.xls" ,"Available from WebQuantityBonneville Power Administration would likeUniverse (JournalvivoHighHussein KhalilResearch88 Sign In About |ITEMIntel® Xeon

  14. IXPUG ISC15 Documents

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    AFDC Printable Version Share this resource Send a link to EERE: Alternative Fuels Data Center Home Page to someone by E-mail Share EERE: Alternative Fuels Data Center Home Page on Facebook Tweet about EERE: Alternative Fuels Data Center Home Page on Twitter Bookmark EERE: Alternative Fuels Data Center Homesum_a_epg0_fpd_mmcf_m.xls" ,"Available from WebQuantityBonneville Power Administration would likeUniverse (JournalvivoHighHussein KhalilResearch88 Sign In About |ITEMIntel®

  15. IXPUG ISC15 Documents

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    AFDC Printable Version Share this resource Send a link to EERE: Alternative Fuels Data Center Home Page to someone by E-mail Share EERE: Alternative Fuels Data Center Home Page on Facebook Tweet about EERE: Alternative Fuels Data Center Home Page on Twitter Bookmark EERE: Alternative Fuels Data Center Homesum_a_epg0_fpd_mmcf_m.xls" ,"Available from WebQuantityBonneville Power Administration would likeUniverse (JournalvivoHighHussein KhalilResearch88 Sign In About

  16. IXPUG ISC15 Documents

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    AFDC Printable Version Share this resource Send a link to EERE: Alternative Fuels Data Center Home Page to someone by E-mail Share EERE: Alternative Fuels Data Center Home Page on Facebook Tweet about EERE: Alternative Fuels Data Center Home Page on Twitter Bookmark EERE: Alternative Fuels Data Center Homesum_a_epg0_fpd_mmcf_m.xls" ,"Available from WebQuantityBonneville Power Administration would likeUniverse (JournalvivoHighHussein KhalilResearch88 Sign In AboutWorkshop: Language

  17. Hanna, S.R., D. Heinold, R. Paine, H.C. Frey, D. Baker, R. Karp, and H. Feldman, "A Monte Carlo Study of the Uncertainties in Predictions by ISC3ST and AERMOD of Annual Average Benzene and 1,3-Butadiene Concentrations

    E-Print Network [OSTI]

    Frey, H. Christopher

    Study of the Uncertainties in Predictions by ISC3ST and AERMOD of Annual Average Benzene and 1 of Annual Average Benzene and 1,3-Butadiene Concentrations around the Houston Ship Channel Control # 735 is on uncertainties in ISC3ST and AERMOD predictions of annual averaged concentrations of benzene and 1,3-butadiene

  18. ISC2005v2.ppt

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    AFDC Printable Version Share this resource Send a link to EERE: Alternative Fuels Data Center Home Page to someone by E-mail Share EERE: Alternative Fuels Data Center Home Page on Facebook Tweet about EERE: Alternative Fuels Data Center Home Page on Twitter Bookmark EERE: Alternative Fuels Data Center Homesum_a_epg0_fpd_mmcf_m.xls" ,"Available from WebQuantityBonneville Power Administration would likeUniverse (JournalvivoHighHussein KhalilResearch88 Sign In About | Workshop for

  19. Cellulose binding domain proteins

    DOE Patents [OSTI]

    Shoseyov, Oded (Karmey Yosef, IL); Shpiegl, Itai (Rehovot, IL); Goldstein, Marc (Davis, CA); Doi, Roy (Davis, CA)

    1998-01-01

    A cellulose binding domain (CBD) having a high affinity for crystalline cellulose and chitin is disclosed, along with methods for the molecular cloning and recombinant production thereof. Fusion products comprising the CBD and a second protein are likewise described. A wide range of applications are contemplated for both the CBD and the fusion products, including drug delivery, affinity separations, and diagnostic techniques.

  20. Cellulose binding domain proteins

    DOE Patents [OSTI]

    Shoseyov, O.; Shpiegl, I.; Goldstein, M.; Doi, R.

    1998-11-17

    A cellulose binding domain (CBD) having a high affinity for crystalline cellulose and chitin is disclosed, along with methods for the molecular cloning and recombinant production. Fusion products comprising the CBD and a second protein are likewise described. A wide range of applications are contemplated for both the CBD and the fusion products, including drug delivery, affinity separations, and diagnostic techniques. 16 figs.

  1. Synthetic heparin-binding growth factor analogs

    DOE Patents [OSTI]

    Pena, Louis A.; Zamora, Paul; Lin, Xinhua; Glass, John D.

    2007-01-23

    The invention provides synthetic heparin-binding growth factor analogs having at least one peptide chain that binds a heparin-binding growth factor receptor, covalently bound to a hydrophobic linker, which is in turn covalently bound to a non-signaling peptide that includes a heparin-binding domain. The synthetic heparin-binding growth factor analogs are useful as soluble biologics or as surface coatings for medical devices.

  2. Cellulose binding domain fusion proteins

    DOE Patents [OSTI]

    Shoseyov, O.; Yosef, K.; Shpiegl, I.; Goldstein, M.A.; Doi, R.H.

    1998-02-17

    A cellulose binding domain (CBD) having a high affinity for crystalline cellulose and chitin is disclosed, along with methods for the molecular cloning and recombinant production. Fusion products comprising the CBD and a second protein are likewise described. A wide range of applications are contemplated for both the CBD and the fusion products, including drug delivery, affinity separations, and diagnostic techniques. 16 figs.

  3. Cellulose binding domain fusion proteins

    DOE Patents [OSTI]

    Shoseyov, Oded (Karmey Yosef, IL); Shpiegl, Itai (Rehovot, IL); Goldstein, Marc A. (Davis, CA); Doi, Roy H. (Davis, CA)

    1998-01-01

    A cellulose binding domain (CBD) having a high affinity for crystalline cellulose and chitin is disclosed, along with methods for the molecular cloning and recombinant production thereof. Fusion products comprising the CBD and a second protein are likewise described. A wide range of applications are contemplated for both the CBD and the fusion products, including drug delivery, affinity separations, and diagnostic techniques.

  4. Erythropoietin binding protein from mammalian serum

    DOE Patents [OSTI]

    Clemons, Gisela K. (Berkeley, CA)

    1997-01-01

    Purified mammalian erythropoietin binding-protein is disclosed, and its isolation, identification, characterization, purification, and immunoassay are described. The erythropoietin binding protein can be used for regulation of erythropoiesis by regulating levels and half-life of erythropoietin. A diagnostic kit for determination of level of erythropoietin binding protein is also described.

  5. Erythropoietin binding protein from mammalian serum

    DOE Patents [OSTI]

    Clemons, G.K.

    1997-04-29

    Purified mammalian erythropoietin binding-protein is disclosed, and its isolation, identification, characterization, purification, and immunoassay are described. The erythropoietin binding protein can be used for regulation of erythropoiesis by regulating levels and half-life of erythropoietin. A diagnostic kit for determination of level of erythropoietin binding protein is also described. 11 figs.

  6. A Rare Earth-DOTA-Binding Antibody: Probe Properties and Binding Affinity across the Lanthanide Series

    E-Print Network [OSTI]

    Fisher, Andrew J.

    1) binds transition metals and rare earths with extreme stability under physiological conditionsA Rare Earth-DOTA-Binding Antibody: Probe Properties and Binding Affinity across the Lanthanide affinity and exquisite specificity.1 An antibody that binds rare earth complexes selectively could be used

  7. Synthetic heparin-binding factor analogs

    DOE Patents [OSTI]

    Pena, Louis A. (Poquott, NY); Zamora, Paul O. (Gaithersburg, MD); Lin, Xinhua (Plainview, NY); Glass, John D. (Shoreham, NY)

    2010-04-20

    The invention provides synthetic heparin-binding growth factor analogs having at least one peptide chain, and preferably two peptide chains branched from a dipeptide branch moiety composed of two trifunctional amino acid residues, which peptide chain or chains bind a heparin-binding growth factor receptor and are covalently bound to a non-signaling peptide that includes a heparin-binding domain, preferably by a linker, which may be a hydrophobic linker. The synthetic heparin-binding growth factor analogs are useful as pharmaceutical agents, soluble biologics or as surface coatings for medical devices.

  8. Docking Small Ligands in Flexible Binding Sites

    E-Print Network [OSTI]

    Caflisch, Amedeo

    binding site. For all three systems the best minima in terms of free energy have a root mean square 3100-043423.95 Contractrgrant sponsor: Swiss Federal Office of Public Health; contractrgrant number the conformational space that has to be searched. There are known examples where the empty receptor cannot bind

  9. Improved flow cytometer measurement of binding assays

    DOE Patents [OSTI]

    Saunders, G.C.

    1984-05-30

    The invention relates to a method of measuring binding assays carried out with different size particles wherein the binding assay sample is run through a flow cytometer without separating the sample from the marking agent. The amount of a binding reactant present in a sample is determined by providing particles with a coating of binder and also a known quantity of smaller particles with a coating of binder reactant. The binding reactant is the same as the binding reactant present in the sample. The smaller particles also contain a fluorescent chemical. The particles are combined with the sample and the binding reaction is allowed to occur for a set length of time followed by combining the smaller particles with the mixture of the particles and the sample produced and allowing the binding reactions to proceed to equilibrium. The fluorescence and light scatter of the combined mixture is then measured as the combined mixture passes through a flow cytometer equipped with a laser to bring about fluorescence, and the number and strength of fluorescent events are compared. A similar method is also provided for determining the amount of antigen present in the sample by providing spheres with an antibody coating and some smaller spheres with an antigen coating. (LEW)

  10. Bipolaron and N-Polaron Binding Energies

    SciTech Connect (OSTI)

    Frank, Rupert L. [Department of Mathematics, Princeton University, Washington Road, Princeton, New Jersey 08544 (United States); Lieb, Elliott H. [Department of Mathematics, Princeton University, Washington Road, Princeton, New Jersey 08544 (United States); Department of Physics, Princeton University, P.O. Box 708, Princeton, New Jersey 08542 (United States); Seiringer, Robert [Department of Physics, Princeton University, P.O. Box 708, Princeton, New Jersey 08542 (United States); Thomas, Lawrence E. [Department of Mathematics, University of Virginia, Charlottesville, Virginia 22904 (United States)

    2010-05-28

    The binding of polarons, or its absence, is an old and subtle topic. Here we prove two things rigorously. First, the transition from many-body collapse to the existence of a thermodynamic limit for N polarons occurs precisely at U=2{alpha}, where U is the electronic Coulomb repulsion and {alpha} is the polaron coupling constant. Second, if U is large enough, there is no multipolaron binding of any kind. Considering the known fact that there is binding for some U>2{alpha}, these conclusions are not obvious and their proof has been an open problem for some time.

  11. Sequestering Uranium from Seawater: Binding Strength and Modes...

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Sequestering Uranium from Seawater: Binding Strength and Modes of Uranyl Complexes with Glutarimidedioxime Sequestering Uranium from Seawater: Binding Strength and Modes of Uranyl...

  12. Metal-binding polymesr as chelating agents

    E-Print Network [OSTI]

    Mohammadi, Zahra

    2011-04-11

    , high affinity binding of toxic metals by these functionalized hydrogels offers potential applications in waste water treatment and may enable applications in acute metal poisoning. Finally, a unique synthetic methodology using similar metal chelating...

  13. Hardware device binding and mutual authentication

    DOE Patents [OSTI]

    Hamlet, Jason R; Pierson, Lyndon G

    2014-03-04

    Detection and deterrence of device tampering and subversion by substitution may be achieved by including a cryptographic unit within a computing device for binding multiple hardware devices and mutually authenticating the devices. The cryptographic unit includes a physically unclonable function ("PUF") circuit disposed in or on the hardware device, which generates a binding PUF value. The cryptographic unit uses the binding PUF value during an enrollment phase and subsequent authentication phases. During a subsequent authentication phase, the cryptographic unit uses the binding PUF values of the multiple hardware devices to generate a challenge to send to the other device, and to verify a challenge received from the other device to mutually authenticate the hardware devices.

  14. RNA binding protein and binding site useful for expression of recombinant molecules

    DOE Patents [OSTI]

    Mayfield, Stephen (Cardiff, CA)

    2000-01-01

    The present invention relates to a gene expression system in eukaryotic and prokaryotic cells, preferably plant cells and intact plants. In particular, the invention relates to an expression system having a RB47 binding site upstream of a translation initiation site for regulation of translation mediated by binding of RB47 protein, a member of the poly(A) binding protein family. Regulation is further effected by RB60, a protein disulfide isomerase. The expression system is capable of functioning in the nuclear/cytoplasm of cells and in the chloroplast of plants. Translation regulation of a desired molecule is enhanced approximately 100 fold over that obtained without RB47 binding site activation.

  15. RNA binding protein and binding site useful for expression of recombinant molecules

    DOE Patents [OSTI]

    Mayfield, Stephen P.

    2006-10-17

    The present invention relates to a gene expression system in eukaryotic and prokaryotic cells, preferably plant cells and intact plants. In particular, the invention relates to an expression system having a RB47 binding site upstream of a translation initiation site for regulation of translation mediated by binding of RB47 protein, a member of the poly(A) binding protein family. Regulation is further effected by RB60, a protein disulfide isomerase. The expression system is capable of functioning in the nuclear/cytoplasm of cells and in the chloroplast of plants. Translation regulation of a desired molecule is enhanced approximately 100 fold over that obtained without RB47 binding site activation.

  16. Introduction to Clients and Servers CSC 120 / ISC 150

    E-Print Network [OSTI]

    Wenderholm, Elaine

    Department SUNY Oswego c 2010 Elaine Wenderholm All Rights Reserved ­ p.1/15 #12;The World Wide Web and HTML Rights Reserved ­ p.2/15 #12;The World Wide Web and HTML Early 1990s at CERN particle physics laboratory Wide Web and HTML Early 1990s at CERN particle physics laboratory in Geneva, Switzerland

  17. ISC-Reducing Congestion through Smart Parking Management | Open Energy

    Open Energy Info (EERE)

    AFDC Printable Version Share this resource Send a link to EERE: Alternative Fuels Data Center Home Page to someone by E-mail Share EERE: Alternative Fuels Data Center Home Page on Facebook Tweet about EERE: Alternative Fuels Data Center Home Page on Twitter Bookmark EERE: Alternative Fuels Data Center Home Page on Google Bookmark EERE: Alternative Fuels Data Center Home Page on QA:QA J-E-1 SECTION J APPENDIX E LISTStar2-0057-EA JumpDuimen RiverScoringUtilities CommEnergy,INTAIRENA

  18. Institute for Sustainable Communities (ISC) | Open Energy Information

    Open Energy Info (EERE)

    AFDC Printable Version Share this resource Send a link to EERE: Alternative Fuels Data Center Home Page to someone by E-mail Share EERE: Alternative Fuels Data Center Home Page on Facebook Tweet about EERE: Alternative Fuels Data Center Home Page on Twitter Bookmark EERE: Alternative Fuels Data Center Home Page on Google Bookmark EERE: Alternative Fuels Data Center Home Page on QA:QA J-E-1 SECTION J APPENDIXsource History View NewGuam:on Openei |sourceAndInformationInstalled

  19. ISC-Chicago Office Environmental Assessments (EA) / Environmental Impact

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    AFDC Printable Version Share this resource Send a link to EERE: Alternative Fuels Data Center Home Page to someone by E-mail Share EERE: Alternative Fuels Data Center Home Page on Facebook Tweet about EERE: Alternative Fuels Data Center Home Page on Twitter Bookmark EERE: Alternative Fuels Data Center Homesum_a_epg0_fpd_mmcf_m.xls" ,"Available from WebQuantityBonneville Power Administration would likeUniverse (JournalvivoHighHussein KhalilResearch88 Sign In About | CareersOffice

  20. ISC-Oak Ridge Office Environmental Assessments (EA) / Environmental Impact

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    AFDC Printable Version Share this resource Send a link to EERE: Alternative Fuels Data Center Home Page to someone by E-mail Share EERE: Alternative Fuels Data Center Home Page on Facebook Tweet about EERE: Alternative Fuels Data Center Home Page on Twitter Bookmark EERE: Alternative Fuels Data Center Homesum_a_epg0_fpd_mmcf_m.xls" ,"Available from WebQuantityBonneville Power Administration would likeUniverse (JournalvivoHighHussein KhalilResearch88 Sign In About |

  1. ISC15 Workshop for Intel® Xeon Phi

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    AFDC Printable Version Share this resource Send a link to EERE: Alternative Fuels Data Center Home Page to someone by E-mail Share EERE: Alternative Fuels Data Center Home Page on Facebook Tweet about EERE: Alternative Fuels Data Center Home Page on Twitter Bookmark EERE: Alternative Fuels Data Center Homesum_a_epg0_fpd_mmcf_m.xls" ,"Available from WebQuantityBonneville Power Administration would likeUniverse (JournalvivoHighHussein KhalilResearch88 Sign In About | Workshop for Intel®

  2. Estrophilin immunoreactivity versus estrogen receptor binding activity in meningiomas: evidence for multiple estrogen binding sites

    SciTech Connect (OSTI)

    Lesch, K.P.; Schott, W.; Gross, S.

    1987-09-01

    The existence of estrogen receptors in human meningiomas has long been a controversial issue. This may be explained, in part, by apparent heterogeneity of estrogen binding sites in meningioma tissue. In this study, estrogen receptors were determined in 58 meningiomas with an enzyme immunoassay using monoclonal antibodies against human estrogen receptor protein (estrophilin) and with a sensitive radioligand binding assay using /sup 125/I-labeled estradiol (/sup 125/I-estradiol) as radioligand. Low levels of estrophilin immunoreactivity were found in tumors from 62% of patients, whereas radioligand binding activity was demonstrated in about 46% of the meningiomas examined. In eight (14%) tissue samples multiple binding sites for estradiol were observed. The immunoreactive binding sites correspond to the classical, high affinity estrogen receptors: the Kd for /sup 125/I-estradiol binding to the receptor was approximately 0.2 nM and the binding was specific for estrogens. The second, low affinity class of binding sites considerably influenced measurement of the classical receptor even at low ligand concentrations. The epidemiological and clinical data from patients with meningiomas, and the existence of specific estrogen receptors confirmed by immunochemical detection, may be important factors in a theory of oncogenesis.

  3. Annual Meeting of the ISCE 23-27 July, 2005 Annual Meeting of the ISCE 23-27 July, 2005

    E-Print Network [OSTI]

    Rasmont, Pierre

    .webresourcesdepot.comInstructor Winter 2014 Class: Thursday 5:00PM-7:50PM; 4824 ELLISON HALL Professor David Lpez-Carr carr

  4. Binding Energies in Nonrelativistic Field Theories

    E-Print Network [OSTI]

    Andreas S. Kronfeld

    1996-08-26

    Relativistic corrections communicate the binding energy of a bound state to its kinetic mass. This mechanism is reviewed and used to explain anomalous results of Collins, Edwards, Heller, and Sloan (hep-lat/9512026), which compared rest and kinetic masses of heavy-light mesons and quarkonia.

  5. Nucleic acids encoding a cellulose binding domain

    DOE Patents [OSTI]

    Shoseyov, O.; Shpiegl, I.; Goldstein, M.A.; Doi, R.H.

    1996-03-05

    A cellulose binding domain (CBD) having a high affinity for crystalline cellulose and chitin is disclosed, along with methods for the molecular cloning and recombinant production. Fusion products comprising the CBD and a second protein are likewise described. A wide range of applications are contemplated for both the CBD and the fusion products, including drug delivery, affinity separations, and diagnostic techniques. 15 figs.

  6. BOUND SYSTEMS 4.A Binding Energy

    E-Print Network [OSTI]

    Boal, David

    CHAPTER 4 BOUND SYSTEMS 4.A Binding Energy The mass-energy equation (3.2) is valid for a single linear momentum and its energy. While we introduced the equation in order to describe the energy is measurable. The implication of (4.1) taken with (3.2) is that the mass energy of a bound state is less than

  7. Nucleic acids encoding a cellulose binding domain

    DOE Patents [OSTI]

    Shoseyov, Oded (Karmey Yosef, IL); Shpiegl, Itai (Rehovot, IL); Goldstein, Marc A. (Davis, CA); Doi, Roy H. (Davis, CA)

    1996-01-01

    A cellulose binding domain (CBD) having a high affinity for crystalline cellulose and chitin is disclosed, along with methods for the molecular cloning and recombinant production thereof. Fusion products comprising the CBD and a second protein are likewise described. A wide range of applications are contemplated for both the CBD and the fusion products, including drug delivery, affinity separations, and diagnostic techniques.

  8. Study of fragmentation using clusterization algorithm with realistic binding energies

    E-Print Network [OSTI]

    Yogesh K. Vermani; Jatinder K. Dhawan; Supriya Goyal; Rajeev K. Puri; J. Aichelin

    2009-12-28

    We here study fragmentation using \\emph{simulated annealing clusterization algorithm} (SACA) with binding energy at a microscopic level. In an earlier version, a constant binding energy (4 MeV/nucleon) was used. We improve this binding energy criterion by calculating the binding energy of different clusters using modified Bethe-Weizs\\"{a}cker mass (BWM) formula. We also compare our calculations with experimental data of ALADiN group. Nearly no effect is visible of this modification.

  9. Predicting Metal-Binding Sites from Protein Sequence

    E-Print Network [OSTI]

    Passerini, Andrea

    Predicting Metal-Binding Sites from Protein Sequence Andrea Passerini, Marco Lippi, and Paolo algorithmic ideas based on structured- output learning for determining transition-metal-binding sites coordinate more than one metal ion, we prove that metal binding has the algebraic structure of a matroid

  10. Dual chain synthetic heparin-binding growth factor analogs

    DOE Patents [OSTI]

    Zamora, Paul O. (Gaithersburg, MD); Pena, Louis A. (Poquott, NY); Lin, Xinhua (Plainview, NY)

    2012-04-24

    The invention provides synthetic heparin-binding growth factor analogs having two peptide chains each branched from a branch moiety, such as trifunctional amino acid residues, the branch moieties separated by a first linker of from 3 to about 20 backbone atoms, which peptide chains bind a heparin-binding growth factor receptor and are covalently bound to a non-signaling peptide that includes a heparin-binding domain, preferably by a second linker, which may be a hydrophobic second linker. The synthetic heparin-binding growth factor analogs are useful as pharmaceutical agents, soluble biologics or as surface coatings for medical devices.

  11. Dual chain synthetic heparin-binding growth factor analogs

    DOE Patents [OSTI]

    Zamora, Paul O. (Gaithersburg, MD); Pena, Louis A. (Poquott, NY); Lin, Xinhua (Plainview, NY)

    2009-10-06

    The invention provides synthetic heparin-binding growth factor analogs having two peptide chains each branched from a branch moiety, such as trifunctional amino acid residues, the branch moieties separated by a first linker of from 3 to about 20 backbone atoms, which peptide chains bind a heparin-binding growth factor receptor and are covalently bound to a non-signaling peptide that includes a heparin-binding domain, preferably by a second linker, which may be a hydrophobic second linker. The synthetic heparin-binding growth factor analogs are useful as pharmaceutical agents, soluble biologics or as surface coatings for medical devices.

  12. Polynucleotides encoding TRF1 binding proteins

    DOE Patents [OSTI]

    Campisi, Judith (Berkeley, CA); Kim, Sahn-Ho (Albany, CA)

    2002-01-01

    The present invention provides a novel telomere associated protein (Trf1-interacting nuclear protein 2 "Tin2") that hinders the binding of Trf1 to its specific telomere repeat sequence and mediates the formation of a Tin2-Trf1-telomeric DNA complex that limits telomerase access to the telomere. Also included are the corresponding nucleic acids that encode the Tin2 of the present invention, as well as mutants of Tin2. Methods of making, purifying and using Tin2 of the present invention are described. In addition, drug screening assays to identify drugs that mimic and/or complement the effect of Tin2 are presented.

  13. Hardware device to physical structure binding and authentication

    SciTech Connect (OSTI)

    Hamlet, Jason R.; Stein, David J.; Bauer, Todd M.

    2013-08-20

    Detection and deterrence of device tampering and subversion may be achieved by including a cryptographic fingerprint unit within a hardware device for authenticating a binding of the hardware device and a physical structure. The cryptographic fingerprint unit includes an internal physically unclonable function ("PUF") circuit disposed in or on the hardware device, which generate an internal PUF value. Binding logic is coupled to receive the internal PUF value, as well as an external PUF value associated with the physical structure, and generates a binding PUF value, which represents the binding of the hardware device and the physical structure. The cryptographic fingerprint unit also includes a cryptographic unit that uses the binding PUF value to allow a challenger to authenticate the binding.

  14. Crown Ethers Flatten in Graphene for Strong, Specific Binding...

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    2011 2010 News Home | ORNL | News | Features | 2014 SHARE Crown Ethers Flatten in Graphene for Strong, Specific Binding ORNL discovery holds potential for separations, sensors,...

  15. Neptunium Binding Kinetics with Arsenazo(III)

    SciTech Connect (OSTI)

    Leigh R. Martin; Aaron T. Johnson; Stephen P. Mezyk

    2014-08-01

    This document has been prepared to meet FCR&D level 2 milestone M2FT-14IN0304021, Report on the results of actinide binding kinetics with aqueous phase complexants This work was carried out under the auspices of the Thermodynamics and Kinetics of Advanced Separations Systems FCR&D work package. The report details kinetics experiments that were performed to measure rates of aqueous phase complexation for pentavalent neptunium with the chromotropic dye Arsenazo III (AAIII). The studies performed were designed to determine how pH, ionic strength and AAIII concentration may affect the rate of the reaction. A brief comparison with hexavalent neptunium is also made. It was identified that as pH was increased the rate of reaction also increased, however increasing the ionic strength and concentration of AAIII had the opposite effect. Interestingly, the rate of reaction of Np(VI) with AAIII was found to be slower than that of the Np(V) reaction.

  16. Chemomechanical mapping of ligandreceptor binding kinetics on cells

    E-Print Network [OSTI]

    Van Vliet, Krystyn J.

    Chemomechanical mapping of ligandreceptor binding kinetics on cells Sunyoung Lee, Jelena Mandic, Providence, RI, April 23, 2007 (received for review January 2, 2007) The binding kinetics between cell activity. Modeling and prediction of receptor-mediated cell func- tions are facilitated by measurement

  17. Water at biomolecular binding interfaces Zheng Li and Themis Lazaridis*

    E-Print Network [OSTI]

    Lazaridis, Themis

    Water at biomolecular binding interfaces Zheng Li and Themis Lazaridis* Received 29th August 2006.1039/b612449f Water molecules are often found at the binding interface of biomolecular complexes Waals interactions. Recent studies have demonstrated the importance of taking such water molecules

  18. Hydrogen Bonding Penalty upon Ligand Binding Hongtao Zhao, Danzhi Huang*

    E-Print Network [OSTI]

    Caflisch, Amedeo

    Hydrogen Bonding Penalty upon Ligand Binding Hongtao Zhao, Danzhi Huang* Department of Biochemistry, University of Zurich, Zurich, Switzerland Abstract Ligand binding involves breakage of hydrogen bonds with water molecules and formation of new hydrogen bonds between protein and ligand. In this work, the change

  19. ORIGINAL ARTICLE Analysis of RUNX1 binding site and RAPTOR

    E-Print Network [OSTI]

    Abecasis, Goncalo

    ORIGINAL ARTICLE Analysis of RUNX1 binding site and RAPTOR polymorphisms in psoriasis: no evidence psoriasis and single nucleotide polymorphisms (SNPs) mapping to distal chromosome 17q, including a disease for the previously identified RUNX1 binding site or for the RAPTOR locus as genetic determinants of psoriasis

  20. Performance-Guided Character Bind Pose for Deformations

    E-Print Network [OSTI]

    Pena, Benito

    2011-08-08

    Current production methods for creating a motion system for a deformable digital character model involve providing an underlying joint structure based o of a T-Pose, A-Pose or another arbitrary bind pose of the character. A bind pose is required...

  1. NUCLEAR FISSION AND FUSION 6.A Nuclear Binding Energies

    E-Print Network [OSTI]

    Boal, David

    CHAPTER 6 NUCLEAR FISSION AND FUSION 6.A Nuclear Binding Energies A nucleus is characterized emphasis on the nuclear charge, the mass number of a nucleus plays a large role in its binding energy, and is denoted by 7Li. Some further items from the nuclear lexicon: nuclei with the same Z and differing N

  2. Calcium Binding by the N-Terminal Cellulose-Binding Domain from Cellulomonas fimi -1,4-Glucanase CenC

    E-Print Network [OSTI]

    McIntosh, Lawrence P.

    Calcium Binding by the N-Terminal Cellulose-Binding Domain from Cellulomonas fimi -1,4-Glucanase, 1998 ABSTRACT: The interaction of the N-terminal cellulose-binding domain, CBDN1, from Cellulomonas-state stability. Enzymes that degrade cellulose often contain one or more domains that mediate binding

  3. Characterization of the Carbohydrate Binding Module 18 gene family in the amphibian pathogen Batrachochytrium dendrobatidis.

    E-Print Network [OSTI]

    Liu, Peng; Stajich, Jason E

    2015-01-01

    a! chitin9binding! module. ! Appl! Microbiol! Biotechnol. !Species9specific! chitin9binding! module! 18! expansion! in!of the Carbohydrate Binding Module 18 gene family in the

  4. Page 1 A dedicated binding mechanism for the visual control of movement

    E-Print Network [OSTI]

    Diedrichsen, Jrn

    Page 1 A dedicated binding mechanism for the visual control of movement results therefore suggest the existence of a dedicated visuo-motor binding mechanism visual target information A dedicated visuo-motor binding mechanism links visual

  5. Structural and Histone Binding Ability Characterizations of Human PWWP Domains

    SciTech Connect (OSTI)

    Wu, Hong; Zeng, Hong; Lam, Robert; Tempel, Wolfram; Amaya, Maria F.; Xu, Chao; Dombrovski, Ludmila; Qiu, Wei; Wang, Yanming; Min, Jinrong (Toronto); (Penn)

    2013-09-25

    The PWWP domain was first identified as a structural motif of 100-130 amino acids in the WHSC1 protein and predicted to be a protein-protein interaction domain. It belongs to the Tudor domain 'Royal Family', which consists of Tudor, chromodomain, MBT and PWWP domains. While Tudor, chromodomain and MBT domains have long been known to bind methylated histones, PWWP was shown to exhibit histone binding ability only until recently. The PWWP domain has been shown to be a DNA binding domain, but sequence analysis and previous structural studies show that the PWWP domain exhibits significant similarity to other 'Royal Family' members, implying that the PWWP domain has the potential to bind histones. In order to further explore the function of the PWWP domain, we used the protein family approach to determine the crystal structures of the PWWP domains from seven different human proteins. Our fluorescence polarization binding studies show that PWWP domains have weak histone binding ability, which is also confirmed by our NMR titration experiments. Furthermore, we determined the crystal structures of the BRPF1 PWWP domain in complex with H3K36me3, and HDGF2 PWWP domain in complex with H3K79me3 and H4K20me3. PWWP proteins constitute a new family of methyl lysine histone binders. The PWWP domain consists of three motifs: a canonical {beta}-barrel core, an insertion motif between the second and third {beta}-strands and a C-terminal {alpha}-helix bundle. Both the canonical {beta}-barrel core and the insertion motif are directly involved in histone binding. The PWWP domain has been previously shown to be a DNA binding domain. Therefore, the PWWP domain exhibits dual functions: binding both DNA and methyllysine histones.

  6. X-ray Crystallographic Studies of Substrate Binding to Aristolochene Synthase Suggest a Metal Ion Binding Sequence for Catalysis

    SciTech Connect (OSTI)

    Shishova,E.; Yu, F.; Miller, D.; Faraldos, J.; Zhao, Y.; Coates, R.; Allemann, R.; Cane, D.; Christianson, D.

    2008-01-01

    The universal sesquiterpene precursor, farnesyl diphosphate (FPP), is cyclized in an Mg2+-dependent reaction catalyzed by the tetrameric aristolochene synthase from Aspergillus terreus to form the bicyclic hydrocarbon aristolochene and a pyrophosphate anion (PPi) coproduct. The 2.1- Angstroms resolution crystal structure determined from crystals soaked with FPP reveals the binding of intact FPP to monomers A-C, and the binding of PPi and Mg2+B to monomer D. The 1.89- Angstroms resolution structure of the complex with 2-fluorofarnesyl diphosphate (2F-FPP) reveals 2F-FPP binding to all subunits of the tetramer, with Mg2+Baccompanying the binding of this analogue only in monomer D. All monomers adopt open activesite conformations in these complexes, but slight structural changes in monomers C and D of each complex reflect the very initial stages of a conformational transition to the closed state. Finally, the 2.4- Angstroms resolution structure of the complex with 12,13-difluorofarnesyl diphosphate (DF-FPP) reveals the binding of intact DF-FPP to monomers A-C in the open conformation and the binding of PPi, Mg2+B, and Mg2+C to monomer D in a predominantly closed conformation. Taken together, these structures provide 12 independent 'snapshots' of substrate or product complexes that suggest a possible sequence for metal ion binding and conformational changes required for catalysis.

  7. Cellulose Binding Protein from the Parasitic Nematode Heterodera schachtii Interacts with Arabidopsis Pectin

    E-Print Network [OSTI]

    Hussey, Richard S.

    Cellulose Binding Protein from the Parasitic Nematode Heterodera schachtii Interacts Heterodera glycines also produces a cellulose binding protein (Hg CBP) secretory protein. To determine

  8. Post-transcriptional coordination by an RNA-binding protein

    E-Print Network [OSTI]

    Wolf, Joshua Jaeger

    2010-01-01

    RNA-binding proteins can regulate the stability, localization, and translation of their target mRNAs. Post-transcriptional regulation can orchestrate dynamic changes in gene expression, and can coordinate multiple cellular ...

  9. Original article Distribution of endogenous retinoids, retinoid binding

    E-Print Network [OSTI]

    Paris-Sud XI, Universit de

    of specific retinoid-binding proteins was investigated; these are involved in vitamin A transport, metabolism is induced by a concentration gradient (high posteri- orly) of all-trans-RA along the anterior-p

  10. Metal binding proteins, recombinant host cells and methods

    DOE Patents [OSTI]

    Summers, Anne O.; Caguiat, Jonathan J.

    2004-06-15

    The present disclosure provides artificial heavy metal binding proteins termed chelons by the inventors. These chelons bind cadmium and/or mercuric ions with relatively high affinity. Also disclosed are coding sequences, recombinant DNA molecules and recombinant host cells comprising those recombinant DNA molecules for expression of the chelon proteins. In the recombinant host cells or transgenic plants, the chelons can be used to bind heavy metals taken up from contaminated soil, groundwater or irrigation water and to concentrate and sequester those ions. Recombinant enteric bacteria can be used within the gastrointestinal tracts of animals or humans exposed to toxic metal ions such as mercury and/or cadmium, where the chelon recombinantly expressed in chosen in accordance with the ion to be rededicated. Alternatively, the chelons can be immobilized to solid supports to bind and concentrate heavy metals from a contaminated aqueous medium including biological fluids.

  11. Linear Scaling of the Exciton Binding Energy versus the Band...

    Office of Scientific and Technical Information (OSTI)

    Linear Scaling of the Exciton Binding Energy versus the Band Gap of Two-Dimensional Materials This content will become publicly available on August 6, 2016 Prev Next Title:...

  12. Second-order susceptibility from a tight-binding Hamiltonian

    E-Print Network [OSTI]

    Dumitrica, T.; Graves, JS; Allen, Roland E.

    1998-01-01

    Using a new formalism that modifies a tight-binding Hamiltonian to include interaction with a time-dependent electromagnetic field, we have obtained an analytical expression for the second-order susceptibility. This expression has been used...

  13. MCM ring hexamerization is a prerequisite for DNA-binding

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Froelich, Clifford A.; Nourse, Amanda; Enemark, Eric J.

    2015-09-13

    The hexameric Minichromosome Maintenance (MCM) protein complex forms a ring that unwinds DNA at the replication fork in eukaryotes and archaea. Our recent crystal structure of an archaeal MCM N-terminal domain bound to single-stranded DNA (ssDNA) revealed ssDNA associating across tight subunit interfaces but not at the loose interfaces, indicating that DNA-binding is governed not only by the DNA-binding residues of the subunits (MCM ssDNA-binding motif, MSSB) but also by the relative orientation of the subunits. We now extend these findings to show that DNA-binding by the MCM N-terminal domain of the archaeal organism Pyrococcus furiosus occurs specifically in themorehexameric oligomeric form. We show that mutants defective for hexamerization are defective in binding ssDNA despite retaining all the residues observed to interact with ssDNA in the crystal structure. One mutation that exhibits severely defective hexamerization and ssDNA-binding is at a conserved phenylalanine that aligns with the mouse Mcm4(Chaos3) mutation associated with chromosomal instability, cancer, and decreased intersubunit association.less

  14. MANAGING TIGHT BINDING RECEPTORS FOR NEW SPEARATIONS TECHNOLOGIES

    SciTech Connect (OSTI)

    DARYLE H BUSCH RICHARD S GIVENS

    2004-12-10

    Much of the earth's pollution involves compounds of the metallic elements, including actinides, strontium, cesium, technetium, and RCRA metals. Metal ions bind to molecules called ligands, which are the molecular tools that can manipulate the metal ions under most conditions. This DOE-EMSP sponsored program strives (1) to provide the foundations for using the most powerful ligands in transformational separations technologies and (2) to produce seminal examples of their applications to separations appropriate to the DOE EM mission. These ultra tight-binding ligands can capture metal ions in the most competitive of circumstances (from mineralized sites, lesser ligands, and even extremely dilute solutions), but they react so slowly that they are useless in traditional separations methodologies. Two attacks on this problem are underway. The first accommodates to the challenging molecular lethargy by developing a seminal slow separations methodology termed the soil poultice. The second designs ligands that are only tight-binding while wrapped around the targeted metal ion, but can be put in place by switch-binding and removed by switch-release. We envision a kind of molecular switching process to accelerate the union between metal ion and tight-binding ligand. Molecular switching processes are suggested for overcoming the slow natural equilibration rate with which ultra tight-binding ligands combine with metal ions. Ligands that bind relatively weakly combine with metal ions rapidly, so the trick is to convert a ligand from a weak, rapidly binding species to a powerful, slow releasing ligand--during the binding of the ligand to the metal ion. Such switch-binding ligands must react with themselves, and the reaction must take place under the influence of the metal ion. For example, our generation 1 ligands showed that a well-designed linear ligand with ends that readily combine, forms a cyclic molecule when it wraps around a metal ion. Our generation 2 ligands are even more interesting. They convert from rings to structures that wrap around a metal ion to form a cage. These ligands are called cryptands. Switch release is accomplished by photolytic cleavage of a bond to convert a cyclic ligand into a linear ligand or to break similar bonds in a cryptate. Our studies have demonstrated switch binding and switch release with cryptates of calcium. These remarkable cyclic ligands and cage-like ligands are indeed tight-binding and may, in principle, be incorporated in various separations methodologies, including the soil poultice. The soil poultice mimics the way in which microbes secrete extremely powerful ligands into the soil in order to harvest iron. The cellular membrane of the microbe recognizes the iron/ligand complex and admits it into the cell. The soil poultice uses molecularly imprinted polymers (MIPs) to play the role of the cellular membrane. Imprinting involves creation of the polymer in the presence of the metal/ligand complex. In principle, a well design ligand/MIP combination can be highly selective toward almost any targeted metal ion. The principles for that design are the focus of these investigations. An imprinting molecule can interact with the polymer through any, some, or all of the so-called supramolecular modes; e.g., hydrogen bonding, electrostatic charge, minor ligand bonding, Pi-Pi stacking, and hydrophobic and van der Waals interactions. Historically these modes of binding have given MIPs only small re-binding capacities and very limited selectivities. This program has shown that each mode of interaction can be made more powerful than previously suspected and that combinations of different supramolecular interaction modes can produce remarkable synergisms. The results of this systematic study provide a firm foundation for tailoring molecular imprinted polymers for reclamation of specific metal ion, including those important to the DOE EM mission.

  15. Acid Gas Capture Using CO2-Binding Organic Liquids

    SciTech Connect (OSTI)

    Heldebrant, David J.; Koech, Phillip K.; Rainbolt, James E.; Zheng, Feng

    2010-11-10

    Current chemical CO2 scrubbing technology is primarily aqueous alkanolamine based. These systems rapidly bind CO2 (forming water-soluble carbamate and bicarbonate salts) however, the process has serious disadvantages. The concentration of monoethanolamine rarely exceeds 30 wt % due to the corrosive nature of the solution, and this reduces the maximum CO2 volumetric (?108 g/L) and gravimetric capacity (?7 wt%) of the CO2 scrubber. The ?30 wt % loading of ethanolamine also means that a large excess of water must be pumped and heated during CO2 capture and release, and this greatly increases the energy requirements especially considering the high specific heat of water (4 j/g-1K-1). Our approach is to switch to organic systems that chemically bind CO2 as liquid alkylcarbonate salts. Our CO2-binding organic liquids have higher CO2 solubility, lower specific heats, potential for less corrosion and lower binding energies for CO2 than aqueous systems. CO2BOLs also reversibly bind and release mixed sulfur oxides. Furthermore the CO2BOL system can be direct solvent replacements for any solvent based CO2 capture systems because they are commercially available reagents and because they are fluids they would not require extensive process re-engineering.

  16. Dynamic Structural Rearrangements Between DNA Binding Modes of E. coli SSB Protein

    E-Print Network [OSTI]

    Lohman, Timothy M.

    an oligonucleotide/oligosaccharide bind- ing (OB) fold,5,79 hence the tetramer has four po- tential ssDNA binding sites. The SSB tetramer can bind long ssDNA in a variety of binding modes depending on solutionCl) and high protein to DNA ratios, an SSB tetramer binds to ssDNA with high inter-tetramer cooperativity using

  17. The Cellulose-binding Domains from Cellulomonas fimi bbb-1,4-Glucanase CenC Bind Nitroxide Spin-labeled

    E-Print Network [OSTI]

    McIntosh, Lawrence P.

    The Cellulose-binding Domains from Cellulomonas fimi bbb-1,4-Glucanase CenC Bind Nitroxide Spin6T 1Z3, Canada The N-terminal cellulose-binding domains CBDN1 and CBDN2 from Cellulomonas mi cellulase CenC each adopt a jelly-roll b-sandwich struc- ture with a cleft into which amorphous cellulose

  18. Orientation-dependent binding energy of graphene on palladium

    SciTech Connect (OSTI)

    Kappes, Branden B.; Ebnonnasir, Abbas; Ciobanu, Cristian V. [Department of Mechanical Engineering and Materials Science Program, Colorado School of Mines, Golden, Colorado 80401 (United States)] [Department of Mechanical Engineering and Materials Science Program, Colorado School of Mines, Golden, Colorado 80401 (United States); Kodambaka, Suneel [Department of Materials Science and Engineering, University of California, Los Angeles, Los Angeles, California 90095 (United States)] [Department of Materials Science and Engineering, University of California, Los Angeles, Los Angeles, California 90095 (United States)

    2013-02-04

    Using density functional theory calculations, we show that the binding strength of a graphene monolayer on Pd(111) can vary between physisorption and chemisorption depending on its orientation. By studying the interfacial charge transfer, we have identified a specific four-atom carbon cluster that is responsible for the local bonding of graphene to Pd(111). The areal density of such clusters varies with the in-plane orientation of graphene, causing the binding energy to change accordingly. Similar investigations can also apply to other metal substrates and suggests that physical, chemical, and mechanical properties of graphene may be controlled by changing its orientation.

  19. Molecular Cell High-Affinity Binding of Chp1 Chromodomain

    E-Print Network [OSTI]

    Halazonetis, Thanos

    Molecular Cell Article High-Affinity Binding of Chp1 Chromodomain to K9 Methylated Histone H3, Chp1, and siRNAs derived from centro- meric repeats. Recruitment of RITS to centromeres has been establishment. Our crystal structure of Chp1's chromodomain in complex with a trimethylated lysine 9 H3 peptide

  20. Telomeres and telomere binding proteins in Arabidopsis thaliana

    E-Print Network [OSTI]

    Shakirov, Yevgeniy Vitalievich

    2004-09-30

    . Additionally, two Arabidopsis genes, AtPot1 and AtPot2, were identified and characterized. The genes encode two single-strand telomeric DNA binding proteins. AtPot1 and AtPot2 proteins can homo- and heterodimerize in vitro. Pot1 protein predominantly localizes...

  1. CAR2 Displays Unique Ligand Binding and RXR Heterodimerization Characteristics

    E-Print Network [OSTI]

    Omiecinski, Curtis

    CAR2 Displays Unique Ligand Binding and RXR Heterodimerization Characteristics Scott S. Auerbach ABSTRACT: The constitutive androstane receptor (CAR; NR1I3) regulates the expression of genes involved in xenobiotic metabolism. Alternative splicing of the human CAR gene yields an array of mRNAs that encode

  2. Binding of Harvested Bacterial Exopolymers to the Surface of

    E-Print Network [OSTI]

    of the EPS showed that binding strength to calcite depended on the chemical nature of the polymer. Introduction Dissolution of calcium carbonate (calcite) affects global carbon cycling (1), the chemistry of calcium carbonate in the form of limestone or marble. Retardation of deterioration is important

  3. A probabilistic approach to microRNA-target binding

    SciTech Connect (OSTI)

    Ogul, Hasan; Umu, Sinan U.; Bioinformatics Program, Informatics Institute, Middle East Technical University, Cankaya TR-06800, Ankara ; Tuncel, Y. Yener; Akkaya, Mahinur S.

    2011-09-16

    Highlights: {yields} A new probabilistic model is introduced for microRNA-target binding. {yields} The new model significantly outperforms RNAHybrid and miRTif. {yields} The experiments can unveil the effects of the type and directions of distinct base pairings. -- Abstract: Elucidation of microRNA activity is a crucial step in understanding gene regulation. One key problem in this effort is how to model the pairwise interactions of microRNAs with their targets. As this interaction is strongly mediated by their sequences, it is desired to set-up a probabilistic model to explain the binding preferences between a microRNA sequence and the sequence of a putative target. To this end, we introduce a new model of microRNA-target binding, which transforms an aligned duplex to a new sequence and defines the likelihood of this sequence using a Variable Length Markov Chain. It offers a complementary representation of microRNA-mRNA pairs for microRNA target prediction tools or other probabilistic frameworks of integrative gene regulation analysis. The performance of present model is evaluated by its ability to predict microRNA-target mRNA interaction given a mature microRNA sequence and a putative mRNA binding site. In regard to classification accuracy, it outperforms two recent methods based on thermodynamic stability and sequence complementarity. The experiments can also unveil the effects of base pairing types and non-seed region in duplex formation.

  4. Expression and subcellular localisation of poly(A)-binding proteins

    E-Print Network [OSTI]

    Burgess, Hannah

    2010-11-24

    Poly(A)-binding proteins (PABPs) are important regulators of mRNA translation and stability. In mammals four cytoplasmic PABPs with a similar domain structure have been described - PABP1, tPABP, PABP4 and ePABP. The ...

  5. Compilation as Metacomputation: Binding Time Separation in Modular Compilers

    E-Print Network [OSTI]

    Kamin, Sam

    Compilation as Metacomputation: Binding Time Separation in Modular Compilers (Extended Abstract ings. Metacomputationstyle specification lends itself to semanticsdirected compilation, which we demonstrate by creating a modular compiler for a higherorder, imperative, Algollike language. Keywords

  6. Methods of use of cellulose binding domain proteins

    DOE Patents [OSTI]

    Shoseyov, O.; Shpiegl, I.; Goldstein, M.A.; Doi, R.H.

    1997-09-23

    A cellulose binding domain (CBD) having a high affinity for crystalline cellulose and chitin is disclosed, along with methods for the molecular cloning and recombinant production. Fusion products comprising the CBD and a second protein are likewise described. A wide range of applications are contemplated for both the CBD and the fusion products, including drug delivery, affinity separations, and diagnostic techniques. 16 figs.

  7. Workshop on gate valve pressure locking and thermal binding

    SciTech Connect (OSTI)

    Brown, E.J.

    1995-07-01

    The purpose of the Workshop on Gate Valve Pressure Locking and Thermal Binding was to discuss pressure locking and thermal binding issues that could lead to inoperable gate valves in both boiling water and pressurized water reactors. The goal was to foster exchange of information to develop the technical bases to understand the phenomena, identify the components that are susceptible, discuss actual events, discuss the safety significance, and illustrate known corrective actions that can prevent or limit the occurrence of pressure locking or thermal binding. The presentations were structured to cover U.S. Nuclear Regulatory Commission staff evaluation of operating experience and planned regulatory activity; industry discussions of specific events, including foreign experience, and efforts to determine causes and alleviate the affects; and valve vendor experience and recommended corrective action. The discussions indicated that identifying valves susceptible to pressure locking and thermal binding was a complex process involving knowledge of components, systems, and plant operations. The corrective action options are varied and straightforward.

  8. Host Cell Responses Induced by Hepatitis C Virus Binding

    E-Print Network [OSTI]

    Timmer, Jens

    Host Cell Responses Induced by Hepatitis C Virus Binding Xinhua Fang,1 Mirjam B. Zeisel,1 Jochen. Blum,1 and Thomas F. Baumert1,5 Initiation of hepatitis C virus (HCV) infection is mediated by docking nitiation of hepatitis C virus (HCV) infection is me- diated by docking of the viral envelope to the hepa

  9. Inhibition Of Call-Cell Binding By Kipid Assemblies

    DOE Patents [OSTI]

    Nagy, Jon O. (Rodeo, CA), Bargatze, Robert F. (Bozeman, MT)

    2003-12-16

    This invention relates generally to the field of therapeutic compounds designed to interfere between the binding of ligands and their receptors on cell surface. More specifically, it provides products and methods for inhibiting cell migration and activation using lipid assemblies with surface recognition elements that are specific for the receptors involved in cell migration and activation.

  10. Inhibition of cell-cell binding by lipid assemblies

    DOE Patents [OSTI]

    Nagy, Jon O. (Rodeo, CA); Bargatze, Robert F. (Bozeman, MT)

    2001-05-22

    This invention relates generally to the field of therapeutic compounds designed to interfere between the binding of ligands and their receptors on cell surface. More specifically, it provides products and methods for inhibiting cell migration and activation using lipid assemblies with surface recognition elements that are specific for the receptors involved in cell migration and activation.

  11. Automatic Generation of Tcl Bindings for C and C++ Libraries

    E-Print Network [OSTI]

    Heidrich, Wolfgang

    functions. This facility has been used to create a variety of language bindings for C libraries, ranging++ library functions to Tcl, is that they do not normally receive their arguments using this argc public member function, but since C(++) data can not be addressed directly from Tcl, string handles need

  12. Analysis of the Vertebrate Insulator Protein CTCF-Binding

    E-Print Network [OSTI]

    D. Green,4 Michael Q. Zhang,3 Victor V. Lobanenkov,2 and Bing Ren1, * 1 Ludwig Institute for Cancer by preventing the spread of heterochromatin and restricting transcriptional enhancers from acti- vation ex- pressed nuclear protein with 11-zinc finger (ZF) DNA- binding domain (Filippova et al., 1996

  13. The peanut lectin-binding glycoproteins of human epidermal keratinocytes

    SciTech Connect (OSTI)

    Morrison, A.I. (Max-Planck-Institute fuer Systemphysiologie, Dortmund (West Germany)); Keeble, S.; Watt, F.M. (Imperial Cancer Research Fund, London (England))

    1988-08-01

    The peanut lectin (PNA) is known to bind more strongly to keratinocytes that are undergoing terminal differentiation than to proliferating keratinocytes. In order to investigate the significance of this change in cell-surface carbohydrate authors have identified the PNA-binding glycoproteins of cultured human keratinocytes and antibodies against them. Two heavily glycosylated bands of 110 and 250 kDa were resolved by PAGE of ({sup 14}C)galactose- or ({sup 14}C)mannose- and ({sup 14}C)glucosamine-labeled cell extracts eluted with galactose from PNA affinity columns. The higher molecular weight band was also detected on PNA blots of unlabeled cell extracts transferred to nitrocellulose. Both bands were sensitive to pronase digestion, but only the 250-kDa band was digested with trypsin. A rabbit antiserum that we prepared (anti-PNA-gp) immunoprecipitated both bands from cell extracts. In contrast to PNA, anti-PNA-gp bound equally to proliferating and terminally differentiating cells, indicating that some epitope(s) of the PNA-binding glycoproteins is present on the cell surface prior to terminal differentiation. When keratinocytes grown as a monolayer in low-calcium medium were switched to medium containing 2 mM calcium ions in order to induce desmosome formation and stratification, there was a dramatic redistribution of the PNA-binding glycoproteins, which became concentrated at the boundaries between cells. This may suggest a role for the glycoproteins in cell-cell interactions during stratification.

  14. Methods of detection using a cellulose binding domain fusion product

    DOE Patents [OSTI]

    Shoseyov, Oded (Shimshon, IL); Shpiegl, Itai (North Gallilea, IL); Goldstein, Marc A. (Davis, CA); Doi, Roy H. (Davis, CA)

    1999-01-01

    A cellulose binding domain (CBD) having a high affinity for crystalline cellulose and chitin is disclosed, along with methods for the molecular cloning and recombinant production thereof. Fusion products comprising the CBD and a second protein are likewise described. A wide range of applications are contemplated for both the CBD and the fusion products, including drug delivery, affinity separations, and diagnostic techniques.

  15. Methods of use of cellulose binding domain proteins

    DOE Patents [OSTI]

    Shoseyov, Oded (Karmey Yosef, IL); Shpiegl, Itai (Rehovot, IL); Goldstein, Marc A. (Davis, CA); Doi, Roy H. (Davis, CA)

    1997-01-01

    A cellulose binding domain (CBD) having a high affinity for crystalline cellulose and chitin is disclosed, along with methods for the molecular cloning and recombinant production thereof. Fusion products comprising the CBD and a second protein are likewise described. A wide range of applications are contemplated for both the CBD and the fusion products, including drug delivery, affinity separations, and diagnostic techniques.

  16. Methods of detection using a cellulose binding domain fusion product

    DOE Patents [OSTI]

    Shoseyov, O.; Shpiegl, I.; Goldstein, M.A.; Doi, R.H.

    1999-01-05

    A cellulose binding domain (CBD) having a high affinity for crystalline cellulose and chitin is disclosed, along with methods for the molecular cloning and recombinant production. Fusion products comprising the CBD and a second protein are likewise described. A wide range of applications are contemplated for both the CBD and the fusion products, including drug delivery, affinity separations, and diagnostic techniques. 34 figs.

  17. Glucose oxidation in heart-type fatty acid binding protein null mice

    E-Print Network [OSTI]

    Adhikari, Sean

    2006-10-30

    Heart-type fatty acid binding protein (H-FABP) is a major fatty acid binding factor in skeletal muscles. Genetic lack of H-FABP severely impairs the esterification and oxidation of exogenous fatty acids in soleus muscles ...

  18. Insight into Ligand Diversity and Novel Biological Roles for Family 32 Carbohydrate-Binding Modules

    E-Print Network [OSTI]

    Eirin Lopez, Jose Maria

    a new platform for the prediction of CBM binding specificity and highlight significant new targets et al. 2007). For example, Yersinia enterocolitica contains a family 32 car- bohydrate-binding module

  19. Expression and characterisation of a novel poly(A)-binding protein, PABP5

    E-Print Network [OSTI]

    Anderson, Ross Calley

    2010-11-24

    The poly(A)-binding proteins (PABPs) are a family of eukaryotic RNA-binding proteins with key roles in mRNA translation and stability. The molecular function of PABPs have been largely revealed through study of the ...

  20. Common binding by redundant group B Sox proteins is evolutionarily conserved in Drosophila.

    E-Print Network [OSTI]

    Carl, Sarah H.; Russell, Steven

    2015-04-13

    Three-way comparison of Dichaete binding. (A) Pie chart showin present in one species (47%), two species (23%) or all three species (30%). in D. melanogaster, D. simulans and D. yakuba clustered by binding affinity key and histogram shows...

  1. Syntax-driven bindings of Spanish clitic pronoun Ivan V. Meza Ruiz

    E-Print Network [OSTI]

    Pineda, Luis

    on con la teoria de binding. Los pronombres cliticos del espa~nol presentan un comportamiento dual dado control de objeto. Palabras clave: Pronombres cliticos, Teoria de Binding, Reflexividad, HPSG Abstract

  2. Discovery and Characterization of a Cell-Permeable, Small-Molecule c-Abl Kinase Activator that Binds to the Myristoyl Binding Site

    SciTech Connect (OSTI)

    Yang, Jingsong; Campobasso, Nino; Biju, Mangatt P.; Fisher, Kelly; Pan, Xiao-Qing; Cottom, Josh; Galbraith, Sarah; Ho, Thau; Zhang, Hong; Hong, Xuan; Ward, Paris; Hofmann, Glenn; Siegfried, Brett; Zappacosta, Francesca; Washio, Yoshiaki; Cao, Ping; Qu, Junya; Bertrand, Sophie; Wang, Da-Yuan; Head, Martha S.; Li, Hu; Moores, Sheri; Lai, Zhihong; Johanson, Kyung; Burton, George; Erickson-Miller, Connie; Simpson, Graham; Tummino, Peter; Copeland, Robert A.; Oliff, Allen

    2014-10-02

    c-Abl kinase activity is regulated by a unique mechanism involving the formation of an autoinhibited conformation in which the N-terminal myristoyl group binds intramolecularly to the myristoyl binding site on the kinase domain and induces the bending of the {alpha}I helix that creates a docking surface for the SH2 domain. Here, we report a small-molecule c-Abl activator, DPH, that displays potent enzymatic and cellular activity in stimulating c-Abl activation. Structural analyses indicate that DPH binds to the myristoyl binding site and prevents the formation of the bent conformation of the {alpha}I helix through steric hindrance, a mode of action distinct from the previously identified allosteric c-Abl inhibitor, GNF-2, that also binds to the myristoyl binding site. DPH represents the first cell-permeable, small-molecule tool compound for c-Abl activation.

  3. The role of cooperative binding on noise expression

    E-Print Network [OSTI]

    P. S. Gutierrez; D. Monteoliva; L. Diambra

    2009-08-02

    The origin of stochastic fluctuations in gene expression has received considerable attention recently. Fluctuations in gene expression are particularly pronounced in cellular systems because of the small copy number of species undergoing transitions between discrete chemical states and the small size of biological compartments. In this paper, we propose a stochastic model for gene expression regulation including several binding sites, considering elementary reactions only. The model is used to investigate the role of cooperativity on the intrinsic fluctuations of gene expression, by means of master equation formalism. We found that the Hill coefficient and the level of noise increases as the interaction energy between activators increases. Additionally, we show that the model allows to distinguish between two cooperative binding mechanisms.

  4. Improved value for the silicon free exciton binding energy

    SciTech Connect (OSTI)

    Green, Martin A., E-mail: m.green@unsw.edu.au [Australian Centre for Advanced Photovoltaics, School of Photovoltaic and Renewable Energy Engineering, University of New South Wales, Sydney, Australia 2052 (Australia)

    2013-11-15

    The free exciton binding energy is a key parameter in silicon material and device physics. In particular, it provides the necessary link between the energy threshold for valence to conduction band optical absorption and the bandgap determining electronic properties. The long accepted low temperature binding energy value of 14.7 0.4 meV is reassessed taking advantage of developments subsequent to its original determination, leading to the conclusion that this value is definitely an underestimate. Using three largely independent experimental data sets, an improved low temperature value of 15.01 0.06 meV is deduced, in good agreement with the most comprehensive theoretical calculations to date.

  5. Syntheses and DNA binding of new cationic porphyrintetrapeptide conjugates Gbor Mez a

    E-Print Network [OSTI]

    Langowski, Jrg

    shifts and hypochromicities. Decomposition of absorption spectra suggested the formation of two of di- and tricationic porphyrins bind to DNA by two distinct binding modes which can be identi ed agents [6,7]. The binding of cationic porphyrin derivatives to nucleic acids has been the subject

  6. Promiscuous binding of extracellular peptides to cell surface class I MHC protein

    E-Print Network [OSTI]

    Eisen, Herman N.

    Algorithms derived from measurements of short-peptide (810 mers) binding to class I MHC proteins suggest that the binding groove of a class I MHC protein, such as K[superscript b], can bind well over 1 million different ...

  7. SFmap: a web server for motif analysis and prediction of splicing factor binding sites

    E-Print Network [OSTI]

    Mandel-Gutfreund, Yael

    SFmap: a web server for motif analysis and prediction of splicing factor binding sites Inbal Paz1) that bind to sequence elements on the RNA. SFmap is a web server for predicting putative SF binding sites by the user. SFmap results are provided both as a text file and as a graphical web interface. INTRODUCTION

  8. Ultrastrong Optical Binding of Metallic Nanoparticles Vassili Demergis and Ernst-Ludwig Florin*

    E-Print Network [OSTI]

    Texas at Austin. University of

    Ultrastrong Optical Binding of Metallic Nanoparticles Vassili Demergis and Ernst-Ludwig Florin the optical binding force, which has been assumed to be weak compared to the optical gradient and scattering forces. We show that trapping by the optical binding force can be over 20 times stronger than

  9. Theory of Free Energy and Entropy in Noncovalent Binding Huan-Xiang Zhou*,

    E-Print Network [OSTI]

    Weston, Ken

    Theory of Free Energy and Entropy in Noncovalent Binding Huan-Xiang Zhou*, and Michael K. Gilson, Rockville, Maryland 20850 Received December 23, 2008 Contents 1. Introduction 4092 2. Free Energy, Partition.4. Solvation and a Temperature-Dependent Energy Function 4096 3. Binding Free Energy and Binding Constant 4096

  10. Metal binding in proteins: machine learning complements X-ray absorption spectroscopy

    E-Print Network [OSTI]

    Passerini, Andrea

    Metal binding in proteins: machine learning complements X-ray absorption spectroscopy Marco Lippi1 for the identification of metalloproteins and metal binding sites on a genome scale. An extensive evaluation conducted in combination with X- ray absorption spectroscopy shows the great potentiality of the approach. 1 Metal binding

  11. Efficient Evaluation of Binding Free Energy Using Continuum Electrostatics Danzhi Huang and Amedeo Caflisch*

    E-Print Network [OSTI]

    Caflisch, Amedeo

    Efficient Evaluation of Binding Free Energy Using Continuum Electrostatics Solvation Danzhi Huang of the absolute free energy of binding. A predictive accuracy of about 1.0 kcal/mol is obtained for 13 and 29 into proteins of known structure require fast and accurate methods for the evaluation of binding free energies.1

  12. Non-binding of Flavor-Singlet Hadrons to Nuclei

    E-Print Network [OSTI]

    Glennys R. Farrar; Gabrijela Zaharijas

    2003-02-20

    Strongly attractive color forces in the flavor singlet channel may lead to a stable H dibaryon. Here we show that an H or other compact, flavor singlet hadron is unlikely to bind to nuclei, so that bounds on exotic isotopes do not exclude their stability. Remarkably, a stable H appears to evade other experimental constraints as well, when account is taken of its expected compact spatial wavefunction.

  13. Reversible Acid Gas Capture Using CO2-Binding Organic Liquids

    SciTech Connect (OSTI)

    Heldebrant, David J.; Koech, Phillip K.; Yonker, Clement R.; Rainbolt, James E.; Zheng, Feng

    2010-08-31

    Acid gas scrubbing technology is predominantly aqueous alkanolamine based. Of the acid gases, CO2, H2S and SO2 have been shown to be reversible, however there are serious disadvantages with corrosion and high regeneration costs. The primary scrubbing system composed of monoethanolamine is limited to 30% by weight because of the highly corrosive solution. This gravimetric limitation limits the CO2 volumetric (?108 g/L) and gravimetric capacity (?7 wt%) of the system. Furthermore the scrubbing system has a large energy penalty from pumping and heating the excess water required to dissolve the MEA bicarbonate salt. Considering the high specific heat of water (4 j/g-1K-1), low capacities and the high corrosion we set out to design a fully organic solvent that can chemically bind all acid gases i.e. CO2 as reversible alkylcarbonate ionic liquids or analogues thereof. Having a liquid acid gas carrier improves process economics because there is no need for excess solvent to pump and to heat. We have demonstrated illustrated in Figure 1, that CO2-binding organic liquids (CO2BOLs) have a high CO2 solubility paired with a much lower specific heat (<1.5 J/g-1K-1) than aqueous systems. CO2BOLs are a subsection of a larger class of materials known as Binding Organic Liquids (BOLs). Our BOLs have been shown to reversibly bind and release COS, CS2, and SO2, which we denote COSBOLS, CS2BOLs and SO2BOLs. Our BOLs are highly tunable and can be designed for post or pre-combustion gas capture. The design and testing of the next generation zwitterionic CO2BOLs and SO2BOLs are presented.

  14. Synthesis and Characterization of Polyamine Bicycles for Anion Binding

    E-Print Network [OSTI]

    Morehouse, Paula Kay

    2007-10-09

    ,4,12,15,18,26,31,39-octaazapentacyclo [13.13.13.1.6,101.20,241.33,37] tetratetraconta-6, 7,9,20(43), 21,23,33(42),34,36-nonaene], N(CH2CH2NHCH2-m-xylyl-CH2NHCH2CH2)3N), 12, is readily capable of being protonated at the bridgehead amines. As a result it is also capable of binding anions...

  15. High molecular weight polysaccharide that binds and inhibits virus

    DOE Patents [OSTI]

    Konowalchuk, Thomas W

    2014-01-14

    This invention provides a high molecular weight polysaccharide capable of binding to and inhibiting virus and related pharmaceutical formulations and methods on inhibiting viral infectivity and/or pathogenicity, as well as immunogenic compositions. The invention further methods of inhibiting the growth of cancer cells and of ameliorating a symptom of aging. Additionally, the invention provides methods of detecting and/or quantifying and/or isolating viruses.

  16. Bounds to binding energies from the concavity of thermodynamical functions

    E-Print Network [OSTI]

    B. K. Jennings; B. R. Barrett; B. G. Giraud

    2007-08-22

    Sequences of experimental ground-state energies are mapped onto concave patterns cured from convexities due to pairing and/or shell effects. The same patterns, completed by a list of excitation energies, can be used to give numerical estimates of the grand potential $\\Omega(\\beta,\\mu)$ for a mixture of nuclei at low or moderate temperatures $T=\\beta^{-1}$ and at many chemical potentials $\\mu.$ The average nucleon number $(\\beta,\\mu)$ then becomes a continuous variable, allowing extrapolations towards nuclear masses closer to drip lines. We study the possible concavity of several thermodynamical functions, such as the free energy and the average energy, as functions of $.$ Concavity, when present in such functions, allows trivial interpolations and extrapolations providing upper and lower bounds, respectively, to binding energies. Such bounds define an error bar for the prediction of binding energies. An extrapolation scheme for such concave functions is tested. We conclude with numerical estimates of the binding energies of a few nuclei closer to drip lines.

  17. Binding energy of the $X(3872)$ at unphysical pion masses

    E-Print Network [OSTI]

    Baru, V; Filin, A A; Gegelia, J; Nefediev, A V

    2015-01-01

    Chiral extrapolation of the $X(3872)$ binding energy is investigated using the modified Weinberg formulation of chiral effective field theory for the $D \\bar{D}^*$ scattering. Given its explicit renormalisability, this approach is particularly useful to explore the interplay of the long- and short-range $D \\bar{D}^*$ forces in the $X(3872)$ from studying the light-quark (pion) mass dependence of its binding energy. In particular, the parameter-free leading-order calculation shows that the $X$-pole disappears for unphysical large pion masses. On the other hand, without contradicting the naive dimensional analysis, the higher-order pion-mass-dependent contact interaction can change the slope of the binding energy at the physical point yielding the opposite scenario of a stronger bound $X$ at pion masses larger than its physical value. An important role of the pion dynamics and of the 3-body $D\\bar{D}\\pi$ effects for chiral extrapolations of the $X$-pole is emphasised. The results of the present study should be ...

  18. Gold Binding by Native and Chemically Modified Hops Biomasses

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Lpez, M. Laura; Gardea-Torresdey, J. L.; Peralta-Videa, J. R.; de la Rosa, G.; Armendriz, V.; Herrera, I.; Troiani, H.; Henning, J.

    2005-01-01

    Heavy metals from mining, smelting operations and other industrial processing facilities pollute wastewaters worldwide. Extraction of metals from industrial effluents has been widely studied due to the economic advantages and the relative ease of technical implementation. Consequently, the search for new and improved methodologies for the recovery of gold has increased. In this particular research, the use of cone hops biomass ( Humulus lupulus ) was investigated as a new option for gold recovery. The results showed that the gold binding to native hops biomass was pH dependent from pH 2 to pH 6, with a maximum percentage bindingmoreat pH 3. Time dependency studies demonstrated that Au(III) binding to native and modified cone hops biomasses was found to be time independent at pH 2 while at pH 5, it was time dependent. Capacity experiments demonstrated that at pH 2, esterified hops biomass bound 33.4 mg Au/g of biomass, while native and hydrolyzed hops biomasses bound 28.2 and 12.0 mg Au/g of biomass, respectively. However, at pH 5 the binding capacities were 38.9, 37.8 and 11.4 mg of Au per gram of native, esterified and hydrolyzed hops biomasses, respectively. less

  19. Sex Hormones Genotypes and Phenotypes and Determinants of Sex Hormone Binding Globulin in relation to Type 2 Diabetes Risk

    E-Print Network [OSTI]

    GOTO, ATSUSHI

    2012-01-01

    Consumption in Relation to Sex HormoneBinding Globulin andin Relation to Circulating Sex Hormone-binding GlobulinReferences 4. Genes in Sex Hormone Pathways and Diabetes

  20. Using ISC & GIS to predict sulfur deposition from coal-fired power plants

    E-Print Network [OSTI]

    Lopez, Jose Ignacio

    1993-01-01

    The goal of this research project was to determine if atmospheric sources have the potential of contributing significantly to the sulfur content of grazed forage. Sulfur deposition resulting from sulfur dioxide emissions from coal- fired power...

  1. Integrated Support Center (ISC) Homepage | U.S. DOE Office of Science (SC)

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    AFDC Printable Version Share this resource Send a link to EERE: Alternative Fuels Data Center Home Page to someone by E-mail Share EERE: Alternative Fuels Data Center Home Page on Facebook Tweet about EERE: Alternative Fuels Data Center Home Page on Twitter Bookmark EERE: Alternative Fuels Data Center Homesum_a_epg0_fpd_mmcf_m.xls" ,"Available from WebQuantity ofkandz-cm11 Outreach Home Room NewsInformation CurrentHenryInhibiting Individual NotchInspiringAppendixRadiationHome

  2. ISC-Chicago Office Categorical Exclusion (CX) Determinations | U.S. DOE

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    AFDC Printable Version Share this resource Send a link to EERE: Alternative Fuels Data Center Home Page to someone by E-mail Share EERE: Alternative Fuels Data Center Home Page on Facebook Tweet about EERE: Alternative Fuels Data Center Home Page on Twitter Bookmark EERE: Alternative Fuels Data Center Homesum_a_epg0_fpd_mmcf_m.xls" ,"Available from WebQuantityBonneville Power Administration would likeUniverse (JournalvivoHighHussein KhalilResearch88 Sign In About | CareersOffice of

  3. ISC-Oak Ridge Office Categorical Exclusion (CX) Determinations | U.S. DOE

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    AFDC Printable Version Share this resource Send a link to EERE: Alternative Fuels Data Center Home Page to someone by E-mail Share EERE: Alternative Fuels Data Center Home Page on Facebook Tweet about EERE: Alternative Fuels Data Center Home Page on Twitter Bookmark EERE: Alternative Fuels Data Center Homesum_a_epg0_fpd_mmcf_m.xls" ,"Available from WebQuantityBonneville Power Administration would likeUniverse (JournalvivoHighHussein KhalilResearch88 Sign In About | CareersOfficeOffice

  4. ISC15 The Road to Application Performance on Intel Xeon Phi

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    AFDC Printable Version Share this resource Send a link to EERE: Alternative Fuels Data Center Home Page to someone by E-mail Share EERE: Alternative Fuels Data Center Home Page on Facebook Tweet about EERE: Alternative Fuels Data Center Home Page on Twitter Bookmark EERE: Alternative Fuels Data Center Homesum_a_epg0_fpd_mmcf_m.xls" ,"Available from WebQuantityBonneville Power Administration would likeUniverse (JournalvivoHighHussein KhalilResearch88 Sign In About | Workshop for Intel®

  5. DNA-Binding Mechanism in Prokaryotic Partition Complex Formation

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    AFDC Printable Version Share this resource Send a link to EERE: Alternative Fuels Data Center Home Page to someone by E-mail Share EERE: Alternative Fuels Data Center Home Page on Facebook Tweet about EERE: Alternative Fuels Data Center Home Page on Twitter Bookmark EERE: Alternative Fuels Data Center Homesum_a_epg0_fpd_mmcf_m.xls" ,"Available from WebQuantityBonneville Power Administration would like submit theCovalent Bonding Low-Cost Ground8 GasDEVELOPMENTS E P I IT h itDNA-Binding

  6. Vibrational Softening of a Protein on Ligand Binding

    SciTech Connect (OSTI)

    Balog, Erica [Semmelweis University, Budapest, Hungary; Perahia, David [Ecole Normale Superieure de Cachan, Cachan, France; Smith, Jeremy C [ORNL; Merzel, Franci [National Institute of Chemistry, Solvenia

    2011-01-01

    Neutron scattering experiments have demonstrated that binding of the cancer drug methotrexate softens the low-frequency vibrations of its target protein, dihydrofolate reductase (DHFR). Here, this softening is fully reproduced using atomic detail normal-mode analysis. Decomposition of the vibrational density of states demonstrates that the largest contributions arise from structural elements of DHFR critical to stability and function. Mode-projection analysis reveals an increase of the breathing-like character of the affected vibrational modes consistent with the experimentally observed increased adiabatic compressibility of the protein on complexation.

  7. Towards engineering hormone-binding globulins as drug delivery agents

    E-Print Network [OSTI]

    Chan, Wee Lee; Zhou, Aiwu; Read, Randy J.

    2014-11-26

    (2014) Towards Engineering Hormone-Binding Globulins as Drug Delivery Agents. PLoS ONE 9(11): e113402. doi:10.1371/journal.pone. 0113402 Editor: Ashley M. Buckle, Monash University, Australia Received: June 10, 2014 Accepted: October 24, 2014 Published... stock solution was prepared by dissolving lyophilised cortisol (Sigma Aldrich) in 80% ethanol to make a 500 mM solution, which was then diluted with water to make solutions of 20, 40 and 80 mM, with water being used as a negative control. Aliquots...

  8. Hydroxyapatite-binding peptides for bone growth and inhibition

    DOE Patents [OSTI]

    Bertozzi, Carolyn R. (Berkeley, CA); Song, Jie (Shrewsbury, MA); Lee, Seung-Wuk (Walnut Creek, CA)

    2011-09-20

    Hydroxyapatite (HA)-binding peptides are selected using combinatorial phage library display. Pseudo-repetitive consensus amino acid sequences possessing periodic hydroxyl side chains in every two or three amino acid sequences are obtained. These sequences resemble the (Gly-Pro-Hyp).sub.x repeat of human type I collagen, a major component of extracellular matrices of natural bone. A consistent presence of basic amino acid residues is also observed. The peptides are synthesized by the solid-phase synthetic method and then used for template-driven HA-mineralization. Microscopy reveal that the peptides template the growth of polycrystalline HA crystals .about.40 nm in size.

  9. Climate change: Clinton affirms binding emissions reduction policy

    SciTech Connect (OSTI)

    Fairley, P.

    1996-12-04

    In Australia last month President Clinton called for an international agreement to negotiate {open_quotes}legally binding commitments to fight climate change.{close_quotes} His comments affirmed the line the Administration adopted in July and lent prominence to the effort to bring about a treaty by December 1997. Environmentalists welcomed Clinton`s comments, but industry response is divided. The Global Climate Coalition (Washington), of which CMA is a member, has tried to slow negotiations by questioning the scientific consensus on climate change and suggesting {open_quotes}serious damage to the American economy{close_quotes} could result from emissions reduction.

  10. Functionalized polymers for binding to solutes in aqueous solutions

    DOE Patents [OSTI]

    Smith, Barbara F.; Robison, Thomas W.

    2006-11-21

    A functionalized polymer for binding a dissolved molecule in an aqueous solution is presented. The polymer has a backbone polymer to which one or more functional groups are covalently linked. The backbone polymer can be such polymers as polyethylenimine, polyvinylamine, polyallylamine, and polypropylamine. These polymers are generally water-soluble, but can be insoluble when cross-linked. The functional group can be for example diol derivatives, polyol derivatives, thiol and dithiol derivatives, guest-host groups, affinity groups, beta-diphosphonic acids, and beta-diamides

  11. Characterization of Selective Binding of Alkali Cations with Carboxylate

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    AFDC Printable Version Share this resource Send a link to EERE: Alternative Fuels Data Center Home Page to someone by E-mail Share EERE: Alternative Fuels Data Center Home Page on Facebook Tweet about EERE: Alternative Fuels Data Center Home Page on Twitter Bookmark EERE: Alternative Fuels Data Center Homesum_a_epg0_fpd_mmcf_m.xls" ,"Available from WebQuantity ofkandz-cm11 OutreachProductswsicloudwsiclouddenDVA N C E D BGene Network ShapingDate:Characterization of Selective Binding of

  12. Relativistic Nuclear Energy Density Functionals: adjusting parameters to binding energies

    E-Print Network [OSTI]

    T. Niksic; D. Vretenar; P. Ring

    2008-09-08

    We study a particular class of relativistic nuclear energy density functionals in which only nucleon degrees of freedom are explicitly used in the construction of effective interaction terms. Short-distance (high-momentum) correlations, as well as intermediate and long-range dynamics, are encoded in the medium (nucleon density) dependence of the strength functionals of an effective interaction Lagrangian. Guided by the density dependence of microscopic nucleon self-energies in nuclear matter, a phenomenological ansatz for the density-dependent coupling functionals is accurately determined in self-consistent mean-field calculations of binding energies of a large set of axially deformed nuclei. The relationship between the nuclear matter volume, surface and symmetry energies, and the corresponding predictions for nuclear masses is analyzed in detail. The resulting best-fit parametrization of the nuclear energy density functional is further tested in calculations of properties of spherical and deformed medium-heavy and heavy nuclei, including binding energies, charge radii, deformation parameters, neutron skin thickness, and excitation energies of giant multipole resonances.

  13. Binding and structure of tetramers in the scaling limit

    E-Print Network [OSTI]

    Hadizadeh, M R; Tomio, L; Delfino, A; Frederico, T

    2011-01-01

    The momentum-space structure of the Faddeev-Yakubovsky (FY) components of weakly-bound tetramers is investigated at the unitary limit using a renormalized zero-range two-body interaction. The results, obtained by considering a given trimer level with binding energy $B_3$, provide further support to a universal scaling function relating the binding energies of two successive tetramer states. The correlated scaling between the tetramer energies comes from the sensitivity of the four-boson system to a short-range four-body scale. Each excited $N-$th tetramer energy $B_4^{(N)}$ moves as the short-range four-body scale changes, while the trimer properties are kept fixed, with the next excited tetramer $B_4^{(N+1)}$ emerging from the atom-trimer threshold for a universal ratio $B_4^{(N)}/B_3 = B_4^ {(N)}/B_4^{(N+1)} \\simeq 4.6$, which does not depend on $N$. We show that both channels of the FY decomposition [atom-trimer ($K-$type) and dimer-dimer ($H-$type)] present high momentum tails, which reflect the short-ran...

  14. Binding and structure of tetramers in the scaling limit

    E-Print Network [OSTI]

    M. R. Hadizadeh; M. T. Yamashita; L. Tomio; A. Delfino; T. Frederico

    2012-01-17

    The momentum-space structure of the Faddeev-Yakubovsky (FY)components of weakly-bound tetramers is investigated at the unitary limit using a renormalized zero-range two-body interaction. The results, obtained by considering a given trimer level with binding energy $B_3$, provide further support to a universal scaling function relating the binding energies of two successive tetramer states. The correlated scaling between the tetramer energies comes from the sensitivity of the four-boson system to a short-range four-body scale. Each excited $N-$th tetramer energy $B_4^{(N)}$ moves as the short-range four-body scale changes, while the trimer properties are kept fixed, with the next excited tetramer $B_4^{(N+1)}$ emerging from the atom-trimer threshold for a universal ratio $B_4^{(N)}/B_3 = B_4^ {(N)}/B_4^{(N+1)} \\simeq 4.6$, which does not depend on $N$. We show that both channels of the FY decomposition [atom-trimer ($K-$type) and dimer-dimer ($H-$type)] present high momentum tails, which reflect the short-range four-body scale. We also found that the $H-$channel is favored over $K-$channel at low momentum when the four-body momentum scale largely overcomes the three-body one.

  15. Binding of transcription factors adapts to resolve information-energy trade-off

    E-Print Network [OSTI]

    Kagan, Yonatan Savir Jacob

    2015-01-01

    We examine the binding of transcription factors to DNA in terms of an information transfer problem. The input of the noisy channel is the biophysical signal of a factor bound to a DNA site, and the output is a distribution of probable DNA sequences at this site. This task involves an inherent tradeoff between the information gain and the energetics of the binding interaction - high binding energies provide higher information gain but hinder the dynamics of the system as factors are bound too tightly. We show that adaptation of the binding interaction towards increasing information transfer under energy constraints implies that the information gain per specific binding energy at each base-pair is maximized. We analyze hundreds of prokaryote and eukaryote transcription factors from various organisms to evaluate the discrimination energies. We find that, in accordance with our theoretical argument, binding energies nearly maximize the information gain per energy. This work suggests the adaptation of information ...

  16. Evolutionary patterns of group B Sox binding and function in Drosophila

    E-Print Network [OSTI]

    Carl, Sarah Hamilton

    2015-04-07

    ChIP-seq reads and input reads from three biological replicates in D. pseudoobscura . . . . . . . . . . . . . . . . . . . . 89 4.1 Reproducibility of biological replicate DamID samples . . . . . . . 97 4.2 Translated reads for Sox fusion proteins... ) is to bind DNA and regulate the expression of target genes; however, the complexity of combinatorial binding patterns and the sheer quantity of binding events, even in the model organism Drosophila, which has a smaller and more compact genome than hu- mans...

  17. Sequestering Uranium from Seawater: Binding Strength and Modes of Uranyl Complexes with Glutarimidedioxime

    E-Print Network [OSTI]

    Tian, Guoxin

    2013-01-01

    binding strength and modes of uranyl complexes withand the coordination modes in the uranyl glutarimidedioximeof the bonding orbitals of uranyl (? u , ? g , ? u and ? g )

  18. Binding kinetics of membrane-anchored receptors and ligands: molecular dynamics simulations and theory

    E-Print Network [OSTI]

    Jinglei Hu; Guang-Kui Xu; Reinhard Lipowsky; Thomas R. Weikl

    2015-11-24

    The adhesion of biological membranes is mediated by the binding of membrane-anchored receptor and ligand proteins. Central questions are how the binding kinetics of these proteins is affected by the membranes and by the membrane anchoring of the proteins. In this article, we (i) present detailed data for the binding of membrane-anchored proteins from coarse-grained molecular dynamics simulations, and (ii) provide a theory that describes how the binding kinetics depends on the average separation and thermal roughness of the adhering membranes, and on the anchoring, lengths, and length variations of the proteins. An important element of our theory is the tilt of bound receptor-ligand complexes and transition-state complexes relative to the membrane normals. This tilt results from an interplay of the anchoring energy and rotational entropy of the complexes and facilitates the formation of receptor-ligand bonds at membrane separations smaller than the preferred separation for binding. In our simulations, we have considered both lipid-anchored and transmembrane receptor and ligand proteins. We find that the binding equilibrium constant and binding on-rate constant of lipid-anchored proteins are considerably smaller than the binding constant and on-rate constant of rigid transmembrane proteins with identical binding domains.

  19. Energy landscapes for protein folding, binding, and aggregation : simple funnels and beyond

    E-Print Network [OSTI]

    Cho, Samuel Sung-Il

    2007-01-01

    coordinates capture protein folding on smooth landscapes.in the Prediction of Protein Folding Kinetics. Proc. Natl.Landscapes for Protein Folding, Binding, and Aggregation:

  20. Binding Energies of the Alpha Particle and the A=3 Isobars from a Theoretical Geometric Model

    E-Print Network [OSTI]

    Gustavo R. Gonzalez-Martin

    2008-05-03

    We assume a triple geometric structure for the electromagnetic nuclear interaction. This nuclear electromagnetism is used to calculate the binding energies of the alpha particle and the A=3 isobar nuclides. The approximation for the resultant wave equation which lead to the deuteron binding energy from the modified Mathieu equation for the radial eigenvalue equation also establishes proton-electron-proton magnetic bonds in these nuclides and determines their binding energies. Completely theoretical calculations give 28.5 Mev., 7.64 Mev. and 8.42 Mev. for the binding energies of the alpha particle, the helium 3 isotope and tritium respectively. These values admit correction factors due to the approximations made.

  1. Sequestering Uranium from Seawater: Binding Strength and Modes of Uranyl Complexes with Glutarimidedioxime

    E-Print Network [OSTI]

    Tian, Guoxin

    2013-01-01

    data_request/cif. OECD, Uranium 2009: Resources, Productionthermodynamics of uranium, (H. Wanner and I. Forest,of California. Sequestering uranium from seawater: binding

  2. Mapping small molecule binding data to structural domains

    E-Print Network [OSTI]

    Kruger, Felix A.; Rostom, Raghd; Overington, John P.

    2012-12-07

    R_lig-bind 25 128 P40238 fn3 391 475 P48443 Nuc_recep-AF1 24 134 P48443 Hormone_recep 248 443 P48443 zf-C4 137 206 P54219 MFS_1 77 433 P54219 MFS_1 422 493 Q92813 T4_deiodinase 4 262 P08506 PBP5_C 285 376 P08506 Peptidase_S11 28 266 P10826 Hormone_recep 222 406... P10826 zf-C4 86 155 P10828 Hormone_recep 257 445 P10828 zf-C4 105 176 P11926 Orn_Arg_deC_N 44 282 P11926 Orn_DAP_Arg_deC 285 408 P19793 Nuc_recep-AF1 16 127 P19793 Hormone_recep 251 442 P19793 zf-C4 133 202 P27815 PDEase_I 432 676 P28702 Hormone...

  3. On the nuclear interaction. Potential, binding energy and fusion reaction

    E-Print Network [OSTI]

    I. Casinos

    2008-05-22

    The nuclear interaction is responsible for keeping neutrons and protons joined in an atomic nucleus. Phenomenological nuclear potentials, fitted to experimental data, allow one to know about the nuclear behaviour with more or less success where quantum mechanics is hard to be used. A nuclear potential is suggested and an expression for the potential energy of two nuclear entities, either nuclei or nucleons, is developed. In order to estimate parameters in this expression, some nucleon additions to nuclei are considered and a model is suggested as a guide of the addition process. Coulomb barrier and energy for the addition of a proton to each one of several nuclei are estimated by taking into account both the nuclear and electrostatic components of energy. Studies on the binding energies of several nuclei and on the fusion reaction of two nuclei are carried out.

  4. Quasielastic electron-deuteron scattering in the weak binding approximation

    SciTech Connect (OSTI)

    Ethier, Jacob J. [William and Mary College, JLAB; Doshi, Nidhi P. [Carnegie Mellon University; Malace, Simona P. [JLAB; Melnitchouk, Wally [JLAB

    2014-06-01

    We perform a global analysis of all available electron-deuteron quasielastic scattering data using Q^2-dependent smearing functions that describe inclusive inelastic e-d scattering within the weak binding approximation. We study the dependence of the cross sections on the deuteron wave function and the off-shell extrapolation of the elastic electron-nucleon cross section, which show particular sensitivity at x >> 1. The excellent overall agreement with data over a large range of Q^2 and x suggest a limited need for effects beyond the impulse approximation, with the exception of the very high-x or very low-Q^2 regions, where short-distance effects in the deuteron become more relevant.

  5. Development of Gamma-Emitting Receptor Binding Radiopharmace

    SciTech Connect (OSTI)

    Reba, Richard

    2003-02-20

    The long-term objective is to develop blood-brain barrier (BBB) permeable m2-selective (relative to m1, m3, and m4) receptor-binding radiotracers and utilize these radiotracers for quantifying receptor concentrations obtained from PET or SPECT images of human brain. In initial studies, we concluded that the lipophilicity and high affinity prevented (R,S)-I-QNB from reaching a flow-independent and receptor-dependent state in a reasonable time. Thus, it was clear that (R,S)-I-QNB should be modified. Therefore, during the last portion of this funded research, we proposed that more polar heterocycles should help accomplish that. Since reports of others concluded that radiobromination and radiofluorination of the unactivated phenyl ring is not feasible (Newkome et al,,1982), we, therefore, explored during this grant period a series of analogues of (R)-QNB in which one or both of the six-membered phenyl rings is replaced by a five-membered thienyl (Boulay et al., 1995), or furyl ring. The chemistry specific aims were to synthesize novel compounds designed to be m2-selective mAChR ligands capable of penetrating into the CNS, and develop methods for efficient radiolabeling of promising m2-selective muscarinic ligands. The pharmacology specific aims were to determine the affinity and subtype-selectivity of the novel compounds using competition binding studies with membranes from cells that express each of the five muscarinic receptor subtypes, to determine the ability of the promising non-radioactive compounds and radiolabeled novel compounds to cross the BBB, to determine the biodistribution, in-vivo pharmacokinetics, and in-vitm kinetics of promising m2-selective radioligands and to determine the distribution of receptors for the novel m2-selective radioligands using quantitative autoradiography of rat brain, and compare this distribution to the distribution of known m2-selective compounds.

  6. Single-Molecule Dynamics Reveals Cooperative Binding-Folding in Protein Recognition

    SciTech Connect (OSTI)

    Wang, Jin; Lu, Qiang N.; Lu, H PETER.

    2006-07-01

    The study of associations between two biomolecules is the key to understand molecular recognition and function. Molecular function is often thought to be determined by the underlying structures. Here, combining single molecule study of protein binding with an energy landscape inspired microscopic model, we found strong evidences that bio-molecular recognition is determined by flexibilities in addition to structures. Our model is based on coarse grained molecular dynamics performed on the residue level with the energy function biased towards the native binding structure (Go model). With our model, the underlying free energy landscape of the binding can be explored. Two distinct conformational states as free energy minimum, one with partially folding of CBD and significant binding of CBD to CDC42, and another with native folding of CBD and native binding of CBD to CDC42, are clearly seen. This shows the binding process proceeds with significant interface binding of CBD with CDC42 first without complete folding of CBD. Finally binding and folding are coupled with each other cooperatively to reach the native binding state. The single molecule experimental finding of the dynamic fluctuations between the loosely bound and closely bound conformational states can be identified with theoretically calculated free energy minimum and quantitatively explained in our model as a result of binding associated with large conformational changes. Theoretical predictions have identified certain key residues for binding which are consistent with mutational experiments. The combined study provides a test ground for fundamental mechanisms as well as insights into design and further explorations on biomolecular recognition with large conformational changes.

  7. Discriminating binding mechanisms of an intrinsically disordered protein via a multi-state coarse-grained model

    SciTech Connect (OSTI)

    Knott, Michael [Department of Chemistry, Cambridge University, Lensfield Road, Cambridge CB2 1EW (United Kingdom)] [Department of Chemistry, Cambridge University, Lensfield Road, Cambridge CB2 1EW (United Kingdom); Best, Robert B., E-mail: robertbe@helix.nih.gov [Department of Chemistry, Cambridge University, Lensfield Road, Cambridge CB2 1EW (United Kingdom); Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-0520 (United States)

    2014-05-07

    Many proteins undergo a conformational transition upon binding to their cognate binding partner, with intrinsically disordered proteins (IDPs) providing an extreme example in which a folding transition occurs. However, it is often not clear whether this occurs via an induced fit or conformational selection mechanism, or via some intermediate scenario. In the first case, transient encounters with the binding partner favour transitions to the bound structure before the two proteins dissociate, while in the second the bound structure must be selected from a subset of unbound structures which are in the correct state for binding, because transient encounters of the incorrect conformation with the binding partner are most likely to result in dissociation. A particularly interesting situation involves those intrinsically disordered proteins which can bind to different binding partners in different conformations. We have devised a multi-state coarse-grained simulation model which is able to capture the binding of IDPs in alternate conformations, and by applying it to the binding of nuclear coactivator binding domain (NCBD) to either ACTR or IRF-3 we are able to determine the binding mechanism. By all measures, the binding of NCBD to either binding partner appears to occur via an induced fit mechanism. Nonetheless, we also show how a scenario closer to conformational selection could arise by choosing an alternative non-binding structure for NCBD.

  8. USING DNASE DIGESTION DATA TO ACCURATELY IDENTIFY TRANSCRIPTION FACTOR BINDING SITES

    E-Print Network [OSTI]

    Hartemink, Alexander

    USING DNASE DIGESTION DATA TO ACCURATELY IDENTIFY TRANSCRIPTION FACTOR BINDING SITES KAIXUAN LUO1. But methods combining DNase digestion data with TF binding specificity information could potentially be used on the genomic digestion prod- ucts of deoxyribonuclease I (DNase I, which we will simply call DNase) might

  9. ContextSensitive Binding by the Laminar Circuits of V1 and V2

    E-Print Network [OSTI]

    Grossberg, Stephen

    ContextSensitive Binding by the Laminar Circuits of V1 and V2: Unified Model Perceptual Grouping is presented how laminar circuits visual cortical areas implement contextsensitive binding processes such perceptual grouping and attention. model proposes how specific laminar circuits allow responses visual

  10. Kinetics of Bile Salt Binding to Liposomes Revealed by Carboxyfluorescein Release and

    E-Print Network [OSTI]

    Hinow, Peter

    Kinetics of Bile Salt Binding to Liposomes Revealed by Carboxyfluorescein Release and Mathematical by the binding of different bile salts to the leaflets of the lipid bilayer. We find that the permeability of the liposomal bilayer depends on the difference in the concentrations of bile salt in the inner and outer

  11. Contributions to the Binding Free Energy of Ligands to Avidin and Streptavidin

    E-Print Network [OSTI]

    Lazaridis, Themis

    of New York, New York, New York ABSTRACT The free energy of binding of a ligand to a macromoleculeContributions to the Binding Free Energy of Ligands to Avidin and Streptavidin Themis Lazaridis is here formally decom- posed into the (effective) energy of interaction, reorganization energy

  12. Using Multiconformation Continuum Electrostatics to Compare Chloride Binding Motifs in -Amylase,

    E-Print Network [OSTI]

    Gunner, Marilyn

    Using Multiconformation Continuum Electrostatics to Compare Chloride Binding Motifs in -Amylase electrostatics (MCCE), we show that the changes of chloride binding to -amylase, human serum albumin (HSA) and Omp32 with pH, and of -amylase with mutation agree well with experimental data. The three proteins

  13. Retention of Conformational Entropy upon Calmodulin Binding to Target Peptides is Driven by Transient Salt Bridges

    SciTech Connect (OSTI)

    Smith, Dayle MA; Straatsma, TP; Squier, Thomas C.

    2012-10-03

    Calmodulin (CaM) is a highly flexible calcium-binding protein that mediates signal transduction through an ability to differentially bind to highly variable binding sequences in target proteins. To identify how binding affects CaM motions, and its relationship to conformational entropy and target peptide sequence, we have employed fully atomistic, explicit solvent molecular dynamics simulations of unbound CaM and CaM bound to five different target peptides. The calculated CaM conformational binding entropies correlate with experimentally derived conformational entropies with a correlation coefficient R2 of 0.95. Selected side-chain interactions with target peptides restrain interhelical loop motions, acting to tune the conformational entropy of the bound complex via widely distributed CaM motions. In the complex with the most conformational entropy retention (CaM in complex with the neuronal nitric oxide synthase binding sequence), Lys-148 at the C-terminus of CaM forms transient salt bridges alternating between Glu side chains in the N-domain, the central linker, and the binding target. Additional analyses of CaM structures, fluctuations, and CaM-target interactions illuminate the interplay between electrostatic, side chain, and backbone properties in the ability of CaM to recognize and discriminate against targets by tuning its conformational entropy, and suggest a need to consider conformational dynamics in optimizing binding affinities.

  14. Distinct p53 genomic binding patterns in normal and cancer-derived human cells

    SciTech Connect (OSTI)

    Botcheva K.; McCorkle S. R.; McCombie W. R.; Dunn J. J.; Anderson C. W.

    2011-12-15

    We report here genome-wide analysis of the tumor suppressor p53 binding sites in normal human cells. 743 high-confidence ChIP-seq peaks representing putative genomic binding sites were identified in normal IMR90 fibroblasts using a reference chromatin sample. More than 40% were located within 2 kb of a transcription start site (TSS), a distribution similar to that documented for individually studied, functional p53 binding sites and, to date, not observed by previous p53 genome-wide studies. Nearly half of the high-confidence binding sites in the IMR90 cells reside in CpG islands, in marked contrast to sites reported in cancer-derived cells. The distinct genomic features of the IMR90 binding sites do not reflect a distinct preference for specific sequences, since the de novo developed p53 motif based on our study is similar to those reported by genome-wide studies of cancer cells. More likely, the different chromatin landscape in normal, compared with cancer-derived cells, influences p53 binding via modulating availability of the sites. We compared the IMR90 ChIPseq peaks to the recently published IMR90 methylome1 and demonstrated that they are enriched at hypomethylated DNA. Our study represents the first genome-wide, de novo mapping of p53 binding sites in normal human cells and reveals that p53 binding sites reside in distinct genomic landscapes in normal and cancer-derived human cells.

  15. Identification of Substrate Binding Sites in Enzymes by Computational Solvent Mapping

    E-Print Network [OSTI]

    Vajda, Sandor

    . Dennis, Biotechnology Research Institute, National Research Council of Canada, Montreal, Canada; L. Brown * 1 Program in Bioinformatics Boston University, Boston, MA 02215, USA 2 Department of Biomedical with the most favorable binding free energy. The method then finds the con- sensus site that binds the highest

  16. A PARLOG Implementation of Government-Binding Theory Robert J. Kuhns

    E-Print Network [OSTI]

    on the principles and constraints of Government- Binding Theory. The parser outputs a set of licensing relations~odules of tile theory. BACKGROUND Parse,'s based oil Government-Binding (GB) Theory have been tile subject\\er, they all approach parsing as a sequential process, and allhough there have been a number o[' efforts oil

  17. STAR/MPI: Binding a Parallel Library to Interactive Symbolic Algebra Systems

    E-Print Network [OSTI]

    Cooperman, Gene

    STAR/MPI: Binding a Parallel Library to Interactive Symbolic Algebra Systems Gene Cooperman 1 gene of symbolic algebra systems have felt the need for greater CPU power. Yet few of them have ventured/MPI includes a simple SPMD architecture on top of this MPI binding. An important class of sequential algo

  18. Dynamics of intracellular Ca$^{2+}$ oscillations in the presence of multisite Ca$^{2+}$-binding proteins

    E-Print Network [OSTI]

    Roberto Chignola; Alessio Del Fabbro; Edoardo Milotti

    2009-09-10

    We study the dynamics of intracellular calcium oscillations in the presence of proteins that bind calcium on multiple sites and that are generally believed to act as passive calcium buffers in cells. We find that multisite calcium-binding proteins set a sharp threshold for calcium oscillations. Even with high concentrations of calcium-binding proteins, internal noise, which shows up spontaneously in cells in the process of calcium wave formation, can lead to self-oscillations. This produces oscillatory behaviors strikingly similar to those observed in real cells. In addition, for given intracellular concentrations of both calcium and calcium-binding proteins the regularity of these oscillations changes and reaches a maximum as a function noise variance, and the overall system dynamics displays stochastic coherence. We conclude that calcium-binding proteins may have an important and active role in cellular communication.

  19. Expression, purification, crystallization and structure of human adipocyte lipid-binding protein (aP2)

    SciTech Connect (OSTI)

    Marr, Eric; Tardie, Mark; Carty, Maynard; Brown Phillips, Tracy; Wang, Ing-Kae; Soeller, Walt; Qiu, Xiayang Karam, George

    2006-11-01

    The crystal structure of human adipocyte lipid-binding protein (aP2) with a bound palmitate is reported at 1.5 resolution. Human adipocyte lipid-binding protein (aP2) belongs to a family of intracellular lipid-binding proteins involved in the transport and storage of lipids. Here, the crystal structure of human aP2 with a bound palmitate is described at 1.5 resolution. Unlike the known crystal structure of murine aP2 in complex with palmitate, this structure shows that the fatty acid is in a folded conformation and that the loop containing Phe57 acts as a lid to regulate ligand binding by excluding solvent exposure to the central binding cavity.

  20. Conformational Variability of Organophosphorus Hydrolase upon Soman and Paraoxon Binding

    SciTech Connect (OSTI)

    Gomes, Diego Eb; Lins, Roberto D.; Pascutti, Pedro G.; Lei, Chenghong; Soares, Thereza A.

    2011-12-31

    The bacterial enzyme organophosphorus hydrolase (OPH) exhibits both catalytic and substrate promiscuity. It hydrolyzes bonds in a variety of phosphotriester (P-O), phosphonothioate (P-S), phosphofluoridate (P-F) and phosphonocyanate (F-CN) compounds. However, its catalytic efficiency varies markedly for different substrates, limiting the broad-range application of OPH as catalyst in the bioremediation of pesticides and chemical war agents. In the present study, pK{sub a} calculations and multiple explicit-solvent molecular dynamics (MD) simulations were performed to characterize and contrast the structural dynamics of OPH bound to two substrates hydrolyzed with very distinct catalytic efficiencies: the nerve agent soman (O-pinacolyl-methyl-phosphonofluoridate) and the pesticide paraoxon (diethyl p-nitrophenyl phosphate). pK{sub a} calculations for the substrate-bound and unbound enzyme showed a significant pK{sub a} shift from standard values ({Delta}pK{sub a} = {+-} 3 units) for residues 254His and 275Arg. MD simulations of the doubly protonated 254His revealed a dynamic hydrogen bond network connecting the catalytic residue 301Asp via 254His to 232Asp, 233Asp, 275Arg and 235Asp, and is consistent with a previously postulated proton relay mechanism to ferry protons away from the active site with substrates that do not require activation of the leaving group. Hydrogen bonds between 301Asp and 254His were persistent in the OPH-paraoxon complex but not in the OPH-soman one, suggesting a potential role for such interaction in the more efficient hydrolysis of paraoxon over soman by OPH. These results are in line with previous mutational studies of residue 254His, which led to an increase of the catalytic efficiency of OPH over soman yet decreased its efficiency for paraoxon. In addition, comparative analysis of the molecular trajectories for OPH bound to soman and paraoxon suggests that binding of the latter facilitates the conformational transition of OPH from the open to the closed substate promoting a tighter binding of paraoxon.

  1. Structural basis of substrate discrimination and integrin binding by autotaxin

    SciTech Connect (OSTI)

    Hausmann, Jens; Kamtekar, Satwik; Christodoulou, Evangelos; Day, Jacqueline E.; Wu, Tao; Fulkerson, Zachary; Albers, Harald M.H.G.; van Meeteren, Laurens A.; Houben, Anna J.S.; van Zeijl, Leonie; Jansen, Silvia; Andries, Maria; Hall, Troii; Pegg, Lyle E.; Benson, Timothy E.; Kasiem, Mobien; Harlos, Karl; Vander Kooi, Craig W.; Smyth, Susan S.; Ovaa, Huib; Bollen, Mathieu; Morris, Andrew J.; Moolenaar, Wouter H.; Perrakis, Anastassis (Pfizer); (Leuven); (Oxford); (NCI-Netherlands); (Kentucky)

    2013-09-25

    Autotaxin (ATX, also known as ectonucleotide pyrophosphatase/phosphodiesterase-2, ENPP2) is a secreted lysophospholipase D that generates the lipid mediator lysophosphatidic acid (LPA), a mitogen and chemoattractant for many cell types. ATX-LPA signaling is involved in various pathologies including tumor progression and inflammation. However, the molecular basis of substrate recognition and catalysis by ATX and the mechanism by which it interacts with target cells are unclear. Here, we present the crystal structure of ATX, alone and in complex with a small-molecule inhibitor. We have identified a hydrophobic lipid-binding pocket and mapped key residues for catalysis and selection between nucleotide and phospholipid substrates. We have shown that ATX interacts with cell-surface integrins through its N-terminal somatomedin B-like domains, using an atypical mechanism. Our results define determinants of substrate discrimination by the ENPP family, suggest how ATX promotes localized LPA signaling and suggest new approaches for targeting ATX with small-molecule therapeutic agents.

  2. Donor binding energy and thermally activated persistent photoconductivity in high mobility ,,001... AlAs quantum wells

    E-Print Network [OSTI]

    Grayson, Matthew

    material parameters such as the donor binding energy and doping efficiency have been obscured by substrateDonor binding energy and thermally activated persistent photoconductivity in high mobility ,,001. Graysonb Department of Electrical Engineering and Computer Science, Northwestern University, Evanston

  3. Role of RNA Binding Proteins and Post-Transcriptional Regulation in Response to Environmental Changes in Arabidopsis thaliana

    E-Print Network [OSTI]

    Juntawong, Piyada

    2010-01-01

    Burd, C. G. 1993. hnRNP proteins and the biogenesis of mRNA.2002. Messenger-RNA-binding proteins and the messages theycruzi poly-zinc finger protein: a novel DNA/RNA-binding

  4. Characterization of anti-HIV-1 neutralizing and binding antibodies in chronic HIV-1 subtype C infection

    E-Print Network [OSTI]

    Archary, Derseree

    Neutralizing (nAbs) and high affinity binding antibodies may be critical for an efficacious HIV-1 vaccine. We characterized virus-specific nAbs and binding antibody responses over 21 months in eight HIV-1 subtype C chronically ...

  5. Sulfolobus shibatae CCA-adding Enzyme Forms a Tetramer upon Binding Two tRNA Molecules: A

    E-Print Network [OSTI]

    Li, Fang

    Sulfolobus shibatae CCA-adding Enzyme Forms a Tetramer upon Binding Two tRNA Molecules to form a tetramer is induced by the binding of two tRNA molecules. The formation of a tetramer with only

  6. Binding information in short-term memory: evidence from healthy individuals, Alzheimer's Disease and other clinical populations

    E-Print Network [OSTI]

    Rodrguez, Mario Alfredo Parra

    Memory binding is a cognitive process that enables complex objects to be stored or retrieved coherently during perception, learning, or action. Binding functions are aimed at reducing the misattribution of the features ...

  7. NMR studies of DNA oligomers and their interactions with minor groove binding ligands

    SciTech Connect (OSTI)

    Fagan, P A [Univ. of California, Berkeley, CA (United States). Dept. of Chemistry

    1996-05-01

    The cationic peptide ligands distamycin and netropsin bind noncovalently to the minor groove of DNA. The binding site, orientation, stoichiometry, and qualitative affinity of distamycin binding to several short DNA oligomers were investigated by NMR spectroscopy. The oligomers studied contain A,T-rich or I,C-rich binding sites, where I = 2-desaminodeoxyguanosine. I{center_dot}C base pairs are functional analogs of A{center_dot}T base pairs in the minor groove. The different behaviors exhibited by distamycin and netropsin binding to various DNA sequences suggested that these ligands are sensitive probes of DNA structure. For sites of five or more base pairs, distamycin can form 1:1 or 2:1 ligand:DNA complexes. Cooperativity in distamycin binding is low in sites such as AAAAA which has narrow minor grooves, and is higher in sites with wider minor grooves such as ATATAT. The distamycin binding and base pair opening lifetimes of I,C-containing DNA oligomers suggest that the I,C minor groove is structurally different from the A,T minor groove. Molecules which direct chemistry to a specific DNA sequence could be used as antiviral compounds, diagnostic probes, or molecular biology tools. The author studied two ligands in which reactive groups were tethered to a distamycin to increase the sequence specificity of the reactive agent.

  8. Assessing Energetic Contributions to Binding from a Disordered Region in a Protein-Protein Interaction

    SciTech Connect (OSTI)

    S Cho; C Swaminathan; D Bonsor; M Kerzic; R Guan; J Yang; C Kieke; P Anderson; D Kranz; et al.

    2011-12-31

    Many functional proteins are at least partially disordered prior to binding. Although the structural transitions upon binding of disordered protein regions can influence the affinity and specificity of protein complexes, their precise energetic contributions to binding are unknown. Here, we use a model protein-protein interaction system in which a locally disordered region has been modified by directed evolution to quantitatively assess the thermodynamic and structural contributions to binding of disorder-to-order transitions. Through X-ray structure determination of the protein binding partners before and after complex formation and isothermal titration calorimetry of the interactions, we observe a correlation between protein ordering and binding affinity for complexes along this affinity maturation pathway. Additionally, we show that discrepancies between observed and calculated heat capacities based on buried surface area changes in the protein complexes can be explained largely by heat capacity changes that would result solely from folding the locally disordered region. Previously developed algorithms for predicting binding energies of protein-protein interactions, however, are unable to correctly model the energetic contributions of the structural transitions in our model system. While this highlights the shortcomings of current computational methods in modeling conformational flexibility, it suggests that the experimental methods used here could provide training sets of molecular interactions for improving these algorithms and further rationalizing molecular recognition in protein-protein interactions.

  9. Cell, Vol. 94, 181191, July 24, 1998, Copyright 1998 by Cell Press Crystal Structure of the Signal Sequence Binding

    E-Print Network [OSTI]

    Walter, Peter

    Cell, Vol. 94, 181191, July 24, 1998, Copyright 1998 by Cell Press Crystal Structure). During targeting, the Ffh- The crystal structure of the signal sequence binding 4.5S RNA complex binds domain is a four-helix to the structural plasticity necessary for SRP to bind bundle that is closely

  10. Free Energy Component Analysis for Drug Design: A Case Study of HIV-1 Protease-Inhibitor Binding

    E-Print Network [OSTI]

    Jayaram, Bhyravabotla

    Free Energy Component Analysis for Drug Design: A Case Study of HIV-1 Protease-Inhibitor Binding of the free energies of binding of protein-ligand complexes is presented. The method formulated involves, and the trajectories were analyzed via a thermodynamic cycle to calculate the binding free energies. The computed free

  11. 1 Plasmodium falciparum SSB Tetramer Binds 2 Single-Stranded DNA Only in a Fully Wrapped Mode

    E-Print Network [OSTI]

    Lohman, Timothy M.

    1 Plasmodium falciparum SSB Tetramer Binds 2 Single-Stranded DNA Only in a Fully Wrapped Mode 3 with numerous DNA repair and replication proteins. Ec- 24 SSB tetramers can bind ssDNA in multiple DNA binding in fully wrapped complexes with site sizes of 30 5265 nt/tetramer. Pf-SSB does not transition to the more

  12. A Ternary Metal Binding Site in the C2 Domain of Phosphoinositide-Specific Phospholipase C-1,

    E-Print Network [OSTI]

    Williams, Roger L.

    A Ternary Metal Binding Site in the C2 Domain of Phosphoinositide-Specific Phospholipase C-1, Lars. Binding of these metal ions is observed in the active site of the catalytic TIM barrel and in the calcium adjacent binding sites in the C2 domain were observed for calcium and the other metal/enzyme complexes

  13. Method for detecting binding events using micro-X-ray fluorescence spectrometry

    DOE Patents [OSTI]

    Warner, Benjamin P. (Los Alamos, NM); Havrilla, George J. (Los Alamos, NM); Mann, Grace (Hong Kong, HK)

    2010-12-28

    Method for detecting binding events using micro-X-ray fluorescence spectrometry. Receptors are exposed to at least one potential binder and arrayed on a substrate support. Each member of the array is exposed to X-ray radiation. The magnitude of a detectable X-ray fluorescence signal for at least one element can be used to determine whether a binding event between a binder and a receptor has occurred, and can provide information related to the extent of binding between the binder and receptor.

  14. Studies on immunoglobulins and complement binding to the surface of Schistosoma mansoni

    E-Print Network [OSTI]

    Rasmussen, Kathleen Ruth

    1983-01-01

    of these adsorbed immunoglobulins is presumed to be by the Fc portion of the immunoglobul1n to Fc receptors on the worm because such adsorbed immunoglobulins are able to bind the antigens to which they were elicited. Torpier et al. (26) demonstrated Fc receptors.... , Texas A&M University Chairman of Advisory Committee: Walter Michael Kemp (Ph. D. ) An indirect assay was used to detect binding of Fc associated specific anti-schistosome antibody (homospec1fic antibody) to adult male schistosomes. Binding...

  15. Stoichiometry of Complexes between Mannose-binding Protein and Its Associated Serine Proteases

    E-Print Network [OSTI]

    of the innate immune response. It binds to sugars on the surfaces of pathogenic microorganisms and activates on the surfaces of microorganisms and activating two MBP-associated serine proteases (MASP-1 and MASP-2). Rat

  16. Molecular Defects in Variant Forms of Mannose-Binding Protein Associated with Immunodeficiency1

    E-Print Network [OSTI]

    of the first lines of defense against invasion by pathogenic microorganisms (1, 2). MBPs bind to sugar to generate fragments that have C3- convertase activity (38). Microorganisms are neutralized either

  17. Engineering Encodable Lanthanide-Binding Tags (LBTs) into Loop Regions of Proteins

    E-Print Network [OSTI]

    Barthelmes, Katja

    Lanthanide-binding tags (LBTs) are valuable tools for investigation of protein structure, function, and dynamics by NMR spectroscopy, X-ray crystallography, and luminescence studies. We have inserted LBTs into three different ...

  18. Rational Design of New Binding Specificity by Simultaneous Mutagenesis of Calmodulin and a Target Peptide

    E-Print Network [OSTI]

    Green, David F.

    Calcium-saturated calmodulin (CaM) binds and influences the activity of a varied collection of target proteins in most cells. This promiscuity underlies the role of CaM as a shared participant in calcium-dependent signal ...

  19. Structural and functional consequences of platinum anticancer drug binding to free and nucleosomal DNA

    E-Print Network [OSTI]

    Todd, Ryan Christopher, 1981-

    2010-01-01

    Cisplatin, carboplatin, and oxaliplatin are three FDA-approved members of the platinum anticancer drug family. These compounds induce apoptosis in tumor cells by binding to nuclear DNA, forming a variety of adducts, and ...

  20. How Plasmodium falciparum malaria parasites bind to human brain endothelial cells

    E-Print Network [OSTI]

    Claessens, Antoine

    2011-01-01

    Cerebral malaria is characterised by an accumulation of infected erythrocytes in the microvasculature of the brain. Plasmodium falciparum infected erythrocytes have been shown to bind to a Human Brain Endothelial Cell line (HBEC-5i) in vitro...

  1. Control of HslUV protease function by nucleotide binding and hydrolysis

    E-Print Network [OSTI]

    Yakamavich, Joseph Andrew

    2008-01-01

    Many proteins act as molecular machines, using the power of nucleotide binding and hydrolysis to drive conformational changes in themselves and their target substrates. Like other AAA+ proteases, HslUV recognizes, unfolds, ...

  2. Analysis of variation at transcription factor binding sites in Drosophila and humans

    E-Print Network [OSTI]

    Spivakov, Mikhail

    Background: Advances in sequencing technology have boosted population genomics and made it possible to map the positions of transcription factor binding sites (TFBSs) with high precision. Here we investigate TFBS variability ...

  3. 2D IR spectroscopy and computational modeling : application to protein folding and binding

    E-Print Network [OSTI]

    Ganim, Ziad

    2010-01-01

    In this thesis, dynamics experiments are developed that can be used to study protein conformational changes such as folding and binding. Every functional motion of a protein is inextricably linked to conformational dynamics. ...

  4. Negatively Cooperative Binding of High-Density Lipoprotein to the HDL Receptor SR-BI

    E-Print Network [OSTI]

    Xu, Shangzhe

    Scavenger receptor class B, type I (SR-BI), is a high-density lipoprotein (HDL) receptor, which also binds low-density lipoprotein (LDL), and mediates the cellular selective uptake of cholesteryl esters from lipoproteins. ...

  5. Identification and analysis of hepatitis C virus NS3 helicase inhibitors using nucleic acid binding assays

    E-Print Network [OSTI]

    Mukherjee, Sourav; Hanson, Alica M.; Shadrick, William R.; Ndjomou, Jean; Sweeney, Noreena L.; Hernadez, John J.; Bartczak, Diana; Li, Kelin; Frankowski, Kevin J.; Heck, Julie A.; Arnold, Leggy A.; Schoenen, Frank; Frick, David N,

    2012-06-27

    Typical assays used to discover and analyze small molecules that inhibit the hepatitis C virus (HCV) NS3 helicase yield few hits and are often confounded by compound interference. Oligonucleotide binding assays are examined here as an alternative...

  6. V-058: Microsoft Internet Explorer CDwnBindInfo Object Reuse...

    Broader source: Energy.gov (indexed) [DOE]

    Microsoft Internet Explorer CDwnBindInfo Object Reuse Flaw Lets Remote Users Execute Arbitrary Code PLATFORM: Version(s): 6, 7, 8 ABSTRACT: A vulnerability was reported in...

  7. LETTER TO THE EDITOR Binding of manganese(II) to a tertiary stabilized

    E-Print Network [OSTI]

    Westhof, Eric

    as studied by electron paramagnetic resonance spectroscopy NATALIA KISSELEVA,1 ANASTASIA KHVOROVA,2 ERICII ions to a tertiary stabilized hammer- head ribozyme (tsHHRz) and to compare it with the binding

  8. Context influences on TALEDNA binding revealed by quantitative profiling

    E-Print Network [OSTI]

    Rogers, Julia M.

    Transcription activator-like effector (TALE) proteins recognize DNA using a seemingly simple DNA-binding code, which makes them attractive for use in genome engineering technologies that require precise targeting. Although ...

  9. Water growth on metals and oxides: binding, dissociation and role of hydroxyl groups

    E-Print Network [OSTI]

    Salmeron, M.

    2008-01-01

    Note: In this paper the water structures formed are due toand correspond to a second water layer, not the first (seeWater growth on metals and oxides: binding, dissociation and

  10. How the Nature of Information Affects Binding in Visual Working Memory

    E-Print Network [OSTI]

    Walt, Nicola

    2007-01-01

    The question of whether binding information affects the capacity of visual working memory has not been established to date. Different trends in thought have hypothesized different effects for the way information is stored ...

  11. Engineering and targeting glycan receptor binding of influenza A virus hemagglutinin

    E-Print Network [OSTI]

    Jayaraman, Akila

    2011-01-01

    The critical first step in the host infection by influenza A virus is the binding of the viral surface glycoprotein hemagglutinin (HA) to the sialylated glycan receptors terminated by N-acetyineuraminic acid (Neu5Ac) ...

  12. Effects of dietary fiber and carcinogen on fatty acid binding protein expression in exfoliated colonocytes

    E-Print Network [OSTI]

    Clark, Amy Eunice

    1997-01-01

    EFFECTS OF DIETARY FIBER AND CARCINOGEN ON FATTY ACID BINDING PROTEIN EXPRESSION IN EXFOLIATED COLONOCYTES A Thesis by AMY EUNICE CLARK Submitted to the Office of Gmduate Studies of Texas A&M University in partial fulfillment... of the requireinents for the degree of MASTER OF SCIENCE August 1997 Major Subject: Nutriuon EFFECTS OF DIETARY FIBER AND CARCINOGEN ON FATTY ACID BINDING PROTEIN EXPRESSION IN EXFOLlATED COLONOCYTES by AMY EUNICE CLARK Submitted to Texas ARM University...

  13. Statistical fluctuations of ground-state energies and binding energies in nuclei

    E-Print Network [OSTI]

    A. Molinari; H. A. Weidenmueller

    2004-03-11

    The statistical fluctuations of the ground-state energy and of the binding energy of nuclei are investigated using both perturbation theory and supersymmetry. The fluctuations are induced by the experimentally observed stochastic behavior of levels in the vicinity of neutron threshold. The results are compared with a recent analysis of binding-energy fluctuations by Bohigas and Leboeuf, and with theoretical work by Feshbach et al.

  14. Elevated epidermal growth factor receptor binding in plutonium-induced lung tumors from dogs

    SciTech Connect (OSTI)

    Leung, F.C.; Bohn, L.R.; Dagle, G.E. )

    1991-04-01

    The objective of this study is to examine and characterize epidermal growth factor receptor (EGF-R) binding in inhaled plutonium-induced canine lung-tumor tissue and to compare it with that in normal canine lung tissue. Crude membrane preparations from normal and lung-tumor tissue from beagle dogs were examined in a radioreceptor assay, using {sup 125}I-labeled epidermal growth factor (EGF) as a ligand. Specific EGF receptor binding was determined in the presence of excess unlabeled EGF. We have examined EGF receptor binding in eight lung-tumor samples obtained from six dogs. Epidermal growth factor receptor binding was significantly greater in lung-tumor samples (31.38%) compared with that in normal lung tissue (3.76%). Scatchard plot analysis from the displacement assay revealed that there was no statistical difference in the binding affinity but significantly higher concentration of EGF-R sites in the lung-tumor tissue (619 fmol/mg) than in normal lung tissue (53 fmol/mg). The increase in EGF-R number in plutonium-induced dog lung tumors does not seem to correlate with increase in the initial lung burden exposure to plutonium. Our results demonstrate that there is a significant increase in EGF-R binding in inhaled plutonium-induced dog lung tumors.

  15. In silico identification of anthropogenic chemicals as ligands of zebrafish sex hormone binding globulin

    SciTech Connect (OSTI)

    Thorsteinson, Nels; Ban, Fuqiang; Santos-Filho, Osvaldo; Tabaei, Seyed M.H. [Prostate Centre at the Vancouver General Hospital, University of British Columbia, 2660 Oak Street, Vancouver, BC, V6H 3Z6 (Canada); Miguel-Queralt, Solange; Underhill, Caroline [Department of Obstetrics and Gynecology, University of British Columbia, Child and Family Research Institute, 950 West 28th Avenue, Vancouver, BC, V5Z 4H4 (Canada); Cherkasov, Artem [Prostate Centre at the Vancouver General Hospital, University of British Columbia, 2660 Oak Street, Vancouver, BC, V6H 3Z6 (Canada)], E-mail: artc@interchange.ubc.ca; Hammond, Geoffrey L. [Department of Obstetrics and Gynecology, University of British Columbia, Child and Family Research Institute, 950 West 28th Avenue, Vancouver, BC, V5Z 4H4 (Canada)

    2009-01-01

    Anthropogenic compounds with the capacity to interact with the steroid-binding site of sex hormone binding globulin (SHBG) pose health risks to humans and other vertebrates including fish. Building on studies of human SHBG, we have applied in silico drug discovery methods to identify potential binders for SHBG in zebrafish (Danio rerio) as a model aquatic organism. Computational methods, including; homology modeling, molecular dynamics simulations, virtual screening, and 3D QSAR analysis, successfully identified 6 non-steroidal substances from the ZINC chemical database that bind to zebrafish SHBG (zfSHBG) with low-micromolar to nanomolar affinities, as determined by a competitive ligand-binding assay. We also screened 80,000 commercial substances listed by the European Chemicals Bureau and Environment Canada, and 6 non-steroidal hits from this in silico screen were tested experimentally for zfSHBG binding. All 6 of these compounds displaced the [{sup 3}H]5{alpha}-dihydrotestosterone used as labeled ligand in the zfSHBG screening assay when tested at a 33 {mu}M concentration, and 3 of them (hexestrol, 4-tert-octylcatechol, and dihydrobenzo(a)pyren-7(8H)-one) bind to zfSHBG in the micromolar range. The study demonstrates the feasibility of large-scale in silico screening of anthropogenic compounds that may disrupt or highjack functionally important protein:ligand interactions. Such studies could increase the awareness of hazards posed by existing commercial chemicals at relatively low cost.

  16. Functional characterization of acyl-CoA binding protein (ACBP) and oxysterol binding protein-related proteins (ORPS) from Cryptosporidium parvum

    E-Print Network [OSTI]

    Zeng, Bin

    2009-05-15

    From opportunistic protist Cryptosporidium parvum we identified and functionally assayed a fatty acyl-CoA-binding protein (ACBP) gene. The CpACBP1 gene encodes a protein of 268 aa that is three times larger than typical ~10 KD ACBPs of humans...

  17. Substrate binding by a bacterial ABC transporter involved in polysaccharide export

    SciTech Connect (OSTI)

    Cuthbertson, Leslie; Kimber, Matthew S.; Whitfield, Chris (Guelph)

    2008-04-02

    ATP-binding-cassette (ABC) transporters are responsible for the export of a wide variety of cell-surface glycoconjugates in both Gram-positive and Gram-negative bacteria. These include the O-antigenic polysaccharide (O-PS) portion of lipopolysaccharide, a crucial virulence determinant in Gram-negative pathogens. O-PSs are synthesized by one of two fundamentally different pathways. Escherichia coli O serotypes O8 and O9a provide the prototype systems for studying O-PS export via ABC transporters. The transporter is composed of the transmembrane component Wzm and the nucleotide-binding component Wzt. Although the N-terminal domain of Wzt is a conventional ABC protein, the C-terminal domain of Wzt (C-Wzt) is a unique structural element that determines the specificity of the transporter for either the O8 or O9a O-PS. We show here that the two domains of Wzt can function when expressed as separate polypeptides; both are essential for export. In vitro, C-Wzt binds its cognate O-PS by recognizing a residue located at the nonreducing end of the polymer. The crystal structure of C-WztO9a is reported here and reveals a {beta} sandwich with an immunoglobulin-like topology that contains the O-PS-binding pocket. Substrate interactions with nucleotide-binding domains have been demonstrated in an ABC exporter previously. However, to our knowledge substrate binding by a discrete, cytoplasmic accessory domain in an extended nucleotide-binding domain polypeptide has not previously been demonstrated. Elucidation of the substrate-recognition system involved in O-PS export provides insight into the mechanism that coordinates polymer biosynthesis, termination, and export.

  18. Binding of undamaged double stranded DNA to vaccinia virus uracil-DNA glycosylase

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Schormann, Norbert; Banerjee, Surajit; Ricciardi, Robert; Chattopadhyay, Debasish

    2015-06-02

    Background: Uracil-DNA glycosylases are evolutionarily conserved DNA repair enzymes. However, vaccinia virus uracil-DNA glycosylase (known as D4), also serves as an intrinsic and essential component of the processive DNA polymerase complex during DNA replication. In this complex D4 binds to a unique poxvirus specific protein A20 which tethers it to the DNA polymerase. At the replication fork the DNA scanning and repair function of D4 is coupled with DNA replication. So far, DNA-binding to D4 has not been structurally characterized. Results: This manuscript describes the first structure of a DNA-complex of a uracil-DNA glycosylase from the poxvirus family. This alsomorerepresents the first structure of a uracil DNA glycosylase in complex with an undamaged DNA. In the asymmetric unit two D4 subunits bind simultaneously to complementary strands of the DNA double helix. Each D4 subunit interacts mainly with the central region of one strand. DNA binds to the opposite side of the A20-binding surface on D4. In comparison of the present structure with the structure of uracil-containing DNA-bound human uracil-DNA glycosylase suggests that for DNA binding and uracil removal D4 employs a unique set of residues and motifs that are highly conserved within the poxvirus family but different in other organisms. Conclusion: The first structure of D4 bound to a truly non-specific undamaged double-stranded DNA suggests that initial binding of DNA may involve multiple non-specific interactions between the protein and the phosphate backbone.less

  19. E. coli SSB tetramer binds the rst and second molecules of (dT)35 with heat capacities of opposite sign

    E-Print Network [OSTI]

    Lohman, Timothy M.

    E. coli SSB tetramer binds the rst and second molecules of (dT)35 with heat capacities of opposite of the binding heat capacity ( CP). Here we examine SSB binding to shorter oligodeoxynucleotides ((dX)35) to probe whether this effect requires binding of one or two (dX)35 molecules per SSB tetramer. We nd

  20. Beyond the detergent effect: a binding site for sodium dodecyl sulfate (SDS) in mammalian apoferritin

    SciTech Connect (OSTI)

    Liu, Renyu Bu, Weiming; Xi, Jin; Mortazavi, Shirin R.; Cheung-Lau, Jasmina C.; Dmochowski, Ivan J.; Loll, Patrick J.

    2012-05-01

    Using X-ray crystallography and isothermal titration calorimetry, we show that sodium dodecyl sulfate (SDS) binds specifically to a pre-formed internal cavity in horse-spleen apoferritin. Although sodium dodecyl sulfate (SDS) is widely used as an anionic detergent, it can also exert specific pharmacological effects that are independent of the surfactant properties of the molecule. However, structural details of how proteins recognize SDS are scarce. Here, it is demonstrated that SDS binds specifically to a naturally occurring four-helix bundle protein: horse apoferritin. The X-ray crystal structure of the apoferritinSDS complex was determined at a resolution of 1.9 and revealed that the SDS binds in an internal cavity that has previously been shown to recognize various general anesthetics. A dissociation constant of 24 9 M at 293 K was determined by isothermal titration calorimetry. SDS binds in this cavity by bending its alkyl tail into a horseshoe shape; the charged SDS head group lies in the opening of the cavity at the protein surface. This crystal structure provides insights into the proteinSDS interactions that give rise to binding and may prove useful in the design of novel SDS-like ligands for some proteins.

  1. Protein binding studies of technetium-99m-labeled phosphine and isocyanide cationic complexes

    SciTech Connect (OSTI)

    Zanelli, G.D.; Cook, N.; Lahiri, A.; Ellison, D.; Webbon, P.; Woolley, G.

    1988-01-01

    Most /sup 99m/Tc/phosphine/isocyanide complexes synthesized to date show preferential uptake by the myocardium of many animal species but not in man. A new complex has been synthesized, (/sup 99m/Tc(DEPE)2(CNR)2), +(DEPIC), where R = t - butyl isocyanide, which in three animal species images the myocardium very well, but in humans it remains primarily in the blood pool. One reason for the difference in the behavior of these complexes in different species could be the characteristics of their binding to plasma proteins. The protein binding characteristics of DEPIC and two other well-known complexes have therefore been studied. Whereas the other complexes bind nonspecifically to many proteins both in animal and human plasma, DEPIC binds almost exclusively to prealbumin in humans but nonspecifically to other proteins in the rabbit. The binding sites in human plasma appear to be those normally occupied by thyroxine on the prealbumin tetramer and these can be blocked by sodium salicylate.

  2. Structures of Adnectin/Protein Complexes Reveal an Expanded Binding Footprint

    SciTech Connect (OSTI)

    Ramamurthy, Vidhyashankar; Krystek, Jr., Stanley R.; Bush, Alexander; Wei, Anzhi; Emanuel, Stuart L.; Gupta, Ruchira Das; Janjua, Ahsen; Cheng, Lin; Murdock, Melissa; Abramczyk, Bozena; Cohen, Daniel; Lin, Zheng; Morin, Paul; Davis, Jonathan H.; Dabritz, Michael; McLaughlin, Douglas C.; Russo, Katie A.; Chao, Ginger; Wright, Martin C.; Jenny, Victoria A.; Engle, Linda J.; Furfine, Eric; Sheriff, Steven

    2014-10-02

    Adnectins are targeted biologics derived from the tenth type III domain of human fibronectin ({sup 10}Fn3), a member of the immunoglobulin superfamily. Target-specific binders are selected from libraries generated by diversifying the three {sup 10}Fn3 loops that are analogous to the complementarity determining regions of antibodies. The crystal structures of two Adnectins were determined, each in complex with its therapeutic target, EGFR or IL-23. Both Adnectins bind different epitopes than those bound by known monoclonal antibodies. Molecular modeling suggests that some of these epitopes might not be accessible to antibodies because of the size and concave shape of the antibody combining site. In addition to interactions from the Adnectin diversified loops, residues from the N terminus and/or the {beta} strands interact with the target proteins in both complexes. Alanine-scanning mutagenesis confirmed the calculated binding energies of these {beta} strand interactions, indicating that these nonloop residues can expand the available binding footprint.

  3. Beta-endorphin and alpha-n-acetyl beta-endorphin; synthesis, conformation and binding parameter

    SciTech Connect (OSTI)

    Lovegren, E.S.

    1986-01-01

    Beta-endorphin (EP) is a 31-residue opioid peptide found in many tissues, including the pituitary, brain and reproductive tract. Alpha-amino-acetyl beta-endorphin (AcEP) was characterized spectroscopically by proton nuclear magnetic resonance (NMR) and circular dichroism in deuterated water and trifluoroethanol (TFE). Both EP and AcEP bind to neuroblastoma N2a cells. This binding was not mediated through opiate receptors, and both peptides seemed to bind at common sites. Ovarian immunoreactive-EP levels were determined for immature and mature rates. These levels were found to be responsive to exogenous gonadotropin treatment in immature animals. A large percentage of the immunoreactive-EP is present in follicular fluid, and most of the endorphin-like peptides were acetylated, as measured by radioimmunoassay. Chromatogaphic analysis suggested at least three EP-like species: EP, a carboxy-terminally cleaved and an amino-terminally acetylated EP.

  4. Theory of the colossal Van-der-Waals binding in soft and hard condensed matter

    E-Print Network [OSTI]

    Mladen Georgiev; Alexander Gochev; Jai Singh

    2005-10-12

    A simple theory is proposed for the dispersive molecular binding of unusually high magnitude due to an enhanced polarizability. Two alternative ways have so far been considered in the literature leading to the polarizability enhancement: (i) a vibronic energy level gap narrowing, as proposed by us with regard to a hypothetical exciton matter, and (ii) a giant electric dipole in a Rydberg state of constituent atoms, as proposed by Gilman with regard to an enigmatic substance building the ball lightning. We now combine the two mechanisms to obtain concrete expressions for the colossal binding energy. The problem is exemplified for a three-level system coupled to the umbrella mode of an ammonia molecule. Other possibilities for the design of enhanced-polarizability molecules are also discussed. The colossal Van-der-Waals binding is most likely to materialize in hard condensed matter and perhaps less so in soft condensed matter.

  5. LINC Complexes Form by Binding of Three KASH Peptides to Domain Interfaces of Trimeric SUN Proteins

    SciTech Connect (OSTI)

    Sosa, Brian A.; Rothballer, Andrea; Kutay, Ulrike; Schwartz, Thomas U.

    2012-08-31

    Linker of nucleoskeleton and cytoskeleton (LINC) complexes span the nuclear envelope and are composed of KASH and SUN proteins residing in the outer and inner nuclear membrane, respectively. LINC formation relies on direct binding of KASH and SUN in the perinuclear space. Thereby, molecular tethers are formed that can transmit forces for chromosome movements, nuclear migration, and anchorage. We present crystal structures of the human SUN2-KASH1/2 complex, the core of the LINC complex. The SUN2 domain is rigidly attached to a trimeric coiled coil that prepositions it to bind three KASH peptides. The peptides bind in three deep and expansive grooves formed between adjacent SUN domains, effectively acting as molecular glue. In addition, a disulfide between conserved cysteines on SUN and KASH covalently links both proteins. The structure provides the basis of LINC complex formation and suggests a model for how LINC complexes might arrange into higher-order clusters to enhance force-coupling.

  6. Crystal Structure of the HP1-EMSY Complex Reveals an Unusual Mode of HP1 Binding

    SciTech Connect (OSTI)

    Huang,Y.; Myers, M.; Xu, R.

    2006-01-01

    Heterochromatin protein-1 (HP1) plays an essential role in both the assembly of higher-order chromatin structure and epigenetic inheritance. The C-terminal chromo shadow domain (CSD) of HP1 is responsible for homodimerization and interaction with a number of chromatin-associated nonhistone proteins, including EMSY, which is a BRCA2-interacting protein that has been implicated in the development of breast and ovarian cancer. We have determined the crystal structure of the HP1{beta} CSD in complex with the N-terminal domain of EMSY at 1.8 Angstroms resolution. Surprisingly, the structure reveals that EMSY is bound by two HP1 CSD homodimers, and the binding sequences differ from the consensus HP1 binding motif PXVXL. This structural information expands our understanding of HP1 binding specificity and provides insights into interactions between HP1 homodimers that are likely to be important for heterochromatin formation.

  7. Evaluation of Two Fluorescent Dyes used in Immunofluorescent Microscopy for the Detection of Proteinaceous Binding Media in Wall Paintings

    E-Print Network [OSTI]

    de Alarcon, Tessa

    2012-01-01

    identify organic binding media within the individual paintorganic components, pigment binder interactions, but also possible variations in paintpaint layers. Spatially resolved analysis of organic

  8. Human Biliverdin Reductase Is a Leucine Zipper-like DNA-binding Protein and Functions in Transcriptional Activation of Heme

    E-Print Network [OSTI]

    Zulfiqar Ahmad

    BVR DNA complex formation; and (e) purified preparations of hBVR or hHO-1 do not bind to DNA with two AP-1

  9. Binding of formyl peptides to Walker 256 carcinosarcoma cells and the chemotactic response of these cells

    SciTech Connect (OSTI)

    Rayner, D.C.; Orr, F.W.; Shiu, R.P.

    1985-05-01

    N-Formylmethionylleucylphenylalanine (fMLP) induces chemotaxis in leukocytes, the response being mediated by peptide binding to a receptor on the plasma membrane. In tumor cells, this peptide has been reported to induce cellular swelling and chemotaxis in vitro and to enhance the localization of circulating tumor cells in vivo. In the Boyden chamber, the authors evaluated the migratory responses of Walker carcinosarcoma 256 cells to varying concentrations of fMLP. Sigmoidal dose-response curves were obtained with the dose of chemotactic factor that elicits a half-maximal chemotactic response of 5.0 +/- 2.5 X 10(-8) M. Checkerboard analysis indicated that these responses were dependent upon a concentration gradient of fMLP with increases in migration of circa 2 to 2.5 times that of random movement. To examine the binding of fMLP, the tumor cells were incubated with 5 X 10(-9) M fML-(/sup 3/H)P in Hanks balanced salt solution. Specific binding (0.5 to 1% of total radioligand, to whole cells inhibited by 5 X 10(-6) M fMLP) approached equilibrium after 4 to 6 h at 4 degrees C and after 6 to 10 h at 22 degrees C. Autoradiographic studies demonstrated heterogeneous binding of the peptide by tumor cells and also showed its intracellular localization. In homogenates of Walker cells prepared in 0.1 M Tris HCl, pH 7.4, with 10 mM MgCl2 and bovine serum albumin (1 mg/ml), specific binding of approximately 0.5% of total fML-(/sup 3/H)P reached equilibrium after 60 min at 4 degrees C. In whole cells and homogenates, binding was reversible by addition of unlabeled fMLP.

  10. Ligand-induced conformational changes in a thermophilic ribose-binding protein

    SciTech Connect (OSTI)

    Cuneo, Matthew J.; Beese, Lorena S.; Hellinga, Homme W.

    2009-05-21

    Members of the periplasmic binding protein (PBP) superfamily are involved in transport and signaling processes in both prokaryotes and eukaryotes. Biological responses are typically mediated by ligand-induced conformational changes in which the binding event is coupled to a hinge-bending motion that brings together two domains in a closed form. In all PBP-mediated biological processes, downstream partners recognize the closed form of the protein. This motion has also been exploited in protein engineering experiments to construct biosensors that transduce ligand binding to a variety of physical signals. Understanding the mechanistic details of PBP conformational changes, both global (hinge bending, twisting, shear movements) and local (rotamer changes, backbone motion), therefore is not only important for understanding their biological function but also for protein engineering experiments. Here we present biochemical characterization and crystal structure determination of the periplasmic ribose-binding protein (RBP) from the hyperthermophile Thermotoga maritima in its ribose-bound and unliganded state. The T. maritima RBP (tmRBP) has 39% sequence identity and is considerably more resistant to thermal denaturation (appTm value is 108 C) than the mesophilic Escherichia coli homolog (ecRBP) (appTm value is 56 C). Polar ligand interactions and ligand-induced global conformational changes are conserved among ecRBP and tmRBP; however local structural rearrangements involving side-chain motions in the ligand-binding site are not conserved. Although the large-scale ligand-induced changes are mediated through similar regions, and are produced by similar backbone movements in tmRBP and ecRBP, the small-scale ligand-induced structural rearrangements differentiate the mesophile and thermophile. This suggests there are mechanistic differences in the manner by which these two proteins bind their ligands and are an example of how two structurally similar proteins utilize different mechanisms to form a ligand-bound state.

  11. Experimental Determination of In-Medium Cluster Binding Energies and Mott Points in Nuclear Matter

    E-Print Network [OSTI]

    K. Hagel; R. Wada; L. Qin; J. B. Natowitz; S. Shlomo; A. Bonasera; G. Rpke; S. Typel; Z. Chen; M. Huang; J. Wang; H. Zheng; S. Kowalski; C. Bottosso; M. Barbui; M. R. D. Rodrigues; K. Schmidt; D. Fabris; M. Lunardon; S. Moretto; G. Nebbia; S. Pesente; V. Rizzi; G. Viesti; M. Cinausero; G. Prete; T. Keutgen; Y. El Masri; Z. Majka

    2012-03-20

    In medium binding energies and Mott points for $d$, $t$, $^3$He and $\\alpha$ clusters in low density nuclear matter have been determined at specific combinations of temperature and density in low density nuclear matter produced in collisions of 47$A$ MeV $^{40}$Ar and $^{64}$Zn projectiles with $^{112}$Sn and $^{124}$Sn target nuclei. The experimentally derived values of the in medium modified binding energies are in good agreement with recent theoretical predictions based upon the implementation of Pauli blocking effects in a quantum statistical approach.

  12. Expression levels of MHC class I molecules are inversely correlated with promiscuity of peptide binding

    E-Print Network [OSTI]

    Chappell, Paul E.; Meziane, El Kahina; Harrison, Michael; Magiera, ?ukasz; Hermann, Clemens; Mears, Laura; Wrobel, Antoni G.; Durant, Charlotte; Nielsen, Lise Lotte; Buus, Sren; Ternette, Nicola; Mwangi, William; Butter, Colin; Nair, Venugopal; Ahyee, Trudy; Duggleby, Richard; Madrigal, Alejandro; Roversi, Pietro; Lea, Susan M.; Kaufman, Jim

    2015-04-10

    in and around the beginning of the groove and reveals Figure 4. Structures of BF2*2101 with different peptides show several modes of promiscuous binding through remodelling of the binding site. Left panels, top down view with peptide as sticks (N... residues. Upper panels, side view from ?2 domain side with peptide as sticks (N-terminus of peptide to the left; carbon atoms of peptide, yellow; carbon atoms of class I molecule, white; nitrogen atoms, blue; oxygen atoms, red; hydrogen bonds, dotted lines...

  13. Photoelectron Spectroscopy and Theoretical Studies of Anion-pi Interactions: Binding Strength and Anion Specificity

    SciTech Connect (OSTI)

    Zhang, Jian; Zhou, Bin; Sun, Zhenrong; Wang, Xue B.

    2015-01-01

    Proposed in theory and confirmed to exist, anion? interactions have been recognized as new and important non-covalent binding forces. Despite extensive theoretical studies, numerous crystal structural identifications, and a plethora of solution phase investigations, intrinsic anion? interaction strengths that are free from complications of condensed phases environments, have not been directly measured in the gas phase. Herein we present a joint photoelectron spectroscopic and theoretical study on this subject, in which tetraoxacalix[2]arene[2]triazine 1, an electron-deficient and cavity self-tunable macrocyclic was used as a charge-neutral molecular host to probe its interactions with a series of anions with distinctly different shapes and charge states (spherical halides Cl?, Br?, I?, linear thiocyanate SCN?, trigonal planar nitrate NO??, pyramidic iodate IO??, and tetrahedral sulfate SO??). The binding energies of the resultant gaseous 1:1 complexes (1Cl?,1Br?, 1I?, 1SCN?, 1NO??, 1IO?? and 1SO??) were directly measured experimentally, exhibiting substantial non-covalent interactions with pronounced anion specific effects. The binding strengths of Cl?, NO??, IO?? with 1 are found to be strongest among all singly charged anions, amounting to ca. 30 kcal/mol, but only about 40% of that between 1 and SO??. Quantum chemical calculations reveal that all anions reside in the center of the cavity of 1 with anion? binding motif in the complexes optimized structures, where 1 is seen to be able to self-regulate its cavity structure to accommodate anions of different geometries and three-dimensional shapes. Electron density surface and natural bond orbital charge distribution analysis further support anion? binding formation. The calculated binding energies of the anions and 1 nicely reproduce the experimentally estimated electron binding energy increase. This work illustrates that size-selective photoelectron spectroscopy combined with theoretical calculations represent a powerful technique to probe intrinsic anion? interactions and has potential to provide quantitative guest-host molecular binding strengths and unravel fundamental insights in specific anion recognitions.

  14. Evaluation of Uranyl Photocleavage as a Probe to Monitor Ion Binding and Flexibility in RNAs

    E-Print Network [OSTI]

    Westhof, Eric

    Evaluation of Uranyl Photocleavage as a Probe to Monitor Ion Binding and Flexibility in RNAs Dolly uranyl photocleavage as a tool to identify and characterize structural and dynamic properties in RNA, we compared uranyl cleavage sites in ve RNA molecules with known X-ray struc- tures, namely the hammerhead

  15. De Novo Design and Spectroscopic Characterization of a Dinucleating Copper-Binding Pentadecapeptide

    E-Print Network [OSTI]

    Cammers, Arthur

    of aqueous solutions of Ac-WGHGHGH- GPGHGHGH-NH2 (HGP) indicates that copper(II) binds to the peptide to form a 2:1 Cu2+ /HGP complex with four nitrogen atoms in the copper coordination environment. Electron and imidazole nitrogen donors. Circular dichroism data show that HGP is unbound below pH 5.5 and is copper

  16. DNA Profiling Using Solid-State Nanopores: Detection of DNA-Binding

    E-Print Network [OSTI]

    Meller, Amit

    a 3.5 nm pore results from threading of a dye-intercalated DNA molecule, as compared to the typical for drug development, necessitating new in vitro methods for rapid and low-cost assessment of the binding molecules, which give the DNA/intercalator complex a bulkier structure than that of native DNA. Furthermore

  17. Flow-Through vs Flow-Over: Analysis of Transport and Binding in Nanohole Array Plasmonic

    E-Print Network [OSTI]

    Brolo, Alexandre G.

    Flow-Through vs Flow-Over: Analysis of Transport and Binding in Nanohole Array Plasmonic Biosensors of flow-through nanohole sensing, as compared to the established flow-over format, through scaling and analytical response. The additional benefit offered by flow- through operation is, however, a complex

  18. Heart- and liver-type fatty acid binding proteins in lipid and glucose metabolism

    E-Print Network [OSTI]

    Erol, Erdal

    2004-11-15

    Heart-type Fatty Acid-Binding Protein (H-FABP) is required for high rates of skeletal muscle long chain fatty acid (LCFA) oxidation and esterification. Here we assessed whether H-FABP affects soleus muscle glucose uptake when measured in vitro...

  19. Human Cellular Retinaldehyde-Binding Protein Has Secondary Thermal 9-cis-Retinal Isomerase Activity

    E-Print Network [OSTI]

    Palczewski, Krzysztof

    Human Cellular Retinaldehyde-Binding Protein Has Secondary Thermal 9-cis-Retinal Isomerase Activity molecules in both CRALBP-assisted specificity toward 9-cis-retinal and its thermal isomerase activity opsin receptor molecules into photosensitive retinoid pigments of the eye. We report a thermal secondary

  20. Vertebrate Proteins Related to Drosophila Naked Cuticle Bind Dishevelled and Antagonize

    E-Print Network [OSTI]

    Scott, Matthew

    Vertebrate Proteins Related to Drosophila Naked Cuticle Bind Dishevelled and Antagonize Wnt severe segmentation defects. The Drosophila segment polarity gene naked cuticle (nkd) encodes an EF hand counterpart, may act as inducible antagonists of Wnt signals. 2001 Academic Press Key Words: naked cuticle

  1. Context-Sensitive Binding by the Laminar Circuits of V1 and V2

    E-Print Network [OSTI]

    Grossberg, Stephen

    Context-Sensitive Binding by the Laminar Circuits of V1 and V2: A Unified Model of Perceptual A detailed neural model is presented of how the laminar circuits of visual cortical areas V1 and V2 implement specific laminar circuits allow the responses of visual cortical neurons to be determined not only

  2. Detection of growth factor binding to gelatin and heparin using a photonic crystal optical biosensor

    E-Print Network [OSTI]

    Cunningham, Brian

    Detection of growth factor binding to gelatin and heparin using a photonic crystal optical: Photonic crystal biosensor Label-free Gelatin Heparin Growth factor Drugcarrier Drugcarrier interactions timed release. A novel photonic crystal biosensor was used to investigate a gelatinprotein controlled

  3. Energy Requirement for Lignocellulosic Feedstock Densifications in Relation to Particle Physical Properties, Preheating, and Binding

    E-Print Network [OSTI]

    Properties, Preheating, and Binding Agents Zewei Miao,, Tony E. Grift,*,, Alan C. Hansen,, and K. C. Ting the energy consumption of herbaceous feedstock compression in relation to particle physical properties-combustion with coal or direct combustion for domestic heating, steam, and electricity generation.13-17 In recent years

  4. Sequence Convergence in the Peptide-Binding Region of Primate and Rodent MHC Class Ib Molecules

    E-Print Network [OSTI]

    Kumar, Sudhir

    Sequence Convergence in the Peptide-Binding Region of Primate and Rodent MHC Class Ib Molecules polymorphic class Ia genes, the major histocompatibility complex (MHC) of placental mammals includes class Ib. The functional importance of class Ib genes as well as their actual function has long been controversial

  5. Afamin Is a Novel Human Vitamin E-Binding Glycoprotein Characterization and In Vitro Expression

    E-Print Network [OSTI]

    Afamin Is a Novel Human Vitamin E-Binding Glycoprotein Characterization and In Vitro Expression of Molecular Pathology, Vienna, Austria Received January 23, 2005 Hydrophobic vitamins are transported in human for vitamin E, which plays a crucial role in protecting against oxidative damage and disease. We report here

  6. Biochemical regulation of circadian 2-125 I-iodomelatonin binding in chick optic tectum

    E-Print Network [OSTI]

    Vercesi, Haydee Margarita

    1994-01-01

    /mg) and low values in late SN (CT22: 3.76 fmol/mg). Conversely, autoradiography showed a binding rhythm with high values only during mid and late SD (average of 5.01 fmol/mg at CT6 and CT10) and low values in SN (an average of 0. 69 fmol/mg from CT 1 4...

  7. Methanobactin: a copper binding compound having antibiotic and antioxidant activity isolated from methanotrophic bacteria

    DOE Patents [OSTI]

    DiSpirito, Alan A. (Ames, IA); Zahn, James A. (Harbor Beach, MI); Graham, David W. (Lawrence, KS); Kim, Hyung J. (St. Paul, MN); Alterman, Michail (Lawrence, KS); Larive, Cynthia (Lawrence, KS)

    2007-04-03

    A means and method for treating bacterial infection, providing antioxidant activity, and chelating copper using a copper binding compound produced by methanotrophic bacteria is described. The compound, known as methanobactin, is the first of a new class of antibiotics having gram-positive activity. Methanobactin has been sequenced, and its structural formula determined.

  8. Osmotic stress, crowding, preferential hydration, and binding: A comparison of perspectives

    E-Print Network [OSTI]

    Rau, Don C.

    Osmotic stress, crowding, preferential hydration, and binding: A comparison of perspectives V. A, osmotic stress, preferential interaction, and crowding, to describe the indirect effect of solutes of osmotic stress (1) has been used to measure the changes in macromolecular hydration for several reactions

  9. Thermodynamics of Antimicrobial Lipopeptide Binding to Membranes: Origins of Affinity and Selectivity

    E-Print Network [OSTI]

    , using coarse-grained molecular-dynamics simulations and free energy methods to uncover membranes, which tend to be en- riched in anionic lipids relative to animals, whereas the amphipathic structure stabilizes binding in the membrane- water interface. Several models have been proposed to explain

  10. In Silico Transfer of Ligand Binding Function between Structurally Analogous Proteins

    E-Print Network [OSTI]

    In Silico Transfer of Ligand Binding Function between Structurally Analogous Proteins Ali Awan #12;Introduction One of the major goals of biotechnology is the deliberate modification of proteins, or protein in scientific studies, in which protein engineering has helped further our knowledge of proteins

  11. IEEE JOURNAL OF SELECTED TOPICS IN QUANTUM ELECTRONICS 1 High Specificity Binding of Lectins to

    E-Print Network [OSTI]

    Dagenais, Mario

    IEEE JOURNAL OF SELECTED TOPICS IN QUANTUM ELECTRONICS 1 High Specificity Binding of Lectins, IEEE, Mario Dagenais, Senior Member, IEEE, Matthew T. Hurley, and Philip DeShong Abstract are available online at http://ieeexplore.ieee.org. Digital Object Identifier 10.1109/JSTQE.2009

  12. Nuclear Physics A 611 ( 1996) 484-513 Mesonic and binding contributions to the EMC

    E-Print Network [OSTI]

    Fernndez de Crdoba, Pedro

    NUCLEAR PHYSICS A Nuclear Physics A 611 ( 1996) 484-513 Mesonic and binding contributions November 1995; revised 30 July 1996 Abstract We revise the conventional nuclear effects of Fermi motion for an interacting Fermi sea and the local density approximation to translate results from nuclear matter to finite

  13. A new protein folding screen: Application to the ligand binding domains of a glutamate and kainate

    E-Print Network [OSTI]

    Lebendiker, Mario

    A new protein folding screen: Application to the ligand binding domains of a glutamate and kainate of determining and evaluating protein folding conditions, we have designed a new fractional factorial protein folding screen. The screen includes 12 factors shown by previous experiments to enhance protein folding

  14. A ligand-binding pocket in the dengue virus envelope glycoprotein

    E-Print Network [OSTI]

    Harrison, Stephen C.

    A ligand-binding pocket in the dengue virus envelope glycoprotein Yorgo Modis*, Steven Ogata Heights Drive, Suite 200, Aiea, HI 96701 Contributed by Stephen C. Harrison, April 14, 2003 Dengue virus by membrane fusion. A crystal structure of the soluble ectodomain of E from dengue virus type 2 reveals

  15. How Cations Can Assist DNase I in DNA Binding and Marc Gueroult1,2

    E-Print Network [OSTI]

    How Cations Can Assist DNase I in DNA Binding and Hydrolysis Marc Gueroult1,2 , Daniel Picot3 , Josephine Abi-Ghanem2 , Brigitte Hartmann2 *, Marc Baaden1 * 1 CNRS UPR 9080, Institut de Biologie: Marc Baaden thanks the French National Research Agency for funding (Grants ANR-06-PCVI-0025 and ANR-07

  16. Vimentin Binding to Phosphorylated Erk Sterically Hinders Enzymatic Dephosphorylation of the Kinase

    E-Print Network [OSTI]

    Fainzilber, Michael

    Vimentin Binding to Phosphorylated Erk Sterically Hinders Enzymatic Dephosphorylation of the Kinase with phosphorylated Erk1 and Erk2 MAP kinases (pErk) in injured sciatic nerve, thus linking pErk to a signaling for this interaction, which explains how pErk is protected from dephos- phorylation while bound to vimentin. Pull

  17. Computational Study of Propylene and Propane Binding in Metal-Organic Frameworks Containing Highly Exposed Cu+

    E-Print Network [OSTI]

    Computational Study of Propylene and Propane Binding in Metal- Organic Frameworks Containing Highly than propane, suggesting their utility in adsorption separations. The nature of the propylene challenging problems in the field of separations is the separation of propane/propylene mixtures. Propylene

  18. Adhesion of membranes via receptor-ligand complexes: Domain formation, binding cooperativity, and active processes

    E-Print Network [OSTI]

    Thomas R. Weikl; Mesfin Asfaw; Heinrich Krobath; Bartosz Rozycki; Reinhard Lipowsky

    2009-06-09

    Cell membranes interact via anchored receptor and ligand molecules. Central questions on cell adhesion concern the binding affinity of these membrane-anchored molecules, the mechanisms leading to the receptor-ligand domains observed during adhesion, and the role of cytoskeletal and other active processes. In this review, these questions are addressed from a theoretical perspective. We focus on models in which the membranes are described as elastic sheets, and the receptors and ligands as anchored molecules. In these models, the thermal membrane roughness on the nanometer scale leads to a cooperative binding of anchored receptor and ligand molecules, since the receptor-ligand binding smoothens out the membranes and facilitates the formation of additional bonds. Patterns of receptor domains observed in Monte Carlo simulations point towards a joint role of spontaneous and active processes in cell adhesion. The interactions mediated by the receptors and ligand molecules can be characterized by effective membrane adhesion potentials that depend on the concentrations and binding energies of the molecules.

  19. HYDROGEN ATOMS IN NEUTRON STAR ATMOSPHERES: ANALYTICAL APPROXIMATIONS FOR BINDING ENERGIES

    E-Print Network [OSTI]

    HYDROGEN ATOMS IN NEUTRON STAR ATMOSPHERES: ANALYTICAL APPROXIMATIONS FOR BINDING ENERGIES Atoms energies of the hydrogen atom arbitrarily moving in a magnetic field typical of neutron stars, 300 Ÿ fl Ÿ the spectrum of outgoing thermal radiation, likely consists of hydrogen, the most abundant element

  20. van der Waals density functional study of CO2 binding in zeolitic imidazolate frameworks

    E-Print Network [OSTI]

    Ray, Keith G.; Olmsted, David; He, Ning; Houndonougbo, Yao; Laird, Brian Bostian; Asta, Mark

    2012-02-06

    The van der Waals density functional (vdW-DF) formalism is employed in a study of the binding energetics for CO2 in a set of five zeolitic imidazolate framework (ZIF) compounds. The ZIF structures investigated share the same RHO-type zeolite...

  1. Many sequence-specific chromatin modifying protein-binding motifs show strong positional

    E-Print Network [OSTI]

    Mario-Ramrez, Leonardo

    for Biotechnology Information, National Library of Medicine, National Institutes of Health, 8900 Rockville Pike Marin~ o-Ramirez3 and David Landsman1, * 1 Computational Biology Branch, National Center binding sites, nucleosomes play an indirect role in regulating gene expression (47). However, this raises

  2. Thermodynamics of Oligoarginines Binding to RNA and DNA David P. Mascotti and Timothy M. Lohman*

    E-Print Network [OSTI]

    Lohman, Timothy M.

    Thermodynamics of Oligoarginines Binding to RNA and DNA David P. Mascotti and Timothy M. Lohman basis for the stabilities of these complexes requires information on the thermodynamics (thermodynamics) of well-defined model peptides to nucleic acids [for a review, see Lohman and Mascotti (1992a

  3. Atomistic Modeling of Macromolecular Crowding Predicts Modest Increases in Protein Folding and Binding Stability

    E-Print Network [OSTI]

    Weston, Ken

    Atomistic Modeling of Macromolecular Crowding Predicts Modest Increases in Protein Folding that macromolecular crowding can increase protein folding stability, but depending on details of the models (e.g., how on the effects of macro- molecular crowding on protein folding and binding stability has been reached. Crowders

  4. Optimization of Virus Imprinting Methods To Improve Selectivity and Reduce Nonspecific Binding

    E-Print Network [OSTI]

    Rubloff, Gary W.

    Optimization of Virus Imprinting Methods To Improve Selectivity and Reduce Nonspecific Binding such as viruses are imprinted, special consideration must be taken to ensure the formation of complementary and release of the virus template after cross-linking. In this study, tobacco mosaic virus (TMV) was used

  5. Hydrogen-impurity binding energy in vanadium and niobium A. Mokrani and C. Demangeat

    E-Print Network [OSTI]

    Boyer, Edmond

    2243 Hydrogen-impurity binding energy in vanadium and niobium A. Mokrani and C. Demangeat IPCMS, UM by the hydrogen) contribution, ii) the band structure contribution, iii) the electron-electron interaction without. Strong H-H repulsion is observed when the hydrogen atoms are at first nearest neighbouring positions

  6. Biochemical characterization of Cdc6/Orc1 binding to the replication origin of the euryarchaeon

    E-Print Network [OSTI]

    Berger, James M.

    Biochemical characterization of Cdc6/Orc1 binding to the replication origin of the euryarchaeon (Cdc6)/Origin Replication Complex subunit 1 (Orc1) proteins share sequence homology with eukaryotic DNA under- stand whether Cdc6/Orc1 functions in an eukaryotic or bacterial-like manner, we have

  7. INTERNATIONAL JOURNAL OF SPORT BIOMECHANICS, 1992,8,331-349 A New Electromechanical Ski Binding

    E-Print Network [OSTI]

    With Release Sensitivity to Torsion and Bending Moments Transmitted by the Leg Rick Neptune and Maury L. Hull This paper describes the design of a new electromechanical ski binding whereby release in both twist and forward bending is controlled electronically and the release level in twist is modulated electronically

  8. Structure of the Escherichia coli Phosphonate Binding Protein PhnD and Rationally Optimized Phosphonate Biosensors

    SciTech Connect (OSTI)

    Alicea, Ismael; Marvin, Jonathan S.; Miklos, Aleksandr E.; Ellington, Andrew D.; Looger, Loren L.; Schreiter, Eric R.

    2012-09-17

    The phnD gene of Escherichia coli encodes the periplasmic binding protein of the phosphonate (Pn) uptake and utilization pathway. We have crystallized and determined structures of E. coli PhnD (EcPhnD) in the absence of ligand and in complex with the environmentally abundant 2-aminoethylphosphonate (2AEP). Similar to other bacterial periplasmic binding proteins, 2AEP binds near the center of mass of EcPhnD in a cleft formed between two lobes. Comparison of the open, unliganded structure with the closed 2AEP-bound structure shows that the two lobes pivot around a hinge by {approx}70{sup o} between the two states. Extensive hydrogen bonding and electrostatic interactions stabilize 2AEP, which binds to EcPhnD with low nanomolar affinity. These structures provide insight into Pn uptake by bacteria and facilitated the rational design of high signal-to-noise Pn biosensors based on both coupled small-molecule dyes and autocatalytic fluorescent proteins.

  9. A Bound on Binding Energies and Mass Renormalization in Models of Quantum

    E-Print Network [OSTI]

    A Bound on Binding Energies and Mass Renormalization in Models of Quantum Electrodynamics Elliott H: the #12;rst uses the kinetic energy (p + eA(x)) 2 and the second uses the Pauli-Fierz energy (p + eA(x)) 2 + e#27; #1; B(x). The third, no-pair model, is relativistic and replaces the kinetic energy

  10. Structural Basis for p300 Taz2-p53 TAD1 Binding and Modulation by Phosphorylation

    E-Print Network [OSTI]

    Laboratory of Biochemistry and Molecular Biology 2Laboratory of Cell Biology National Cancer Institute, NIH, Bethesda, MD 20892, USA 3Macromolecular Crystallography Laboratory, National Cancer Institute at Frederick. Among those domains are two transcriptional adaptor zinc-binding (Taz) domains, Taz1 (C/H1) and Taz2 (C

  11. Acetylation curtails nucleosome binding, not stable nucleosome remodeling, by FoxO1

    SciTech Connect (OSTI)

    Hatta, M.; Liu, F. [Department of Cell Biology, Neurobiology, and Anatomy, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226 (United States); Cirillo, L.A. [Department of Cell Biology, Neurobiology, and Anatomy, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226 (United States)], E-mail: lcirillo@mcw.edu

    2009-02-20

    Transcriptional activity of FoxO factors is controlled through the actions of multiple growth factors signaling through protein kinase B, whereby phosphorylation of FoxO factors inhibits FoxO-mediated transactivation by promoting nuclear export. Phosphorylation of FoxO factors is enhanced by p300-mediated acetylation, which decreases their affinity for DNA. The negative effect of acetylation on FoxO DNA binding, together with nuclear FoxO mobility, is eliminated by over-expression of the de-acetylase Sirt1, suggesting that acetylation mobilizes FoxO factors in chromatin for inducible gene expression. Here, we show that acetylation significantly curtails the affinity of FoxO1 for its binding sites in nucleosomal DNA but has no effect on either stable nucleosome binding or remodeling by this factor. We suggest that, while acetylation provides a first, essential step toward mobilizing FoxO factors for inducible gene repression, additional mechanisms exist for overcoming their inherent capacity to stably bind and remodel nuclear chromatin.

  12. Ligand binding and activation of the Ah receptor Michael S. Denison a,

    E-Print Network [OSTI]

    Baldwin, Enoch

    receptor; 2,3,7,8-Tetrachlorodibenzo-p-dioxin; TCDD; Dioxin; Homology model; Ligand binding domain; PAH, polycyclic aromatic hydrocarbon; PAS, Per/Arnt/Sim; PCDD, polychlorinated dibenzo-p-dioxin; PGG2, prostaglandin G2 PYP, photoactive yellow protein; TCDD, 2,3,7,8-tetrachlorodibenzo-p-dioxin; TRP

  13. Identification of an octamer-binding site in the human kappa light-chain enhancer

    SciTech Connect (OSTI)

    Nelms, K.; Van Ness, B. (Institute of Human Genetics and Dept. of Biochemistry, Univ. of Minnesota, Minneapolis (MN))

    1990-07-01

    Octamer motifs contribute to the function and tissue specificity of immunoglobulin heavy- and light-chain gene promoters and the heavy-chain enhancer. A variant octamer-binding site within a conserved region of the human kappa light-chain gene enhancer which contributes to the function of this enhancer has been identified.

  14. Kits and methods of detection using cellulose binding domain fusion proteins

    DOE Patents [OSTI]

    Shoseyov, Oded (Karmey Yosef, IL)

    1998-01-01

    A cellulose binding domain (CBD) having a high affinity for crystalline cellulose and chitin is disclosed, along with methods for the molecular cloning and recombinant production thereof. Fusion products comprising the CBD and a second protein are likewise described. A wide range of applications are contemplated for both the CBD and the fusion products, including drug delivery, affinity separations, and diagnostic techniques.

  15. Kits and methods of detection using cellulose binding domain fusion proteins

    DOE Patents [OSTI]

    Shoseyov, O.; Yosef, K.

    1998-04-14

    A cellulose binding domain (CBD) having a high affinity for crystalline cellulose and chitin is disclosed, along with methods for the molecular cloning and recombinant production. Fusion products comprising the CBD and a second protein are likewise described. A wide range of applications are contemplated for both the CBD and the fusion products, including drug delivery, affinity separations, and diagnostic techniques. 16 figs.

  16. Distribution of binding energies of a water molecule in the water liquid-vapor interface

    SciTech Connect (OSTI)

    Chempath, Shaji [Los Alamos National Laboratory; Pratt, Lawrence R [TULANE UNIV

    2008-01-01

    Distributions of binding energies of a water molecule in the water liquid-vapor interface are obtained on the basis of molecular simulation with the SPC/E model of water. These binding energies together with the observed interfacial density profile are used to test a minimally conditioned Gaussian quasi-chemical statistical thermodynamic theory. Binding energy distributions for water molecules in that interfacial region clearly exhibit a composite structure. A minimally conditioned Gaussian quasi-chemical model that is accurate for the free energy of bulk liquid water breaks down for water molecules in the liquid-vapor interfacial region. This breakdown is associated with the fact that this minimally conditioned Gaussian model would be inaccurate for the statistical thermodynamics of a dilute gas. Aggressive conditioning greatly improves the performance of that Gaussian quasi-chemical model. The analogy between the Gaussian quasi-chemical model and dielectric models of hydration free energies suggests that naive dielectric models without the conditioning features of quasi-chemical theory will be unreliable for these interfacial problems. Multi-Gaussian models that address the composite nature of the binding energy distributions observed in the interfacial region might provide a mechanism for correcting dielectric models for practical applications.

  17. Relative energetics and structural properties of zirconia using a self-consistent tight-binding model

    E-Print Network [OSTI]

    Paxton, Anthony T.

    Relative energetics and structural properties of zirconia using a self-consistent tight We describe an empirical, self-consistent, orthogonal tight-binding model for zirconia, which allows orders the zero temperature energies of all zirconia polymorphs. The Zr-O matrix elements

  18. Estimating ProteinLigand Binding Free Energy: Atomic Solvation Parameters for Partition Coefficient and

    E-Print Network [OSTI]

    Luhua, Lai

    Estimating ProteinLigand Binding Free Energy: Atomic Solvation Parameters for Partition Coefficient and Solvation Free Energy Calculation Jianfeng Pei,1,2 Qi Wang,1,2 Jiaju Zhou,3 and Luhua Lai1 free energy and the correct scoring in docking studies. We have developed a new solvation energy

  19. STAR/MPI: Binding a Parallel Library to Interactive Symbolic Algebra Systems

    E-Print Network [OSTI]

    Cooperman, Gene

    by layering it on top of existing parallel software packages, any symbolic algebra systems integrating STARSTAR/MPI: Binding a Parallel Library to Interactive Symbolic Algebra Systems Gene Cooperman 1 gene of symbolic algebra systems have felt the need for greater CPU power. Yet few of them have ventured

  20. Inhibition of In Vitro Nuclear Transport by a Lectin that Binds to Nuclear Pores

    E-Print Network [OSTI]

    Forbes, Douglass

    Californiaat San Diego, LaJolla, California92093 Abstract. Selective transport of proteins is a major mechanismInhibition of In Vitro Nuclear Transport by a Lectin that Binds to Nuclear Pores Deborah R. Finlay to investigate the molecular mechanism of nuclear transport, we used an in vitro transport system com- posed

  1. Tumor necrosis factor: specific binding and internalization in sensitive and resistant cells

    SciTech Connect (OSTI)

    Tsujimoto, M.; Yip, Y.K.; Vilcek, J.

    1985-11-01

    Highly purified, Escherichia coli-derived recombinant human tumor necrosis factor (TNF) was labeled with /sup 125/I and employed to determine receptor binding, internalization, and intracellular degradation in murine L929 cells (highly sensitive to the cytotoxic action of TNF) and in diploid human FS-4 cells (resistant to TNF cytotoxicity). /sup 125/I-labeled TNF bound specifically to high-affinity receptors on both L929 and FS-4 cells. Scatchard analysis of the binding data indicated the presence of 2200 binding sites per L929 cell and 7500 binding sites per FS-4 cell. The calculated dissociation constants are 6.1 x 10/sup -10/ M and 3.2 x 10/sup -10/ M for L929 and FS-4 cells, respectively. In both L929 and FS-4 cells, incubation at 37/sup 0/C resulted in a rapid internalization of the bulk of the cell-bound TNF, followed by the appearance of trichloroacetic acid-soluble /sup 125/I radioactivity in the tissue culture medium, due to degradation of TNF. Degradation but not cellular uptake of TNF was inhibited in the presence of chloroquine (an inhibitor of lysosomal proteases) in both L929 and FS-4 cells, suggesting that degradation occurs intracellularly, probably within lysosomes. These results show that resistance of FS-4 cells to TNF cytotoxicity is not due to a lack of receptors or their inability to internalize and degrade TNF.

  2. Modulation of the Toxicity and Macromolecular Binding of Benzene Metabolites by NAD(P)H:Quinone

    E-Print Network [OSTI]

    California at Berkeley, University of

    Articles Modulation of the Toxicity and Macromolecular Binding of Benzene Metabolites by NAD, San Francisco, California 94143-0560 Received April 17, 1998 Benzene is oxidized in the liver of benzene metabolite toxicity. NQO1 expression reduced a class of hydroquinone- and benzenetriol-induced DNA

  3. Statistical model for receptor-ligand binding thermodynamics Marc Thilo Figge*

    E-Print Network [OSTI]

    acids that belong to different complementarity classes. Based on empirical data, amino ac- ids the receptor-ligand overlap region con- sists typically of 100 amino acids. The receptor-ligand bind- ing area acids 3 and in another experiment to involve 14 amino acids distributed over three separate linear

  4. Identifying Affinity Classes of Inorganic Materials Binding Sequences via a Graph-based Model

    E-Print Network [OSTI]

    Buffalo, State University of New York

    material. We first generate a large set of simulated peptide sequences based on an amino acid transition peptide sequences, which are usually 7-14 amino acids long, are differentiated from other polypeptides1 Identifying Affinity Classes of Inorganic Materials Binding Sequences via a Graph-based Model Nan

  5. Comparing Kernels For Predicting Protein Binding Sites From Amino Acid Sequence

    E-Print Network [OSTI]

    Honavar, Vasant

    in on all three tasks, with the substitution kernel based on amino acid substitution matrices that take into account structural or evolutionary conservation or physicochemical properties of amino acids yields modestComparing Kernels For Predicting Protein Binding Sites From Amino Acid Sequence Feihong Wu1

  6. Fluoroalkyl and Alkyl Chains Have Similar Hydrophobicities in Binding to the Hydrophobic Wall of Carbonic Anhydrase

    SciTech Connect (OSTI)

    J Mecinovic; P Snyder; K Mirica; S Bai; E Mack; R Kwant; D Moustakas; A Heroux; G Whitesides

    2011-12-31

    The hydrophobic effect, the free-energetically favorable association of nonpolar solutes in water, makes a dominant contribution to binding of many systems of ligands and proteins. The objective of this study was to examine the hydrophobic effect in biomolecular recognition using two chemically different but structurally similar hydrophobic groups, aliphatic hydrocarbons and aliphatic fluorocarbons, and to determine whether the hydrophobicity of the two groups could be distinguished by thermodynamic and biostructural analysis. This paper uses isothermal titration calorimetry (ITC) to examine the thermodynamics of binding of benzenesulfonamides substituted in the para position with alkyl and fluoroalkyl chains (H{sub 2}NSO{sub 2}C{sub 6}H{sub 4}-CONHCH{sub 2}(CX{sub 2}){sub n}CX{sub 3}, n = 0-4, X = H, F) to human carbonic anhydrase II (HCA II). Both alkyl and fluoroalkyl substituents contribute favorably to the enthalpy and the entropy of binding; these contributions increase as the length of chain of the hydrophobic substituent increases. Crystallography of the protein-ligand complexes indicates that the benzenesulfonamide groups of all ligands examined bind with similar geometry, that the tail groups associate with the hydrophobic wall of HCA II (which is made up of the side chains of residues Phe131, Val135, Pro202, and Leu204), and that the structure of the protein is indistinguishable for all but one of the complexes (the longest member of the fluoroalkyl series). Analysis of the thermodynamics of binding as a function of structure is compatible with the hypothesis that hydrophobic binding of both alkyl and fluoroalkyl chains to hydrophobic surface of carbonic anhydrase is due primarily to the release of nonoptimally hydrogen-bonded water molecules that hydrate the binding cavity (including the hydrophobic wall) of HCA II and to the release of water molecules that surround the hydrophobic chain of the ligands. This study defines the balance of enthalpic and entropic contributions to the hydrophobic effect in this representative system of protein and ligand: hydrophobic interactions, here, seem to comprise approximately equal contributions from enthalpy (plausibly from strengthening networks of hydrogen bonds among molecules of water) and entropy (from release of water from configurationally restricted positions).

  7. Orientation-dependent binding energy of graphene on palladium Branden B. Kappes, Abbas Ebnonnasir, Suneel Kodambaka, and Cristian V. Ciobanu

    E-Print Network [OSTI]

    Ciobanu, Cristian

    Orientation-dependent binding energy of graphene on palladium Branden B. Kappes, Abbas Ebnonnasir;Orientation-dependent binding energy of graphene on palladium Branden B. Kappes,1,a) Abbas Ebnonnasir,1 Suneel on Pd(111) for a range of in-plane orientations and show that the atomic- level carbonpalladium

  8. 614 Biochemistry 1994, 33, 614-621 Hydroxyl Radical Footprinting of Calicheamicin. Relationship of DNA Binding to

    E-Print Network [OSTI]

    Tullius, Thomas D.

    614 Biochemistry 1994, 33, 614-621 Hydroxyl Radical Footprinting of Calicheamicin. Relationship the method of hydroxyl radical footprinting. The drug binding sites determined in this way were compared sites of calicheamicin binding, determined by the hydroxyl radical footprinting method (Tullius

  9. 10094 Biochemistry 1995,34, 10094-10100 Characterization of Metal Binding by a Designed Protein: Single Ligand

    E-Print Network [OSTI]

    Mochrie, Simon

    10094 Biochemistry 1995,34, 10094-10100 Characterization of Metal Binding by a Designed Protein of Molecular Biophysics 13Biochemistry, Yale University, 266 Whitney Avenue, New Haven, Connecticut 06520)-binding site in the de novo designed protein ZQ [Regan, L., & Clarke, N. D. (1990) Biochemistry 29, 108781

  10. PEA-15 Binding to ERK1/2 MAPKs Is Required for Its Modulation of Integrin Activation*

    E-Print Network [OSTI]

    Ramos, Joe W.

    PEA-15 Binding to ERK1/2 MAPKs Is Required for Its Modulation of Integrin Activation* Received and 2 (ERK1/2). However, bulk ERK1/2 activation does not correlate with suppression. PEA-15 reverses suppression of integrin activation and binds ERK1/2. Here we report that PEA-15 reversal of integrin

  11. Theory of Free Energy and Entropy in Noncovalent Binding HUAN-XIANG ZHOU AND MICHAEL K. GILSON

    E-Print Network [OSTI]

    Weston, Ken

    S1 Theory of Free Energy and Entropy in Noncovalent Binding HUAN-XIANG ZHOU AND MICHAEL K. GILSON 1 in a form that supports the present formulation of the theory of noncovalent binding. The free energy, F, provides a measure of the stability of a system at thermal equilibrium: the lower the free energy

  12. Omeprazole Stimulates the Induction of Human Insulin-Like Growth Factor Binding Protein-1 through Aryl Hydrocarbon

    E-Print Network [OSTI]

    Perdew, Gary

    gene reveals the presence of an aryl hydrocarbon binding/dioxin response element (DRE). Quan- titative factor capable of binding dioxin response elements (DRE) and initiating transcription of Ah,3,7,8-tetrachlorodibenzo-p- dioxin (TCDD) being the prototypical example; polycyclic aromatic hydrocarbons, e.g., benzo

  13. Effect of primer binding probability on amplified misprimed DNA by means of a computational study on the polymerase chain reaction

    E-Print Network [OSTI]

    Gopalakrishnan, Sanjay

    1999-01-01

    DNA that are formed due to misprimed synthesis, i.e., the DNA that are not of interest, are due to the variation in the probability values of primer binding for increasing cycles in the presence of multiple binding sites. First, background information...

  14. Calculation of positron binding energies using the generalized any particle propagator theory

    SciTech Connect (OSTI)

    Romero, Jonathan; Charry, Jorge A.; Flores-Moreno, Roberto; Varella, Mrcio T. do N.; Reyes, Andrs

    2014-09-21

    We recently extended the electron propagator theory to any type of quantum species based in the framework of the Any-Particle Molecular Orbital (APMO) approach [J. Romero, E. Posada, R. Flores-Moreno, and A. Reyes, J. Chem. Phys. 137, 074105 (2012)]. The generalized any particle molecular orbital propagator theory (APMO/PT) was implemented in its quasiparticle second order version in the LOWDIN code and was applied to calculate nuclear quantum effects in electron binding energies and proton binding energies in molecular systems [M. Daz-Tinoco, J. Romero, J. V. Ortiz, A. Reyes, and R. Flores-Moreno, J. Chem. Phys. 138, 194108 (2013)]. In this work, we present the derivation of third order quasiparticle APMO/PT methods and we apply them to calculate positron binding energies (PBEs) of atoms and molecules. We calculated the PBEs of anions and some diatomic molecules using the second order, third order, and renormalized third order quasiparticle APMO/PT approaches and compared our results with those previously calculated employing configuration interaction (CI), explicitly correlated and quantum Montecarlo methodologies. We found that renormalized APMO/PT methods can achieve accuracies of ?0.35 eV for anionic systems, compared to Full-CI results, and provide a quantitative description of positron binding to anionic and highly polar species. Third order APMO/PT approaches display considerable potential to study positron binding to large molecules because of the fifth power scaling with respect to the number of basis sets. In this regard, we present additional PBE calculations of some small polar organic molecules, amino acids and DNA nucleobases. We complement our numerical assessment with formal and numerical analyses of the treatment of electron-positron correlation within the quasiparticle propagator approach.

  15. High-Affinity and Cooperative Binding of Oxidized Calmodulin by Methionine Sulfoxide Reductase

    SciTech Connect (OSTI)

    Xiong, Yijia; Chen, Baowei; Smallwood, Heather S.; Urbauer, Ramona J.; Markillie, Lye Meng; Galeva, Nadezhda A.; Williams, Todd D.; Squier, Thomas C.

    2006-12-12

    Methionines play an important role in modulating protein-protein interactions associated with intracellular signaling, and their reversible oxidation to form methionine sulfoxides [Met(O)] in calmodulin (CaM) and other signaling proteins has been suggested to couple cellular redox changes to protein function changes through the action of methionine sulfoxide reductases (Msr). Prior measurements indicate the full recovery of target protein activation upon the stereospecific reduction of oxidized CaM by MsrA, where the formation of the S-stereoisomer of Met(O) selectively inhibits the CaM-dependent activation of the Ca-ATPase. However, the physiological substrates of MsrA remain unclear, as neither the binding specificities nor affinities of protein targets have been measured. To assess the specificity of binding and its possible importance in the maintenance of CaM function, we have measured the kinetics of repair and the binding affinity between oxidized CaM and MsrA. Reduction of Met(O) in fully oxidized CaM by MsrA is sensitive to protein folding, as repair of the intact protein is incomplete, with > 6 Met(O) remaining in each CaM following MsrA reduction. In contrast, following proteolytic digestion, MsrA is able to fully reduce one-half of the oxidized methionines, indicating that Met(O) within folded proteins are not substrates for MsrA repair. Further, in comparison to free Met(O), the turnover number and Km for oxidized CaM (CaMox) are substantially smaller, indicating that the binding interaction retards Msr recycling to reduce steady-state enzyme activity. Mutation of the active site (i.e., C72S) in MsrA permitted equilibrium-binding measurements using both ensemble and single-molecule measurements obtained by fluorescence correlation spectroscopy (FCS). Multiple MsrA bind tightly to CaMox (Kd = 70 +- 10 nM) with an affinity that is three orders of magnitude greater than the Michaelis constant (KM = 71 +- 8 micromolar). These results indicate that MsrA selectively reduces surface-exposed Met(O) within unstructured sequences and suggest that only a small subset of oxidized proteins are substrates for MsrA, which may selectively modulate the function of key signaling proteins as part of an adaptive response to oxidative stress.

  16. The structures of non-CG-repeat Z-DNAs co-crystallized with the Z-DNA-binding domain, hZ?ADAR1

    E-Print Network [OSTI]

    Ha, Sung Chul

    The Z-DNA conformation preferentially occurs at alternating purine-pyrimidine repeats, and is specifically recognized by Z? domains identified in several Z-DNA-binding proteins. The binding of Z? to foreign or chromosomal ...

  17. Membrane binding mode of intrinsically disordered cytoplasmic domains of T cell receptor signaling subunits depends on lipid composition

    SciTech Connect (OSTI)

    Sigalov, Alexander B., E-mail: Alexander.sigalov@umassmed.edu [University of Massachusetts Medical School, Worcester, MA 01655 (United States); Hendricks, Gregory M. [University of Massachusetts Medical School, Worcester, MA 01655 (United States)] [University of Massachusetts Medical School, Worcester, MA 01655 (United States)

    2009-11-13

    Intrinsically disordered cytoplasmic domains of T cell receptor (TCR) signaling subunits including {zeta}{sub cyt} and CD3{epsilon}{sub cyt} all contain one or more copies of an immunoreceptor tyrosine-based activation motif (ITAM), tyrosine residues of which are phosphorylated upon receptor triggering. Membrane binding-induced helical folding of {zeta}{sub cyt} and CD3{epsilon}{sub cyt} ITAMs is thought to control TCR activation. However, the question whether or not lipid binding of {zeta}{sub cyt} and CD3{epsilon}{sub cyt} is necessarily accompanied by a folding transition of ITAMs remains open. In this study, we investigate whether the membrane binding mechanisms of {zeta}{sub cyt} and CD3{epsilon}{sub cyt} depend on the membrane model used. Circular dichroic and fluorescence data indicate that binding of {zeta}{sub cyt} and CD3{epsilon}{sub cyt} to detergent micelles and unstable vesicles is accompanied by a disorder-to-order transition, whereas upon binding to stable vesicles these proteins remain unfolded. Using electron microscopy and dynamic light scattering, we show that upon protein binding, unstable vesicles fuse and rupture. In contrast, stable vesicles remain intact under these conditions. This suggests different membrane binding modes for {zeta}{sub cyt} and CD3{epsilon}{sub cyt} depending on the bilayer stability: (1) coupled binding and folding, and (2) binding without folding. These findings explain the long-standing puzzle in the literature and highlight the importance of the choice of an appropriate membrane model for protein-lipid interactions studies.

  18. Structural determinants of nuclear export signal orientation in binding to exportin CRM1

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Fung, Ho Yee Joyce; Fu, Szu -Chin; Brautigam, Chad A.; Chook, Yuh Min

    2015-09-08

    The Chromosome Region of Maintenance 1 (CRM1) protein mediates nuclear export of hundreds of proteins through recognition of their nuclear export signals (NESs), which are highly variable in sequence and structure. The plasticity of the CRM1-NES interaction is not well understood, as there are many NES sequences that seem incompatible with structures of the NES-bound CRM1 groove. Crystal structures of CRM1 bound to two different NESs with unusual sequences showed the NES peptides binding the CRM1 groove in the opposite orientation (minus) to that of previously studied NESs (plus). A comparison of minus and plus NESs identified structural and sequencemoredeterminants for NES orientation. The binding of NESs to CRM1 in both orientations results in a large expansion in NES consensus patterns and therefore a corresponding expansion of potential NESs in the proteome.less

  19. Structural basis of CX-4945 binding to human protein kinase CK2

    SciTech Connect (OSTI)

    Ferguson, Andrew D.; Sheth, Payal R.; Basso, Andrea D.; Paliwal, Sunil; Gray, Kimberly; Fischmann, Thierry O.; Le, Hung V. (Merck)

    2012-02-07

    Protein kinase CK2 (CK2), a constitutively active serine/threonine kinase, is involved in a variety of roles essential to the maintenance of cellular homeostasis. Elevated levels of CK2 expression results in the dysregulation of key signaling pathways that regulate transcription, and has been implicated in cancer. The adenosine-5'-triphosphate-competitive inhibitor CX-4945 has been reported to show broad spectrum anti-proliferative activity in multiple cancer cell lines. Although the enzymatic IC{sub 50} of CX-4945 has been reported, the thermodynamics and structural basis of binding to CK2{alpha} remained elusive. Presented here are the crystal structures of human CK2{alpha} in complex with CX-4945 and adenylyl phosphoramidate at 2.7 and 1.3 {angstrom}, respectively. Biophysical analysis of CX-4945 binding is also described. This data provides the structural rationale for the design of more potent inhibitors against this emerging cancer target.

  20. Capture and release of mixed acid gasses with binding organic liquids

    DOE Patents [OSTI]

    Heldebrant, David J. (Richland, WA); Yonker, Clement R. (Kennewick, WA)

    2010-09-21

    Reversible acid-gas binding organic liquid systems that permit separation and capture of one or more of several acid gases from a mixed gas stream, transport of the liquid, release of the acid gases from the ionic liquid and reuse of the liquid to bind more acid gas with significant energy savings compared to current aqueous systems. These systems utilize acid gas capture compounds made up of strong bases and weak acids that form salts when reacted with a selected acid gas, and which release these gases when a preselected triggering event occurs. The various new materials that make up this system can also be included in various other applications such as chemical sensors, chemical reactants, scrubbers, and separators that allow for the specific and separate removal of desired materials from a gas stream such as flue gas.

  1. Binding energy for hydrogen-like atoms in the Nelson model without cutoffs

    E-Print Network [OSTI]

    Christian Hainzl; Masao Hirokawa; Herbert Spohn

    2003-12-10

    In the Nelson model particles interact through a scalar massless field. For hydrogen-like atoms there is a nucleus of infinite mass and charge $Ze$, $Z > 0$, fixed at the origin and an electron of mass $m$ and charge $e$. This system forms a bound state with binding energy $E_{\\rm bin} = me^4Z^2/2$ to leading order in $e$. We investigate the radiative corrections to the binding energy and prove upper and lower bounds which imply that $ E_{\\rm bin} = me^4 Z^2/2 + c_0 e^6 + \\Ow(e^7 \\ln e)$ with explicit coefficient $c_0$ and independent of the ultraviolet cutoff. $c_0$ can be computed by perturbation theory, which however is only formal since for the Nelson Hamiltonian the smallest eigenvalue sits exactly at the bottom of the continuous spectrum.

  2. Extended Lagrangian Density Functional Tight-Binding Molecular Dynamics for Molecules and Solids

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Aradi, Blint; Niklasson, Anders M. N.; Frauenheim, Thomas

    2015-06-26

    A computationally fast quantum mechanical molecular dynamics scheme using an extended Lagrangian density functional tight-binding formulation has been developed and implemented in the DFTB+ electronic structure program package for simulations of solids and molecular systems. The scheme combines the computational speed of self-consistent density functional tight-binding theory with the efficiency and long-term accuracy of extended Lagrangian BornOppenheimer molecular dynamics. Furthermore, for systems without self-consistent charge instabilities, only a single diagonalization or construction of the single-particle density matrix is required in each time step. The molecular dynamics simulation scheme can also be applied to a broad range of problems in materialsmorescience, chemistry, and biology.less

  3. HDL surface lipids mediate CETP binding as revealed by electron microscopy and molecular dynamics simulation

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Zhang, Meng; Charles, River; Tong, Huimin; Zhang, Lei; Patel, Mili; Wang, Francis; Rames, Matthew J.; Ren, Amy; Rye, Kerry-Anne; Qiu, Xiayang; et al

    2015-03-04

    Cholesteryl ester transfer protein (CETP) mediates the transfer of cholesterol esters (CE) from atheroprotective high-density lipoproteins (HDL) to atherogenic low-density lipoproteins (LDL). CETP inhibition has been regarded as a promising strategy for increasing HDL levels and subsequently reducing the risk of cardiovascular diseases (CVD). Although the crystal structure of CETP is known, little is known regarding how CETP binds to HDL. Here, we investigated how various HDL-like particles interact with CETP by electron microscopy and molecular dynamics simulations. Results showed that CETP binds to HDL via hydrophobic interactions rather than protein-protein interactions. The HDL surface lipid curvature generates a hydrophobicmoreenvironment, leading to CETP hydrophobic distal end interaction. This interaction is independent of other HDL components, such as apolipoproteins, cholesteryl esters and triglycerides. Thus, disrupting these hydrophobic interactions could be a new therapeutic strategy for attenuating the interaction of CETP with HDL.less

  4. Nucleic acids encoding phloem small RNA-binding proteins and transgenic plants comprising them

    DOE Patents [OSTI]

    Lucas, William J.; Yoo, Byung-Chun; Lough, Tony J.; Varkonyi-Gasic, Erika

    2007-03-13

    The present invention provides a polynucleotide sequence encoding a component of the protein machinery involved in small RNA trafficking, Cucurbita maxima phloem small RNA-binding protein (CmPSRB 1), and the corresponding polypeptide sequence. The invention also provides genetic constructs and transgenic plants comprising the polynucleotide sequence encoding a phloem small RNA-binding protein to alter (e.g., prevent, reduce or elevate) non-cell autonomous signaling events in the plants involving small RNA metabolism. These signaling events are involved in a broad spectrum of plant physiological and biochemical processes, including, for example, systemic resistance to pathogens, responses to environmental stresses, e.g., heat, drought, salinity, and systemic gene silencing (e.g., viral infections).

  5. Protein/Ligand Binding Free Energies Calculated with Quantum Mechanics/Molecular Frauke Gra1ter,, Sonja M. Schwarzl,, Annick Dejaegere,| Stefan Fischer,*, and

    E-Print Network [OSTI]

    Grter, Frauke

    Protein/Ligand Binding Free Energies Calculated with Quantum Mechanics/Molecular Mechanics Frauke of the complexes are predicted (the "docking" problem) as well as in how the free energy is calculated from)solvation during the binding process.3 Typically, binding free energies calculated with these methods have average

  6. Molecular Basis for the High Affinity Binding and Stabilization of Firefly Luciferase by PTC124

    E-Print Network [OSTI]

    Auld, Douglas S.; Lovell, Scott; Thorne, Natasha; Lea, Wendy A.; Maloney, David J.; Shen, Min; Rai, Ganesha; Battaile, Kevin P.; Thomas, Craig J.; Simeonov, Anton; Hanzlik, Robert P.; Inglese, James

    2010-03-16

    Douglas S. Auld, Scott Lovell, Natasha Thorne, Wendy A. Lea, David J. Maloney, Min Shen, Ganesha Rai, Kevin Battaile, Craig J. Thomas, Anton Simeonov, Robert P. Hanzlik, and James Inglese, "Molecular Basis for the High Affinity Binding... contains the authors accepted manuscript. For the publishers version, see the link in the header of this document.] Paper citation: Douglas S. Auld, Scott Lovell, Natasha Thorne, Wendy A. Lea, David J. Maloney, Min Shen, Ganesha Rai, Kevin...

  7. Substrate masking: binding of RNA by EGTA-inactivated micrococcal nuclease results in artifactual inhibition of RNA processing reactions

    E-Print Network [OSTI]

    Wang, Ming Jing; Gegenheimer, Peter Albert

    1991-01-01

    -directed mutagenesis ofMN (2) has recently allowed separate identification of residues involved in metal binding, in nucleic acid binding, or in catalysis. These studies together led to a catalytic mechanism which involves nucleophilic attack on phosphorus by a water... of the same data; the solid line is a plot of Eqn. II (Materials and Methods) using the constants derived above. reduction of nitrocellulose filter-bound pre-tRNA. From the IC50 values (concentration giving 50% inhibition of binding) of these compounds, we can...

  8. Subfamily-specific adaptations in the structures of two penicillin-binding proteins from Mycobacterium tuberculosis

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Prigozhin, Daniil M.; Krieger, Inna V.; Huizar, John P.; Mavrici, Daniela; Waldo, Geoffrey S.; Hung, Li -Wei; Sacchettini, James C.; Terwilliger, Thomas C.; Alber, Tom; Mayer, Claudine

    2014-12-31

    Beta-lactam antibiotics target penicillin-binding proteins including several enzyme classes essential for bacterial cell-wall homeostasis. To better understand the functional and inhibitor-binding specificities of penicillin-binding proteins from the pathogen, Mycobacterium tuberculosis, we carried out structural and phylogenetic analysis of two predicted D,D-carboxypeptidases, Rv2911 and Rv3330. Optimization of Rv2911 for crystallization using directed evolution and the GFP folding reporter method yielded a soluble quadruple mutant. Structures of optimized Rv2911 bound to phenylmethylsulfonyl fluoride and Rv3330 bound to meropenem show that, in contrast to the nonspecific inhibitor, meropenem forms an extended interaction with the enzyme along a conserved surface. Phylogenetic analysis shows thatmoreRv2911 and Rv3330 belong to different clades that emerged in Actinobacteria and are not represented in model organisms such as Escherichia coli and Bacillus subtilis. Clade-specific adaptations allow these enzymes to fulfill distinct physiological roles despite strict conservation of core catalytic residues. The characteristic differences include potential protein-protein interaction surfaces and specificity-determining residues surrounding the catalytic site. Overall, these structural insights lay the groundwork to develop improved beta-lactam therapeutics for tuberculosis.less

  9. Protein arginine deiminase 2 binds calcium in an ordered fashion: Implications for inhibitor design

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Slade, Daniel J.; Fang, Pengfei; Dreyton, Christina J.; Zhang, Ying; Fuhrmann, Jakob; Rempel, Don; Bax, Benjamin D.; Coonrod, Scott A.; Lewis, Huw D.; Guo, Min; et al

    2015-01-26

    Protein arginine deiminases (PADs) are calcium-dependent histone-modifying enzymes whose activity is dysregulated in inflammatory diseases and cancer. PAD2 functions as an Estrogen Receptor (ER) coactivator in breast cancer cells via the citrullination of histone tail arginine residues at ER binding sites. Although an attractive therapeutic target, the mechanisms that regulate PAD2 activity are largely unknown, especially the detailed role of how calcium facilitates enzyme activation. To gain insights into these regulatory processes, we determined the first structures of PAD2 (27 in total), and through calcium-titrations by X-ray crystallography, determined the order of binding and affinity for the six calcium ionsmorethat bind and activate this enzyme. These structures also identified several PAD2 regulatory elements, including a calcium switch that controls proper positioning of the catalytic cysteine residue, and a novel active site shielding mechanism. Additional biochemical and mass-spectrometry-based hydrogen/deuterium exchange studies support these structural findings. The identification of multiple intermediate calcium-bound structures along the PAD2 activation pathway provides critical insights that will aid the development of allosteric inhibitors targeting the PADs.less

  10. Assessment of Density Functional Methods for Exciton Binding Energies and Related Optoelectronic Properties

    E-Print Network [OSTI]

    Lee, Jui-Che; Lin, Shiang-Tai

    2015-01-01

    The exciton binding energy, the energy required to dissociate an excited electron-hole pair into free charge carriers, is one of the key factors to the optoelectronic performance of organic materials. However, it remains unclear whether modern quantum-mechanical calculations, mostly based on Kohn-Sham density functional theory (KS-DFT) and time-dependent density functional theory (TDDFT), are reliably accurate for exciton binding energies. In this study, the exciton binding energies and related optoelectronic properties (e.g., the ionization potentials, electron affinities, fundamental gaps, and optical gaps) of 121 small- to medium-sized molecules are calculated using KS-DFT and TDDFT with various density functionals. Our KS-DFT and TDDFT results are compared with those calculated using highly accurate CCSD and EOM-CCSD methods, respectively. The omegaB97, omegaB97X, and omegaB97X-D functionals are shown to generally outperform (with a mean absolute error of 0.36 eV) other functionals for the properties inve...

  11. Assessment of Density Functional Methods for Exciton Binding Energies and Related Optoelectronic Properties

    E-Print Network [OSTI]

    Jui-Che Lee; Jeng-Da Chai; Shiang-Tai Lin

    2015-08-29

    The exciton binding energy, the energy required to dissociate an excited electron-hole pair into free charge carriers, is one of the key factors to the optoelectronic performance of organic materials. However, it remains unclear whether modern quantum-mechanical calculations, mostly based on Kohn-Sham density functional theory (KS-DFT) and time-dependent density functional theory (TDDFT), are reliably accurate for exciton binding energies. In this study, the exciton binding energies and related optoelectronic properties (e.g., the ionization potentials, electron affinities, fundamental gaps, and optical gaps) of 121 small- to medium-sized molecules are calculated using KS-DFT and TDDFT with various density functionals. Our KS-DFT and TDDFT results are compared with those calculated using highly accurate CCSD and EOM-CCSD methods, respectively. The omegaB97, omegaB97X, and omegaB97X-D functionals are shown to generally outperform (with a mean absolute error of 0.36 eV) other functionals for the properties investigated.

  12. A novel cofactor-binding mode in bacterial IMP dehydrogenases explains inhibitor selectivity

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Makowska-Grzyska, Magdalena; Kim, Youngchang; Maltseva, Natalia; Osipiuk, Jerzy; Gu, Minyi; Zhang, Minjia; Mandapati, Kavitha; Gollapalli, Deviprasad R.; Gorla, Suresh Kumar; Hedstrom, Lizbeth; et al

    2015-01-09

    The steadily rising frequency of emerging diseases and antibiotic resistance creates an urgent need for new drugs and targets. Inosine 5'-monophosphate dehydrogenase (IMP dehydrogenase or IMPDH) is a promising target for the development of new antimicrobial agents. IMPDH catalyzes the oxidation of IMP to XMP with the concomitant reduction of NAD+, which is the pivotal step in the biosynthesis of guanine nucleotides. Potent inhibitors of bacterial IMPDHs have been identified that bind in a structurally distinct pocket that is absent in eukaryotic IMPDHs. The physiological role of this pocket was not understood. Here, we report the structures of complexes withmoredifferent classes of inhibitors of Bacillus anthracis, Campylobacter jejuni, and Clostridium perfringens IMPDHs. These structures in combination with inhibition studies provide important insights into the interactions that modulate selectivity and potency. We also present two structures of the Vibrio cholerae IMPDH in complex with IMP/NAD+ and XMP/NAD+. In both structures, the cofactor assumes a dramatically different conformation than reported previously for eukaryotic IMPDHs and other dehydrogenases, with the major change observed for the position of the NAD+ adenosine moiety. More importantly, this new NAD+-binding site involves the same pocket that is utilized by the inhibitors. Thus, the bacterial IMPDH-specific NAD+-binding mode helps to rationalize the conformation adopted by several classes of prokaryotic IMPDH inhibitors. As a result, these findings offer a potential strategy for further ligand optimization.less

  13. Enhancing DNA binding rate using optical trapping of high-density gold nanodisks

    SciTech Connect (OSTI)

    Lin, En-Hung; Pan, Ming-Yang [Institute of Photonics Technologies, National Tsing Hua University, Hsinchu, Taiwan 30013 (China) [Institute of Photonics Technologies, National Tsing Hua University, Hsinchu, Taiwan 30013 (China); Research Center for Applied Sciences, Academia Sinica, Taipei, Taiwan 11529 (China); Lee, Ming-Chang [Institute of Photonics Technologies, National Tsing Hua University, Hsinchu, Taiwan 30013 (China)] [Institute of Photonics Technologies, National Tsing Hua University, Hsinchu, Taiwan 30013 (China); Wei, Pei-Kuen, E-mail: pkwei@sinica.edu.tw [Research Center for Applied Sciences, Academia Sinica, Taipei, Taiwan 11529 (China) [Research Center for Applied Sciences, Academia Sinica, Taipei, Taiwan 11529 (China); Institute of Biophotonics, National Yang-Ming University, Taipei 11221, Taiwan (China)

    2014-03-15

    We present the dynamic study of optical trapping of fluorescent molecules using high-density gold nanodisk arrays. The gold nanodisks were fabricated by electron beam lithography with a diameter of 500 nm and a period of 1 ?m. Dark-field illumination showed ?15 times enhancement of fluorescence near edges of nanodisks. Such enhanced near-field generated an optical trapping force of ?10 fN under 3.58 10{sup 3} W/m{sup 2} illumination intensity as calculated from the Brownian motions of 590 nm polystyrene beads. Kinetic observation of thiolated DNA modified with Cy5 dye showed different binding rates of DNA under different illumination intensity. The binding rate increased from 2.14 10{sup 3} s{sup ?1} (I = 0.7 10{sup 3} W/m{sup 2}) to 1.15 10{sup 5} s{sup ?1} (I = 3.58 10{sup 3} W/m{sup 2}). Both enhanced fluorescence and binding rate indicate that gold nanodisks efficiently improve both detection limit and interaction time for microarrays.

  14. The N-terminus of TDP-43 promotes its oligomerization and enhances DNA binding affinity

    SciTech Connect (OSTI)

    Chang, Chung-ke [Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan (China)] [Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan (China); Wu, Tzong-Huah [Institute of Chemistry, Academia Sinica, Taipei 115, Taiwan (China) [Institute of Chemistry, Academia Sinica, Taipei 115, Taiwan (China); Chemical Biology and Molecular Biophysics Program, Taiwan International Graduate Program, Institute of Biochemistry, Academia Sinica, Taipei 115, Taiwan (China); Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu 300, Taiwan (China); Wu, Chu-Ya [Institute of Chemistry, Academia Sinica, Taipei 115, Taiwan (China) [Institute of Chemistry, Academia Sinica, Taipei 115, Taiwan (China); Graduate Institute of Engineering, National Taiwan University of Science and Technology, Taipei 106, Taiwan (China); Chiang, Ming-hui; Toh, Elsie Khai-Woon [Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan (China)] [Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan (China); Hsu, Yin-Chih; Lin, Ku-Feng [Institute of Chemistry, Academia Sinica, Taipei 115, Taiwan (China)] [Institute of Chemistry, Academia Sinica, Taipei 115, Taiwan (China); Liao, Yu-heng [Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan (China)] [Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan (China); Huang, Tai-huang, E-mail: bmthh@gate.sinica.edu.tw [Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan (China) [Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan (China); Department of Physics, National Taiwan Normal University, Taipei 106, Taiwan (China); Huang, Joseph Jen-Tse, E-mail: jthuang@chem.sinica.edu.tw [Institute of Chemistry, Academia Sinica, Taipei 115, Taiwan (China)

    2012-08-24

    Highlights: Black-Right-Pointing-Pointer The N-terminus of TDP-43 contains an independently folded structural domain (NTD). Black-Right-Pointing-Pointer The structural domains of TDP-43 are arranged in a beads-on-a-string fashion. Black-Right-Pointing-Pointer The NTD promotes TDP-43 oligomerization in a concentration-dependent manner. Black-Right-Pointing-Pointer The NTD may assist nucleic acid-binding activity of TDP-43. -- Abstract: TDP-43 is a DNA/RNA-binding protein associated with different neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD-U). Here, the structural and physical properties of the N-terminus on TDP-43 have been carefully characterized through a combination of nuclear magnetic resonance (NMR), circular dichroism (CD) and fluorescence anisotropy studies. We demonstrate for the first time the importance of the N-terminus in promoting TDP-43 oligomerization and enhancing its DNA-binding affinity. An unidentified structural domain in the N-terminus is also disclosed. Our findings provide insights into the N-terminal domain function of TDP-43.

  15. Identification of FAM96B as a novel prelamin A binding partner

    SciTech Connect (OSTI)

    Xiong, Xing-Dong; Wang, Junwen; Zheng, Huiling; Jing, Xia; Liu, Zhenjie; Institute of Biochemistry and Molecular Biology, Guangdong Medical College, Zhanjiang 524023; Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Dongguan 523808 ; Zhou, Zhongjun; Department of Biochemistry, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong ; Liu, Xinguang; Institute of Biochemistry and Molecular Biology, Guangdong Medical College, Zhanjiang 524023; Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Dongguan 523808

    2013-10-11

    Highlights: We screen the binding protein of prelamin A by yeast two-hybrid screen. FAM96B colocalizes with prelamin A in HEK-293 cells. FAM96B physically interacts with prelamin A. -- Abstract: Prelamin A accumulation causes nuclear abnormalities, impairs nuclear functions, and eventually promotes cellular senescence. However, the underlying mechanism of how prelamin A promotes cellular senescence is still poorly understood. Here we carried out a yeast two-hybrid screen using a human skeletal muscle cDNA library to search for prelamin A binding partners, and identified FAM96B as a prelamin A binding partner. The interaction of FAM96B with prelamin A was confirmed by GST pull-down and co-immunoprecipitation experiments. Furthermore, co-localization experiments by fluorescent confocal microscopy revealed that FAM96B colocalized with prelamin A in HEK-293 cells. Taken together, our data demonstrated the physical interaction between FAM96B and prelamin A, which may provide some clues to the mechanisms of prelamin A in premature aging.

  16. A Novel, ;Double-Clamp; Binding Mode for Human Heme Oxygenase-1 Inhibition

    SciTech Connect (OSTI)

    Rahman, Mona N.; Vlahakis, Jason Z.; Vukomanovic, Dragic; Lee, Wallace; Szarek, Walter A.; Nakatsu, Kanji; Jia, Zongchao

    2012-08-01

    The development of heme oxygenase (HO) inhibitors is critical in dissecting and understanding the HO system and for potential therapeutic applications. We have established a program to design and optimize HO inhibitors using structure-activity relationships in conjunction with X-ray crystallographic analyses. One of our previous complex crystal structures revealed a putative secondary hydrophobic binding pocket which could be exploited for a new design strategy by introducing a functional group that would fit into this potential site. To test this hypothesis and gain further insights into the structural basis of inhibitor binding, we have synthesized and characterized 1-(1H-imidazol-1-yl)-4,4-diphenyl-2-butanone (QC-308). Using a carbon monoxide (CO) formation assay on rat spleen microsomes, the compound was found to be {approx}15 times more potent (IC{sub 50} = 0.27{+-}0.07 {mu}M) than its monophenyl analogue, which is already a potent compound in its own right (QC-65; IC{sub 50} = 4.0{+-}1.8 {mu}M). The crystal structure of hHO-1 with QC-308 revealed that the second phenyl group in the western region of the compound is indeed accommodated by a definitive secondary proximal hydrophobic pocket. Thus, the two phenyl moieties are each stabilized by distinct hydrophobic pockets. This 'double-clamp' binding offers additional inhibitor stabilization and provides a new route for improvement of human heme oxygenase inhibitors.

  17. Structural and Energetic Analysis of Activiation by a Cyclic Nucleotide Binding Domain

    SciTech Connect (OSTI)

    Altieri,S.; Clayton, G.; Silverman, W.; Olivares, A.; De La Cruz, E.; Thomas, L.; Morais-Cabral, J.

    2008-01-01

    MlotiK1 is a prokaryotic homolog of cyclic-nucleotide-dependent ion channels that contains an intracellular C-terminal cyclic nucleotide binding (CNB) domain. X-ray structures of the CNB domain have been solved in the absence of ligand and bound to cAMP. Both the full-length channel and CNB domain fragment are easily expressed and purified, making MlotiK1 a useful model system for dissecting activation by ligand binding. We have used X-ray crystallography to determine three new MlotiK1 CNB domain structures: a second apo configuration, a cGMP-bound structure, and a second cAMP-bound structure. In combination, the five MlotiK1 CNB domain structures provide a unique opportunity for analyzing, within a single protein, the structural differences between the apo state and the bound state, and the structural variability within each state. With this analysis as a guide, we have probed the nucleotide selectivity and importance of specific residue side chains in ligand binding and channel activation. These data help to identify ligand-protein interactions that are important for ligand dependence in MlotiK1 and, more globally, in the class of nucleotide-dependent proteins.

  18. Structural insights into the mechanisms of membrane binding and oligomerization of a bacterial pore-forming toxin

    E-Print Network [OSTI]

    Ramachandran, Rajesh

    2006-04-12

    Perfringolysin O (PFO), a cytolytic toxin from by the pathogenic bacterium Clostridium perfringens, perforates mammalian cell membranes by forming large aqueous pores. Secreted as water-soluble monomers, the toxin molecules bind to cholesterol...

  19. Anais do IHC 2006 19-22 de Novembro, Natal, RN, Brasil Extreme Designing: Binding Sketching to an Interaction

    E-Print Network [OSTI]

    Barbosa, Simone Diniz Junqueira

    Anais do IHC 2006 19-22 de Novembro, Natal, RN, Brasil 101 Extreme Designing: Binding Sketching Vicente, 225 Gvea, Rio de Janeiro, RJ, Brasil, 22451-900 +55 21 3527-1500 ext. 4353 {brunosantana

  20. Quantitative Estimates on the Binding Energy for Hydrogen in Non-Relativistic QED. II. The spin case

    E-Print Network [OSTI]

    Jean-Marie Barbaroux; Semjon Vugalter

    2013-06-19

    The hydrogen binding energy in the Pauli-Fierz model with the spin Zeeman term is determined up to the order alpha cube, where alpha denotes the fine-structure constant.

  1. Searching for the nik Operon: How a Ligand-Responsive Transcription Factor Hunts for Its DNA Binding Site

    E-Print Network [OSTI]

    Phillips, Christine M.

    Transcription factors regulate a wide variety of genes in the cell and play a crucial role in maintaining cellular homeostasis. A major unresolved issue is how transcription factors find their specific DNA binding sequence ...

  2. The HSV-1 ICP27 RGG box specifically binds flexible, GC-rich sequences but not G-quartet structures

    E-Print Network [OSTI]

    Corbin-Lickfett, Kara A.; Chen, I-Hsiung Brandon; Cocco, Melanie J.; Sandri-Goldin, Rozanne M.

    2009-01-01

    recognition complex (ORC) proteins to the EBV episomal mini-the binding by EBNA1 to the ORC proteins was RNA dependentrich RNA may be a mechanism for ORC recruitment (41). It is

  3. Curated collection of yeast transcription factor DNA binding specificity data reveals novel structural and gene regulatory insights

    E-Print Network [OSTI]

    Gordan, Raluca

    Background: Transcription factors (TFs) play a central role in regulating gene expression by interacting with cis-regulatory DNA elements associated with their target genes. Recent surveys have examined the DNA binding ...

  4. Novel stochastic and entropy-based Expectation-Maximisation algorithm for transcription factor binding site motif discovery

    E-Print Network [OSTI]

    Kilpatrick, Alastair Morris

    2015-06-29

    The discovery of transcription factor binding site (TFBS) motifs remains an important and challenging problem in computational biology. This thesis presents MITSU, a novel algorithm for TFBS motif discovery which exploits ...

  5. Understanding Weak Binding for Phospho(enol)pyruvate to the Allosteric Site of Phosphofructokinase from Lactobacillus delbrueckii subspecies bulgaricus

    E-Print Network [OSTI]

    Ferguson, Scarlett Blair

    2012-10-19

    Phosphofructokinase (PFK) from the lactic acid bacterium Lactobacillus delbrueckii subspecies bulgaricus (LbPFK) is a non-allosteric PFK with weak binding affinity for both the allosteric ligands phospho(enol)pyruvate (PEP) ...

  6. JAB1 regulates unphosphorylated STAT3 DNA-binding activity through proteinprotein interaction in human colon cancer cells

    SciTech Connect (OSTI)

    Nishimoto, Arata, E-mail: anishimo@yamaguchi-u.ac.jp [Department of Surgery and Clinical Science, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi 755-8505 (Japan)] [Department of Surgery and Clinical Science, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi 755-8505 (Japan); Kugimiya, Naruji; Hosoyama, Toru; Enoki, Tadahiko [Department of Surgery and Clinical Science, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi 755-8505 (Japan)] [Department of Surgery and Clinical Science, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi 755-8505 (Japan); Li, Tao-Sheng [Department of Stem Cell Biology, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki 852-8523 (Japan)] [Department of Stem Cell Biology, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki 852-8523 (Japan); Hamano, Kimikazu [Department of Surgery and Clinical Science, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi 755-8505 (Japan)] [Department of Surgery and Clinical Science, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi 755-8505 (Japan)

    2013-08-30

    Highlights: JAB1 interacted with unphosphorylated STAT3 in the nucleus. JAB1 knockdown tended to increase nuclear STAT3 expression. JAB1 knockdown significantly decreased unphosphorylated STAT3 DNA-binding activity. JAB1 knockdown significantly decreased MDR1, NANOG, and VEGF expressions. Nuclear JAB1, but not nuclear STAT3, correlated with STAT3 DNA-binding activity. -- Abstract: Recent studies have revealed that unphosphorylated STAT3 forms a dimer, translocates to the nucleus, binds to the STAT3 binding site, and activates the transcription of STAT3 target genes, thereby playing an important role in oncogenesis in addition to phosphorylated STAT3. Among signaling steps of unphosphorylated STAT3, nuclear translocation and target DNA-binding are the critical steps for its activation. Therefore, elucidating the regulatory mechanism of these signaling steps of unphosphorylated STAT3 is a potential step in the discovery of a novel cancer drug. However, the mechanism of unphosphorylated STAT3 binding to the promoter of target genes remains unclear. In this study, we focused on Jun activation domain-binding protein 1 (JAB1) as a candidate protein that regulates unphosphorylated STAT3 DNA-binding activity. Initially, we observed that both unphosphorylated STAT3 and JAB1 existed in the nucleus of human colon cancer cell line COLO205 at the basal state (no cytokine stimulation). On the other hand, phosphorylated STAT3 did not exist in the nucleus of COLO205 cells at the basal state. Immunoprecipitation using nuclear extract of COLO205 cells revealed that JAB1 interacted with unphosphorylated STAT3. To investigate the effect of JAB1 on unphosphorylated STAT3 activity, RNAi studies were performed. Although JAB1 knockdown tended to increase nuclear STAT3 expression, it significantly decreased unphosphorylated STAT3 DNA-binding activity. Subsequently, JAB1 knockdown significantly decreased the expression levels of MDR1, NANOG, and VEGF, which are STAT3 target genes. Furthermore, the expression level of nuclear JAB1, but not nuclear STAT3, correlated with unphosphorylated STAT3 DNA-binding activity between COLO205 and LoVo cells. Taken together, these results suggest that nuclear JAB1 positively regulates unphosphorylated STAT3 DNA-binding activity through proteinprotein interaction in human colon cancer cell line COLO205.

  7. Binding of soluble immune complexes to adult Schistosoma mansoni: evidence for IgG-Fc and complement receptors

    E-Print Network [OSTI]

    Tarleton, Ricky Lee

    1980-01-01

    BINDING OF SOLUBLE IMMUNE COMPLEXES TO ADULT SCHISTOSOMA MANSONI: EVIDENCE FOR IgG-Fc AND COMPLEMENT RECEPTORS A Thesis RICKY LEE TARLETDN Submitted to the Graduate College of Texas A&M University in partial fulfillment of the requirement... for the degree of MASTER OF'SCIENCE May 1980 Major Subject: Microbiology BINDING OF SOLUBLE INMUNE COMPLEXES TO ADULT SCHISTOSOMA MANSONI: EVIDENCE FOR IgG-Fc AND COMPLEMENT RECEPTORS A Thesis RICKY LEE TARLETON Approved as to style and content by...

  8. The effect of heat stress on 1,25-dihydroxycholecalciferol induced calcium-binding protein in laying hens

    E-Print Network [OSTI]

    Schaeffer, Bonnie Harriet Kay

    1988-01-01

    THE EFFECT OF HEAT STRESS ON 1, 25-DIHYDROXYCHOLECALCIFEROL INDUCED CALCIUM-BINDING PROTEIN IN LAYING HENS A Thesis by BONNIE HARRIET KAY SCHAEFFER Submitted to the Office of Graduate Studies Texas AErM University in partial fulfillment... of the requirements for the degree of MASTER OF SCIENCE August 1988 Major Subject: Nutrition THE EFFECT OF HEAT STRESS ON 1, 25-DIHYDROXYCBOLECALCIFEROL INDUCED CALCIUM-BINDING PROTEIN IN LAYING HENS A Thesis BONNIE HARRIET KAY SCHAEFFER Approved as to style...

  9. Particle trap to sheath non-binding contact for a gas-insulated transmission line having a corrugated outer conductor

    DOE Patents [OSTI]

    Fischer, William H. (Pittsburgh, PA)

    1984-04-24

    A non-binding particle trap to outer sheath contact for use in gas insulated transmission lines having a corrugated outer conductor. The non-binding feature of the contact according to the teachings of the invention is accomplished by having a lever arm rotatably attached to a particle trap by a pivot support axis disposed parallel to the direction of travel of the inner conductor/insulator/particle trap assembly.

  10. Conformational Melding Permits a Conserved Binding Geometry in TCR Recognition of Foreign and Self Molecular Mimics

    SciTech Connect (OSTI)

    Borbulevych, Oleg Y.; Piepenbrink, Kurt H.; Baker, Brian M.

    2012-03-16

    Molecular mimicry between foreign and self Ags is a mechanism of TCR cross-reactivity and is thought to contribute to the development of autoimmunity. The {alpha}{beta} TCR A6 recognizes the foreign Ag Tax from the human T cell leukemia virus-1 when presented by the class I MHC HLA-A2. In a possible link with the autoimmune disease human T cell leukemia virus-1-associated myelopathy/tropical spastic paraparesis, A6 also recognizes a self peptide from the neuronal protein HuD in the context of HLA-A2. We found in our study that the complexes of the HuD and Tax epitopes with HLA-A2 are close but imperfect structural mimics and that in contrast with other recent structures of TCRs with self Ags, A6 engages the HuD Ag with the same traditional binding mode used to engage Tax. Although peptide and MHC conformational changes are needed for recognition of HuD but not Tax and the difference of a single hydroxyl triggers an altered TCR loop conformation, TCR affinity toward HuD is still within the range believed to result in negative selection. Probing further, we found that the HuD-HLA-A2 complex is only weakly stable. Overall, these findings help clarify how molecular mimicry can drive self/nonself cross-reactivity and illustrate how low peptide-MHC stability can permit the survival of T cells expressing self-reactive TCRs that nonetheless bind with a traditional binding mode.

  11. ECRbase: Database of Evolutionary Conserved Regions, Promoters, and Transcription Factor Binding Sites in Vertebrate Genomes

    DOE Data Explorer [Office of Scientific and Technical Information (OSTI)]

    Loots, Gabriela G. [LLNL; Ovcharenko, I. [LLNL

    Evolutionary conservation of DNA sequences provides a tool for the identification of functional elements in genomes. This database of evolutionary conserved regions (ECRs) in vertebrate genomes features a database of syntenic blocks that recapitulate the evolution of rearrangements in vertebrates and a comprehensive collection of promoters in all vertebrate genomes generated using multiple sources of gene annotation. The database also contains a collection of annotated transcription factor binding sites (TFBSs) in evolutionary conserved and promoter elements. ECRbase currently includes human, rhesus macaque, dog, opossum, rat, mouse, chicken, frog, zebrafish, and fugu genomes. (taken from paper in Journal: Bioinformatics, November 7, 2006, pp. 122-124

  12. Four-Quark Binding Energies from SU(2) Lattice Monte Carlo

    E-Print Network [OSTI]

    A. M. Green; C. Michael; M. E. Sainio

    1994-04-11

    Energies of four-quark systems have been extracted in a static quenched SU(2) lattice Monte Carlo calculation for six different geometries, both planar and non-planar, with $\\beta=2.4$ and lattice size $16^3\\times 32$. In all cases, it is found that the binding energy is greatly enhanced when the four quarks can be partitioned in two ways with comparable energies. Also it is shown that the energies of the four-quark states cannot be understood simply in terms of two-quark potentials.

  13. Fluorinated Calixpyrroles: Anion-Binding Extractants that Reduce the Hofmeister Bias

    SciTech Connect (OSTI)

    Levitskaia, Tatiana G.; Marquez, Manuel; Sessler, Jonathan L.; Shriver, James A.; Vercouter, Thomas; Moyer, Bruce A.

    2003-04-30

    b-Fluorinated calix[4]pyrrole 1 and calix[5]pyrrole 2, strong, neutral anion-binding agents, were found to transport small anions effectively while overcoming the classical solvation-based Hofmeister anion bias selectivity. These two receptors showed an ability to extract smaller anions (bromide and chloride for 1 and nitrate and fluoride for 2) as effectively as iodide anion into nitrobenzene (NB). The present results also represent a rare example of liquid-liquid extraction of inorganic salts effected using an anion receptor in the absence of a cation co-extractant.

  14. Determination of the Exciton Binding Energy in CdSe Quantum Dots

    SciTech Connect (OSTI)

    Meulenberg, R; Lee, J; Wolcott, A; Zhang, J; Terminello, L; van Buuren, T

    2009-10-27

    The exciton binding energy (EBE) in CdSe quantum dots (QDs) has been determined using x-ray spectroscopy. Using x-ray absorption and photoemission spectroscopy, the conduction band (CB) and valence band (VB) edge shifts as a function of particle size have been determined and combined to obtain the true band gap of the QDs (i.e. without and exciton). These values can be compared to the excitonic gap obtained using optical spectroscopy to determine the EBE. The experimental EBE results are compared with theoretical calculations on the EBE and show excellent agreement.

  15. Structural Insights into the Cooperative Binding of SeqA to a Tandem GATC Repeat

    SciTech Connect (OSTI)

    Chung, Y.; Brendler, T; Austin, S; Guarne, A

    2009-01-01

    SeqA is a negative regulator of DNA replication in Escherichia coli and related bacteria that functions by sequestering the origin of replication and facilitating its resetting after every initiation event. Inactivation of the seqA gene leads to unsynchronized rounds of replication, abnormal localization of nucleoids and increased negative superhelicity. Excess SeqA also disrupts replication synchrony and affects cell division. SeqA exerts its functions by binding clusters of transiently hemimethylated GATC sequences generated during replication. However, the molecular mechanisms that trigger formation and disassembly of such complex are unclear. We present here the crystal structure of a dimeric mutant of SeqA [SeqA{Delta}(41-59)-A25R] bound to tandem hemimethylated GATC sites. The structure delineates how SeqA forms a high-affinity complex with DNA and it suggests why SeqA only recognizes GATC sites at certain spacings. The SeqA-DNA complex also unveils additional protein-protein interaction surfaces that mediate the formation of higher ordered complexes upon binding to newly replicated DNA. Based on this data, we propose a model describing how SeqA interacts with newly replicated DNA within the origin of replication and at the replication forks.

  16. A New Scaffold of an Old Protein Fold Ensures Binding to the Bisintercalator Thiocoraline

    SciTech Connect (OSTI)

    Biswas, Tapan; Zolova, Olga E.; Lomb, Felipe; de la Calle, Fernando; Salas, Jose A.; Tsodikov, Oleg V.; Garneau-Tsodikova, Sylvie (Michigan); (Oviedo); (PharmaMar)

    2010-09-02

    Thiocoraline is a thiodepsipeptide with potent antitumor activity. TioX, a protein with an unidentified function, is encoded by a gene of the thiocoraline biosynthetic gene cluster. The crystal structure of the full-length TioX protein at 2.15 {angstrom} resolution reveals that TioX protomer shares an ancient {beta}{alpha}{beta}{beta}{beta} fold motif with glyoxalase I and bleomycin resistance protein families, despite a very low sequence homology. Intriguingly, four TioX monomers form a unique 2-fold symmetric tetrameric assembly that is stabilized by four intermolecular disulfide bonds formed cyclically between Cys60 and Cys66 of adjacent monomers. The arrangement of two of the four monomers in the TioX tetramer is analogous to that in dimeric bleomycin resistance proteins. This analogy indicates that this novel higher-order structural scaffold of TioX may have evolved to bind thiocoraline. Our equilibrium titration studies demonstrate the binding of a thiocoraline chromophore analog, quinaldic acid, to TioX, thereby substantiating this model. Furthermore, a strain of Streptomyces albus containing an exogenous thiocoraline gene cluster devoid of functional tioX maintains thiocoraline production, albeit with a lower yield. Taken together, these observations rule out a direct enzymatic function of TioX and suggest that TioX is involved in thiocoraline resistance or secretion.

  17. Tight binding prediction of the {alpha}-Gd{sub 2}S{sub 3} magnetic structure

    SciTech Connect (OSTI)

    Roy, Lindsay E.; Hughbanks, Timothy

    2007-03-15

    Spin-dependent extended Hueckel tight binding (EHTB) calculations were carried out for the magnetic solid Gd{sub 2}S{sub 3} by considering 20 different variations in the ordering of the 4f {sup 7} moments. The tight-binding calculations are used to interpolate the band structure of a nonmagnetic congener (Y{sub 2}S{sub 3}) and the 4f/5d,6s exchange interactions are introduced as perturbations via the introduction of spin-dependent H{sub dd} and H{sub ss} parameters. The calculations predict that Gd{sub 2}S{sub 3} adopts an antiferromagnetic ordering of the 4f {sup 7} moments that is consistent with published neutron diffraction results. Our attempt to account for the calculated energies of the spin patterns using an Ising model was unsuccessful. - Graphical abstract: The spin-dependent EHTB method correctly predicts the magnetic structure of {alpha}-Gd{sub 2}S{sub 3} determined from neutron diffraction experiments.

  18. Insights into the binding of PARP inhibitors to the catalytic domain of human tankyrase-2

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Qiu, Wei; Lam, Robert; Voytyuk, Oleksandr; Romanov, Vladimir; Gordon, Roni; Gebremeskel, Simon; Vodsedalek, Jakub; Thompson, Christine; Beletskaya, Irina; Battaile, Kevin P.; et al

    2014-07-31

    The poly(ADP-ribose) polymerase (PARP) family represents a new class of therapeutic targets with diverse potential disease indications. PARP1 and PARP2 inhibitors have been developed for breast and ovarian tumors manifesting double-stranded DNA-repair defects, whereas tankyrase 1 and 2 (TNKS1 and TNKS2, also known as PARP5a and PARP5b, respectively) inhibitors have been developed for tumors with elevated ?-catenin activity. As the clinical relevance of PARP inhibitors continues to be actively explored, there is heightened interest in the design of selective inhibitors based on the detailed structural features of how small-molecule inhibitors bind to each of the PARP family members. Here, themorehigh-resolution crystal structures of the human TNKS2 PARP domain in complex with 16 various PARP inhibitors are reported, including the compounds BSI-201, AZD-2281 and ABT-888, which are currently in Phase 2 or 3 clinical trials. These structures provide insight into the inhibitor-binding modes for the tankyrase PARP domain and valuable information to guide the rational design of future tankyrase-specific inhibitors.less

  19. Insights into the binding of PARP inhibitors to the catalytic domain of human tankyrase-2

    SciTech Connect (OSTI)

    Qiu, Wei; Lam, Robert; Voytyuk, Oleksandr; Romanov, Vladimir; Gordon, Roni; Gebremeskel, Simon; Vodsedalek, Jakub; Thompson, Christine; Beletskaya, Irina; Battaile, Kevin P.; Pai, Emil F.; Rottapel, Robert; Chirgadze, Nickolay Y.

    2014-07-31

    The poly(ADP-ribose) polymerase (PARP) family represents a new class of therapeutic targets with diverse potential disease indications. PARP1 and PARP2 inhibitors have been developed for breast and ovarian tumors manifesting double-stranded DNA-repair defects, whereas tankyrase 1 and 2 (TNKS1 and TNKS2, also known as PARP5a and PARP5b, respectively) inhibitors have been developed for tumors with elevated ?-catenin activity. As the clinical relevance of PARP inhibitors continues to be actively explored, there is heightened interest in the design of selective inhibitors based on the detailed structural features of how small-molecule inhibitors bind to each of the PARP family members. Here, the high-resolution crystal structures of the human TNKS2 PARP domain in complex with 16 various PARP inhibitors are reported, including the compounds BSI-201, AZD-2281 and ABT-888, which are currently in Phase 2 or 3 clinical trials. These structures provide insight into the inhibitor-binding modes for the tankyrase PARP domain and valuable information to guide the rational design of future tankyrase-specific inhibitors.

  20. The structure of the SBP-Tagstreptavidin complex reveals a novel helical scaffold bridging binding pockets on separate subunits

    SciTech Connect (OSTI)

    Barrette-Ng, Isabelle H.; Wu, Sau-Ching; Tjia, Wai-Mui; Wong, Sui-Lam; Ng, Kenneth K. S.

    2013-05-01

    The structure of the SBP-Tagstreptavidin complex reveals a novel mode of peptide recognition in which a single peptide binds simultaneously to biotin-binding pockets from adjacent subunits of streptavidin. The molecular details of peptide recognition suggest how the SBP-Tag can be further modified to become an even more useful tag for a wider range of biotechnological applications. The 38-residue SBP-Tag binds to streptavidin more tightly (K{sub d} ? 2.54.9 nM) than most if not all other known peptide sequences. Crystallographic analysis at 1.75 resolution shows that the SBP-Tag binds to streptavidin in an unprecedented manner by simultaneously interacting with biotin-binding pockets from two separate subunits. An N-terminal HVV peptide sequence (residues 1214) and a C-terminal HPQ sequence (residues 3133) form the bulk of the direct interactions between the SBP-Tag and the two biotin-binding pockets. Surprisingly, most of the peptide spanning these two sites (residues 1728) adopts a regular ?-helical structure that projects three leucine side chains into a groove formed at the interface between two streptavidin protomers. The crystal structure shows that residues 110 and 3538 of the original SBP-Tag identified through in vitro selection and deletion analysis do not appear to contact streptavidin and thus may not be important for binding. A 25-residue peptide comprising residues 1134 (SBP-Tag2) was synthesized and shown using surface plasmon resonance to bind streptavidin with very similar affinity and kinetics when compared with the SBP-Tag. The SBP-Tag2 was also added to the C-terminus of ?-lactamase and was shown to be just as effective as the full-length SBP-Tag in affinity purification. These results validate the molecular structure of the SBP-Tagstreptavidin complex and establish a minimal bivalent streptavidin-binding tag from which further rational design and optimization can proceed.

  1. A van der Waals density functional study of adenine on graphene: Single molecular adsorption and overlayer binding

    SciTech Connect (OSTI)

    Berland, Kristian [Chalmers University of Technology, Sweden; Cooper, Valentino R [ORNL; Langreth, David C. [Rutgers University; Schroder, Prof. Elsebeth [Chalmers University of Technology, Sweden; Chakarova-Kack, Svetla [Chalmers University of Technology, Sweden

    2011-01-01

    The adsorption of an adenine molecule on graphene is studied using a first-principles van der Waals functional (vdW-DF) [Dion et al., Phys. Rev. Lett. 92, 246401 (2004)]. The cohesive energy of an ordered adenine overlayer is also estimated. For the adsorption of a single molecule, we determine the optimal binding configuration and adsorption energy by translating and rotating the molecule. The adsorption energy for a single molecule of adenine is found to be 711 meV, which is close to the calculated adsorption energy of the similar-sized naphthalene. Based on the single molecular binding configuration, we estimate the cohesive energy of a two-dimensional ordered overlayer. We find a significantly stronger binding energy for the ordered overlayer than for single-molecule adsorption.

  2. Cationic Gold Clusters Ligated with Differently Substituted Phosphines: Effect of Substitution on Ligand Reactivity and Binding

    SciTech Connect (OSTI)

    Johnson, Grant E.; Olivares, Astrid M.; Hill, David E.; Laskin, Julia

    2015-01-01

    We present a systematic study of the effect of the number of methyl (Me) and cyclohexyl (Cy) functional groups in monodentate phosphine ligands on the solution-phase synthesis of ligated sub-nanometer gold clusters and their gas-phase fragmentation pathways. Small mixed ligand cationic gold clusters were synthesized using ligand exchange reactions between pre-formed triphenylphosphine ligated (PPh3) gold clusters and monodentate Me- and Cy-substituted ligands in solution and characterized using electrospray ionization mass spectrometry (ESI-MS) and collision-induced dissociation (CID) experiments. Under the same experimental conditions, larger gold-PPh3 clusters undergo efficient exchange of unsubstituted PPh3 ligands for singly Me- and Cy-substituted PPh2Me and PPh2Cy ligands. The efficiency of ligand exchange decreases with an increasing number of Me or Cy groups in the substituted phosphine ligands. CID experiments performed for a series of ligand-exchanged gold clusters indicate that loss of a neutral Me-substituted ligand is preferred over loss of a neutral PPh3 ligand while the opposite trend is observed for Cy-substituted ligands. The branching ratio of the competing ligand loss channels is strongly correlated with the electron donating ability of the phosphorous lone pair as determined by the relative proton affinity of the ligand. The results indicate that the relative ligand binding energies increase in the order PMe3 < PPhMe2 < PPh2Me < PPh3< PPh2Cy < PPhCy2< PCy3. Furthermore, the difference in relative ligand binding energies increases with the number of substituted PPh3-mMem or PPh3-mCym ligands (L) exchanged onto each cluster. This study provides the first experimental determination of the relative binding energies of ligated gold clusters containing differently substituted monophosphine ligands, which are important to controlling their synthesis and reactivity in solution. The results also indicate that ligand substitution is an important parameter that must be considered in theoretical modeling of these complex systems

  3. The impacts of electronic state hybridization on the binding energy of single phosphorus donor electrons in extremely downscaled silicon nanostructures

    SciTech Connect (OSTI)

    The Anh, Le Manoharan, Muruganathan; Moraru, Daniel; Tabe, Michiharu; Mizuta, Hiroshi

    2014-08-14

    We present the density functional theory calculations of the binding energy of the Phosphorus (P) donor electrons in extremely downscaled single P-doped Silicon (Si) nanorods. In past studies, the binding energy of donor electrons was evaluated for the Si nanostructures as the difference between the ionization energy for the single P-doped Si nanostructures and the electron affinity for the un-doped Si nanostructures. This definition does not take into account the strong interaction of donor electron states and Si electron states explicitly at the conductive states and results in a monotonous increase in the binding energy by reducing the nanostructure's dimensions. In this paper, we introduce a new approach to evaluate the binding energy of donor electrons by combining the projected density of states (PDOS) analysis and three-dimensional analysis of associated electron wavefunctions. This enables us to clarify a gradual change of the spatial distribution of the 3D electron wavefunctions (3DWFs) from the donor electron ground state, which is fully localized around the P donor site to the first conductive state, which spreads over the outer Si nanorods contributing to current conduction. We found that the energy of the first conductive state is capped near the top of the atomistic effective potential at the donor site with respect to the surrounding Si atoms in nanorods smaller than about 27 a{sub 0}. This results in the binding energy of approximately 1.5?eV, which is virtually independent on the nanorod's dimensions. This fact signifies a good tolerance of the binding energy, which governs the operating temperature of the single dopant-based transistors in practice. We also conducted the computationally heavy transmission calculations of the single P-doped Si nanorods connected to the source and drain electrodes. The calculated transmission spectra are discussed in comparison with the atomistic effective potential distributions and the PDOS-3DWFs method.

  4. Dependence of Nuclear Binding Energies on the Cutoff Momentum of Low-Momentum Nucleon-Nucleon Interaction

    E-Print Network [OSTI]

    S. Fujii; H. Kamada; R. Okamoto; K. Suzuki

    2004-06-30

    Binding energies of ^{3}H, ^{4}He, and ^{16}O are calculated, using low-momentum nucleon-nucleon interactions (V_{low-k}) for a wide range of the cutoff momentum \\Lambda. In addition, single-particle energies in nuclei around ^{16}O are computed. The dependence of the binding energies and the single-particle energies in these nuclei on the cutoff momentum \\Lambda of the V_{low-k} is examined. Furthermore, the availability of the V_{low-k} in nuclear structure calculations is discussed.

  5. A Simple Efficient Method for Obtaining the Binding Energy of Lithium Nucleus under the Hulthn and Inversely Quadratic Yukawa Potentials

    E-Print Network [OSTI]

    Nasrin. Salehi; Mahsa. Ghazvini

    2015-04-28

    In this paper, the binding energy of Lithium nucleus in a nonrelativistic model is obtained for the Hulth\\'en and the Inversely Quadratic Yukawa Potential. In order to that, we used the concept of supersymmetry to solving the Schr\\"odinger equation exact analytically. These potentials, due to their physical interpretations, are of interest within many areas of theoretical physics. The results of our model for all calculations show that the ground state binding energy of Lithium nucleus with these potentials are very close to the ones obtained in experiments.

  6. CO2-Binding Organic Liquids, an Integrated Acid Gas Capture System

    SciTech Connect (OSTI)

    Heldebrant, David J.; Koech, Phillip K.; Rainbolt, James E.; Zheng, Feng

    2011-04-01

    Amine systems are effective for CO2 capture, but they are still inefficient because the solvent regeneration energy is largely defined by the amount of water in the process. Most amines form heat-stable salts with SO2 and COS resulting in parasitic solvent loss and degradation. Stripping the CO2-rich solvent is energy intensive it requires temperatures above 100 ?C due to the high specific heat and heat of vaporization of water. CO2-capture processes could be much more energy efficient in a water free amine process. In addition, if the capture-material is chemically compatible with other acid gases, less solvent would be lost to heat-stable salts and the process economics would be further improved. One such system that can address these concerns is Binding Organic Liquids (BOLs), a class of switchable ionic liquids.

  7. Hybrid Monte-Carlo simulation of interacting tight-binding model of graphene

    E-Print Network [OSTI]

    Dominik Smith; Lorenz von Smekal

    2013-11-05

    In this work, results are presented of Hybrid-Monte-Carlo simulations of the tight-binding Hamiltonian of graphene, coupled to an instantaneous long-range two-body potential which is modeled by a Hubbard-Stratonovich auxiliary field. We present an investigation of the spontaneous breaking of the sublattice symmetry, which corresponds to a phase transition from a conducting to an insulating phase and which occurs when the effective fine-structure constant $\\alpha$ of the system crosses above a certain threshold $\\alpha_C$. Qualitative comparisons to earlier works on the subject (which used larger system sizes and higher statistics) are made and it is established that $\\alpha_C$ is of a plausible magnitude in our simulations. Also, we discuss differences between simulations using compact and non-compact variants of the Hubbard field and present a quantitative comparison of distinct discretization schemes of the Euclidean time-like dimension in the Fermion operator.

  8. Effective tight-binding model for MX2 under electric and magnetic fields

    SciTech Connect (OSTI)

    Kavungal Veedu, Shanavas [ORNL; Satpathy, S [University of Missouri, Columbia

    2015-01-01

    We present a systematic method for developing a five band Hamiltonian for the metal d orbitals that can be used to study the effect of electric and magnetic fields on multilayer MX2 (M=Mo,W and X=S,Se) systems. On a hexagonal lattice of d orbitals, the broken inversion symmetry of the monolayers is incorporated via fictitious s orbitals at the chalcogenide sites. A tight-binding Hamiltonian is constructed and then downfolded to get effective d orbital overlap parameters using quasidegenerate perturbation theory. The steps to incorporate the effects of multiple layers, external electric and magnetic fields are also detailed. We find that an electric field produces a linear-k Rashba splitting around the point, while a magnetic field removes the valley pseudospin degeneracy at the K points. Our model provides a simple tool to understand the recent experiments on electric and magnetic control of valley pseudospin in monolayer dichalcogendies.

  9. Benchmark Theoretical Study of the ?? Binding Energy in the Benzene Dimer

    SciTech Connect (OSTI)

    Miliordos, Evangelos; Apra, Edoardo; Xantheas, Sotiris S.

    2014-09-04

    We establish a new estimate for the interaction energy between two benzene molecules in the parallel displaced (PD) conformation by systematically converging (i) the intra- and intermolecular geometry at the minimum geometry, (ii) the expansion of the orbital basis set and (iii) the level of electron correlation. The calculations were performed at the second order Mller - Plesset perturbation (MP2) and the Coupled Cluster including Singles, Doubles and a perturbative estimate of Triples replacements [CCSD(T)] levels of electronic structure theory. At both levels of theory, by including results corrected for Basis Set Superposition Error (BSSE), we have estimated the Complete Basis Set (CBS) limit by employing the family of Dunnings correlation consistent polarized valence basis sets. The largest MP2 calculation was performed with the cc-pV6Z basis set (2,772 basis functions), whereas the largest CCSD(T) calculation with the cc-pV5Z basis set (1,752 basis functions). The cluster geometries were optimized with basis sets up to quadruple-? quality, observing that both its intra- and inter-molecular parts have practically converged with the triple-? quality sets. The use of converged geometries was found to play an important role for obtaining accurate estimates for the CBS limits. Our results demonstrate that the binding energies with the families of the plain (cc-pVnZ) and augmented (aug-cc-pVnZ) sets converge [to within < 0.01 kcal/mol for MP2 and < 0.15 kcal/mol for CCSD(T)] to the same CBS limit. In addition, the average of the uncorrected and BSSEcorrected binding energies was found to converge to the same CBS limit must faster than either of the two constituents (uncorrected or BSSE-corrected binding energies). Due to the fact that the family of augmented basis sets (especially for the larger sets) causes serious linear dependency problems, the plain basis sets (for which no linear dependencies were found) are deemed as a more efficient and straightforward path for obtaining an accurate CBS limit. We considered extrapolations of the uncorrected (?𝐸) and BSSE-corrected (?𝐸!") binding energies, their average value (?𝐸!"#) as well as the average of the latter over the plain and augmented sets (?𝐸!"#) with the cardinal number of the basis set n. Our best estimate of the CCSD(T)/CBS limit for the ?-? interaction energy in the PD benzene dimer is De = 2.65 0.02 kcal/mol. The best CCSD(T)/cc-pV5Z calculated value is 2.62 kcal/mol, just 0.03 kcal/mol away from the CBS limit. For comparison, the MP2/CBS limit estimate is 5.00 0.01 kcal/mol, demonstrating a 90% overbinding with respect to CCSD(T). The Spin-Component-Scaled (SCS) MP2 variant was found to closely reproduce the CCSD(T) results for each basis set, while Scaled-Opposite-Spin (SOS) yielded results that are too low when compared to CCSD(T).

  10. Atypical Response Regulator ChxR from Chlamydia trachomatis Is Structurally Poised for DNA Binding

    E-Print Network [OSTI]

    Barta, Michael L.; Hickey, John Michael; Anbanandam, Asokan; Dyer, Kevin; Hammel, Michal; Hefty, P. Scott

    2014-03-19

    ] and are as follows: PhoB (1QQI); YycF (2D1V); HP1043 (2HQR); OmpR (2JPB); PhoP (2PMU); KdpE (3ZQ7) for effector domains and DrrD (1KGS); DrrB (1P2F); PrrA (1YS6); MtrA (2GWR); HP1043 (2HQR); RegX3 (2OQR); PhoP (3R0J) for full-length structures. Representations of all... in the chxR promoter with a dissociation constant (Kd) of approximately 44 nM [17]. To determine if ChxREff (residues 115227) alone can to bind to DNA, an electrophoretic mobility Table 2. SAXS Parameters for Data Validation and Interpretation. SAXS...

  11. CO2 Binding Organic Liquids Gas Capture with Polarity Swing Assisted Regeneration

    SciTech Connect (OSTI)

    Heldebrant, David

    2014-05-31

    This report outlines the comprehensive bench-scale testing of the CO2-binding organic liquids (CO2BOLs) solvent platform and its unique Polarity Swing Assisted Regeneration (PSAR). This study outlines all efforts on a candidate CO2BOL solvent molecule, including solvent synthesis, material characterization, preliminary toxicology studies, and measurement of all physical, thermodynamic and kinetic data, including bench-scale testing. Equilibrium and kinetic models and analysis were made using Aspen Plus. Preliminary process configurations, a technoeconomic assessment and solvent performance projections for separating CO2 from a subcritical coal-fired power plant are compared to the U.S. Department of Energy's Case 10 monoethanolamine baseline.

  12. Of Bulk and Boundaries: Generalized Transfer Matrices for Tight-Binding Models

    E-Print Network [OSTI]

    Vatsal Dwivedi; Victor Chua

    2015-10-14

    We construct a generalized transfer matrix corresponding to noninteracting tight-binding lattice models, which can subsequently be used to compute the bulk bands as well as the edge states. Crucially, our formalism works even in cases where the hopping matrix is non-invertible. Following Hatsugai [PRL 71, 3697 (1993)], we explicitly construct the energy Riemann surfaces associated with the band structure for a specific class of systems which includes systems like Chern insulator, Dirac semimetal and graphene. The edge states can then be interpreted as non-contractible loops, with the winding number equal to the bulk Chern number. For these systems, the transfer matrix is symplectic, and hence we also describe the windings associated with the edge states on $Sp(2, \\mathbb{R})$ and interpret the corresponding winding number as a Maslov index.

  13. Of Bulk and Boundaries: Generalized Transfer Matrices for Tight-Binding Models

    E-Print Network [OSTI]

    Vatsal Dwivedi; Victor Chua

    2015-10-26

    We construct a generalized transfer matrix corresponding to noninteracting tight-binding lattice models, which can subsequently be used to compute the bulk bands as well as the edge states. Crucially, our formalism works even in cases where the hopping matrix is non-invertible. Following Hatsugai [PRL 71, 3697 (1993)], we explicitly construct the energy Riemann surfaces associated with the band structure for a specific class of systems which includes systems like Chern insulator, Dirac semimetal and graphene. The edge states can then be interpreted as non-contractible loops, with the winding number equal to the bulk Chern number. For these systems, the transfer matrix is symplectic, and hence we also describe the windings associated with the edge states on $Sp(2, \\mathbb{R})$ and interpret the corresponding winding number as a Maslov index.

  14. Ab initio study of formation, migration and binding properties of helium-vacancy clusters in aluminum

    SciTech Connect (OSTI)

    Yang, Li; Zu, Xiaotao T.; Gao, Fei

    2008-08-01

    Ab initio calculations based on density functional theory have been performed to study the dissolution and migration of helium, and the stability of small helium-vacancy clusters HenVm (n, m=0 to 4) in aluminum. The results indicate that the octahedral configuration is more stable than the tetrahedral. Interstitial helium atoms are predicted to have attractive interactions and jump between two octahedral sites via an intermediate tetrahedral site with low migration energy of 0.10 eV. The binding energies of an interstitial He atom and an isolated vacancy to a HenVm cluster are also obtained from the calculated formation energies of the clusters. We find that the divacancy and tri--vacancy clusters are not stable, but He atoms can increase the stability of vacancy clusters. The interactions of He atoms with a vacancy are found to be in good agreement with the experimental results.

  15. Characterization of alternate reductant binding and electron transfer in the dopamine. beta. -monooxygenase reaction

    SciTech Connect (OSTI)

    Stewart, L.C.; Klinman, J.P.

    1987-08-25

    The steady-state limiting kinetic parameters V/sub max/, V/K/sub DA/, and V/K/sub O/sub 2//, together with deuterium isotope effects on these parameters, have been determined for the dopamine ..beta..-monooxygenase (D..beta..M) reaction in the presence of structurally distinct reductants. The results show the one-electron reductant ferrocyanide to be nearly as kinetically competent as the presumed in vivo reductant ascrobate. Further, a reductant system of ferricyanide plus substrate dopamine yields steady-state kinetic parameters and isotope effects very similar to those measured solely in the presence of ferrocyanide, indicating a role for catecholamine in the rapid recycling of oxidized ferrocyanide. Use of substrate dopamine as the sole reductant is found to lead to a highly unusual kinetic independence of oxygen concentration, as well as significantly reduced values of V/sub max/ and V/K/sub DA/, and the authors conclude that dopamine reduces enzymic copper in a rate-limiting step that is 40-fold slower than with ascorbate. The near-identical kinetic parameters measured in the presence of either ascorbate or ferrocyanide, together with markedly reduced rates with dopamine, are interpreted in terms of a binding site for reductant that is physically distinct from the substrate binding site. This view is supported by molecular modeling, which reveals ascorbate and ferrocyanide to possess an unexpected similarity in potential sites for interaction with enzymic residues. With regard to electron flux, identical values of V/K/sub O/sub 2// have been measured with (2,2-/sup 2/H/sub 2/)dopamine as substrate both in the presence and in the absence of added ascorbate. This key result unambiguously rules out an entry of electrons to enzyme forms leading from the enzyme-dopamine complex to enzyme-bound product and, hence, reaction mechanisms involving a reductive activation of the putative Cu(II)-OOH prior to substrate hydroxylation.

  16. Surface structural ion adsorption modeling of competitive binding of oxyanions by metal (hydr)oxides

    SciTech Connect (OSTI)

    Hiemstra, T.; Riemsdijk, W.H. van

    1999-02-01

    An important challenge in surface complexation models (SCM) is to connect the molecular microscopic reality to macroscopic adsorption phenomena. This study elucidates the primary factor controlling the adsorption process by analyzing the adsorption and competition of PO{sub 4}, AsO{sub 4}, and SeO{sub 3}. The authors show that the structure of the surface-complex acting in the dominant electrostatic field can be ascertained as the primary controlling adsorption factor. The surface species of arsenate are identical with those of phosphate and the adsorption behavior is very similar. On the basis of the selenite adsorption, The authors show that the commonly used 1pK models are incapable to incorporate in the adsorption modeling the correct bidentate binding mechanism found by spectroscopy. The use of the bidentate mechanism leads to a proton-oxyanion ratio and corresponding pH dependence that are too large. The inappropriate intrinsic charge attribution to the primary surface groups and the condensation of the inner sphere surface complex to a point charge are responsible for this behavior of commonly used 2pK models. Both key factors are differently defined in the charge distributed multi-site complexation (CD-MUSIC) model and are based in this model on a surface structural approach. The CD-MUSIC model can successfully describe the macroscopic adsorption phenomena using the surface speciation and binding mechanisms as found by spectroscopy. The model is also able to predict the anion competition well. The charge distribution in the interface is in agreement with the observed structure of surface complexes.

  17. Haematopoietic malignancies caused by dysregulation of a chromatin-binding PHD finger

    SciTech Connect (OSTI)

    Wang, Gang G.; Song, Jikui; Wang, Zhanxin; Dormann, Holger L.; Casadio, Fabio; Li, Haitao; Luo, Jun-Li; Patel, Dinshaw J.; Allis, C. David; (MSKCC); (Scripps); (Rockefeller)

    2009-07-21

    Histone H3 lysine4 methylation (H3K4me) has been proposed as a critical component in regulating gene expression, epigenetic states, and cellular identities. The biological meaning of H3K4me is interpreted by conserved modules including plant homeodomain (PHD) fingers that recognize varied H3K4me states. The dysregulation of PHD fingers has been implicated in several human diseases, including cancers and immune or neurological disorders. Here we report that fusing an H3K4-trimethylation (H3K4me3)-binding PHD finger, such as the carboxy-terminal PHD finger of PHF23 or JARID1A (also known as KDM5A or RBBP2), to a common fusion partner nucleoporin-98 (NUP98) as identified in human leukaemias, generated potent oncoproteins that arrested haematopoietic differentiation and induced acute myeloid leukaemia in murine models. In these processes, a PHD finger that specifically recognizes H3K4me3/2 marks was essential for leukaemogenesis. Mutations in PHD fingers that abrogated H3K4me3 binding also abolished leukaemic transformation. NUP98-PHD fusion prevented the differentiation-associated removal of H3K4me3 at many loci encoding lineage-specific transcription factors (Hox(s), Gata3, Meis1, Eya1 and Pbx1), and enforced their active gene transcription in murine haematopoietic stem/progenitor cells. Mechanistically, NUP98-PHD fusions act as 'chromatin boundary factors', dominating over polycomb-mediated gene silencing to 'lock' developmentally critical loci into an active chromatin state (H3K4me3 with induced histone acetylation), a state that defined leukaemia stem cells. Collectively, our studies represent, to our knowledge, the first report that deregulation of the PHD finger, an 'effector' of specific histone modification, perturbs the epigenetic dynamics on developmentally critical loci, catastrophizes cellular fate decision-making, and even causes oncogenesis during mammalian development.

  18. Calculation of absolute free energy of binding for theophylline and its analogs to RNA aptamer using nonequilibrium work values

    E-Print Network [OSTI]

    Yoshiaki Tanida; Masakatsu Ito; Hideaki Fujitani

    2007-08-06

    The massively parallel computation of absolute binding free energy with a well-equilibrated system (MP-CAFEE) has been developed [H. Fujitani, Y. Tanida, M. Ito, G. Jayachandran, C. D. Snow, M. R. Shirts, E. J. Sorin, and V. S. Pande, J. Chem. Phys. ${\\bf 123}$, 084108 (2005)]. As an application, we perform the binding affinity calculations of six theophylline-related ligands with RNA aptamer. Basically, our method is applicable when using many compute nodes to accelerate simulations, thus a parallel computing system is also developed. To further reduce the computational cost, the adequate non-uniform intervals of coupling constant $\\lambda$, connecting two equilibrium states, namely bound and unbound, are determined. The absolute binding energies $\\Delta G$ thus obtained have effective linear relation between the computed and experimental values. If the results of two other different methods are compared, thermodynamic integration (TI) and molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) by the paper of Gouda $et al$ [H. Gouda, I. D. Kuntz, D. A. Case, and P. A. Kollman, Biopolymers ${\\bf 68}$, 16 (2003)], the predictive accuracy of the relative values $\\Delta\\Delta G$ is almost comparable to that of TI: the correlation coefficients (R) obtained are 0.99 (this work), 0.97 (TI), and 0.78 (MM-PBSA). On absolute binding energies meanwhile, a constant energy shift of $\\sim$ -7 kcal/mol against the experimental values is evident. To solve this problem, several presumable reasons are investigated.

  19. NMR Structures of Salt-Refolded Forms of the 434-Repressor DNA-Binding Domain in 6 M Urea

    E-Print Network [OSTI]

    Wider, Gerhard

    NMR Structures of Salt-Refolded Forms of the 434-Repressor DNA-Binding Domain in 6 M Urea- 8). Examples are salt-induced refolding of proteins at acidic pH (9), leading to the formation), and lysozyme (14) allowed detailed structural and dynamic characterization of salt-stabilized A-states, which

  20. Crystal and solution structures of an odorant-binding protein from the southern house mosquito complexed with an oviposition pheromone

    SciTech Connect (OSTI)

    Mao, Yang; Xu, Xianzhong; Xu, Wei; Ishida, Yuko; Leal, Walter S.; Ames, James B.; Clardy, Jon

    2010-11-15

    Culex mosquitoes introduce the pathogens responsible for filariasis, West Nile virus, St. Louis encephalitis, and other diseases into humans. Currently, traps baited with oviposition semiochemicals play an important role in detection efforts and could provide an environmentally friendly approach to controlling their populations. The odorant binding proteins (OBPs) in the female's antenna play a crucial, if yet imperfectly understood, role in sensing oviposition cues. Here, we report the X-ray crystallography and NMR 3D structures of OBP1 for Culex quinquefasciatus (CquiOBP1) bound to an oviposition pheromone (5R,6S)-6-acetoxy-5-hexadecanolide (MOP). In both studies, CquiOBP1 had the same overall six-helix structure seen in other insect OBPs, but a detailed analysis revealed an important previously undescribed feature. There are two models for OBP-mediated signal transduction: (i) direct release of the pheromone from an internal binding pocket in a pH-dependent fashion and (ii) detection of a pheromone-induced conformational change in the OBP {center_dot} pheromone complex. Although CquiOBP1 binds MOP in a pH-dependent fashion, it lacks the C terminus required for the pH-dependent release model. This study shows that CquiOBP binds MOP in an unprecedented fashion using both a small central cavity for the lactone head group and a long hydrophobic channel for its tail.

  1. Calculations of pH-Dependent Binding of Proteins to Biological Membranes Maja Mihajlovic and Themis Lazaridis*

    E-Print Network [OSTI]

    Lazaridis, Themis

    Lazaridis* Department of Chemistry, City College of the City UniVersity of New York, New York, New York energies. The standard free energy of binding, G, is defined as -RT ln(Pb/Pf), where Pb and Pf free energy are (a) the free energy cost of ionization state changes (Gion), (b) the effective energy

  2. Biochemistry 1990, 29, 6043-6050 6043 Detection of Drug Binding to DNA by Hydroxyl Radical Footprinting.

    E-Print Network [OSTI]

    Tullius, Thomas D.

    Biochemistry 1990, 29, 6043-6050 6043 Detection of Drug Binding to DNA by Hydroxyl Radical Manuscript Received March 29, 1990 ABSTRACT: We report the use of hydroxyl radical footprinting to analyze difference in the hydroxyl radical footprints of the two drugs. Distamycin gives a conventional (albeit high

  3. Synthesis, Characterization, and Preliminary Host-Guest Binding Studies of Porphyrinic Molecular Squares Featuring fac-Tricarbonylrhenium(I) Chloro Corners

    E-Print Network [OSTI]

    as solution-phase hosts for either complex anionic guests3a or neutral aromatic guests where binding, adding a 5 mL volume of saturated ZnII acetate in methanol, and stirring for 4 h. 3 was precipitated by adding a large volume of methanol/water mixture. The product was isolated by vacuum-filtration, washed

  4. Hydrogen Bonds Involved in Binding the Qi-site Semiquinone in the bc1 Complex, Identified through Deuterium Exchange

    E-Print Network [OSTI]

    Crofts, Antony R.

    Hydrogen Bonds Involved in Binding the Qi-site Semiquinone in the bc1 Complex, Identified through them. The strength of interactions indicates that the protons are involved in hydrogen bonds with SQ. The hyperfine cou- plings differ from values typical for in-plane hydrogen bonds previously observed in model

  5. Use of Cre/loxP recombination to swap cell binding motifs on the adenoviral capsid protein IX

    SciTech Connect (OSTI)

    Poulin, Kathy L.; Tong, Grace; Vorobyova, Olga; Pool, Madeline; Kothary, Rashmi; Parks, Robin J.

    2011-11-25

    We used Cre/loxP recombination to swap targeting ligands present on the adenoviral capsid protein IX (pIX). A loxP-flanked sequence encoding poly-lysine (pK-binds heparan sulfate proteoglycans) was engineered onto the 3'-terminus of pIX, and the resulting fusion protein allowed for routine virus propagation. Growth of this virus on Cre-expressing cells removed the pK coding sequence, generating virus that could only infect through alternative ligands, such as a tyrosine kinase receptor A (TrkA)-binding motif engineered into the capsid fibre protein for enhanced infection of neuronal cells. We used a similar approach to swap the pK motif on pIX for a sequence encoding a single-domain antibody directed towards CD66c for targeted infection of cancer cells; Cre-mediated removal of the pK-coding sequence simultaneously placed the single-domain antibody coding sequence in frame with pIX. Thus, we have developed a simple method to propagate virus lacking native viral tropism but containing cell-specific binding ligands. - Highlights: > We describe a method to grow virus lacking native tropism but containing novel cell-binding ligands. > Cre/loxP recombination was used to modify the adenovirus genome. > A targeting ligand present on capsid protein IX was removed or replaced using recombination. > Cre-loxP was also used to 'swap' the identity of the targeting ligand present on pIX.

  6. A Double-Deletion Method to Quantifying Incremental Binding Energies in Proteins from Experiment: Example of a Destabilizing Hydrogen

    E-Print Network [OSTI]

    Sancho, Javier

    A Double-Deletion Method to Quantifying Incremental Binding Energies in Proteins from Experiment: Example of a Destabilizing Hydrogen Bonding Pair Luis A. Campos,*y Santiago Cuesta-Lopez,*z Jon Lo of a specific hydrogen bond in apoflavodoxin to protein stability is investigated by combining theory

  7. The tip of the iceberg: RNA-binding proteins with prion-like domains in neurodegenerative disease

    E-Print Network [OSTI]

    Shorter, James

    ) and a putative prion do- main. Indeed, of 210 human RRM-bearing proteins, 29 have a putative prion domain, and 12 1st and 10th among RRM-bearing prion candidates, form cytoplasmic inclusions in the degenerating RNA-binding proteostasis of TAF15, which is the 2nd ranked RRM-bearing prion candidate, has been con

  8. Calcium-regulated DNA Binding and Oligomerization of the Neuronal Calcium-sensing Protein, Calsenilin/DREAM/KChIP3*

    E-Print Network [OSTI]

    Ikura, Mitsuhiko

    and forms a tetramer at concentra- tions above 200 M. The Ca2 -free protein is a tetramer that the Ca2 -free protein tetramer binds endothermi- cally ( H 25 kcal/mol) to four molecules of DNA derived- lated and sequence-specific fashion. The C-terminal fragment is a tetramer in the Ca2 -free state

  9. The myosin motor, Myo4p, binds Ash1 mRNA via the adapter protein, She3p

    E-Print Network [OSTI]

    Vale, Ronald D.

    The myosin motor, Myo4p, binds Ash1 mRNA via the adapter protein, She3p Peter A. Takizawa) In Saccharomyces cerevisiae, mRNA encoding the cell-fate deter- minant Ash1p is localized to the distal tip of daughter cells. Five SHE genes are required for proper Ash1 mRNA localization, one of which encodes

  10. Forskolin- and dihydroalprenolol (DHA) binding sites and adenylate cyclase activity in heart of rats fed diets containing different oils

    SciTech Connect (OSTI)

    Alam, S.Q.; Ren, Y.F.; Alam, B.S.

    1987-05-01

    The purpose of the present investigation was to determine if dietary lipids can induce changes in the adenylate cyclase system in rat heart. Three groups of male young Sprague-Dawley rats were fed for 6 weeks diets containing 10% corn oil (I), 8% coconut oil + 2% corn oil (II) or 10% menhaden oil (III). Adenylate cyclase activity (basal, fluoride-, isoproterenol-, and forskolin-stimulated) was higher in heart homogenates of rats in group III than in the other two groups. Concentration of the (/sup 3/H)-forskolin binding sites in the cardiac membranes were significantly higher in rats fed menhaden oil. The values (pmol/mg protein) were 4.8 +/- 0.2 (I), 4.5 +/- 0.7 (II) and 8.4 +/- 0.5 (III). There was no significant difference in the affinity of the forskolin binding sites among the 3 dietary groups. When measured at different concentrations of forskolin, the adenylate cyclase activity in cardiac membranes of rats fed menhaden oil was higher than in the other 2 groups. Concentrations of the (/sup 3/H)DHA binding sites were slightly higher but their affinity was lower in cardiac membranes of rats fed menhaden oil. The results suggest that diets containing fish oil increase the concentration of the forskolin binding sites and may also affect the characteristics of the ..beta..-adrenergic receptor in rat heart.

  11. Metal Ion Binding and Enzymatic Mechanism of Methanococcus jannaschii RNase Bing Lai, Ying Li, Aoneng Cao, and Luhua Lai*

    E-Print Network [OSTI]

    Luhua, Lai

    Metal Ion Binding and Enzymatic Mechanism of Methanococcus jannaschii RNase HII Bing Lai, Ying Li the RNA moiety in DNA:RNA hybrid in a divalent metal ion dependent manner. It is essential to understand the role of metal ion in enzymatic mechanism. One of the key points in this study is how many metal ions

  12. Mutation of the Fiber Shaft Heparan Sulphate Binding Site of a 5/3 Chimeric Adenovirus Reduces Liver Tropism

    E-Print Network [OSTI]

    Hemminki, Akseli

    Mutation of the Fiber Shaft Heparan Sulphate Binding Site of a 5/3 Chimeric Adenovirus Reduces and to cellular heparan sulphate proteoglycans via the fiber shaft KKTK domain are suggested to cause liver. Citation: Koski A, Karli E, Kipar A, Escutenaire S, Kanerva A, et al. (2013) Mutation of the Fiber Shaft

  13. Structure of N-Terminal Domain of NPC1 Reveals Distinct Subdomains for Binding and Transfer of Cholesterol

    SciTech Connect (OSTI)

    Kwon, Hyock Joo; Abi-Mosleh, Lina; Wang, Michael L.; Deisenhofer, Johann; Goldstein, Joseph L.; Brown, Michael S.; Infante, Rodney E.

    2010-09-21

    LDL delivers cholesterol to lysosomes by receptor-mediated endocytosis. Exit of cholesterol from lysosomes requires two proteins, membrane-bound Niemann-Pick C1 (NPC1) and soluble NPC2. NPC2 binds cholesterol with its isooctyl side chain buried and its 3{beta}-hydroxyl exposed. Here, we describe high-resolution structures of the N-terminal domain (NTD) of NPC1 and complexes with cholesterol and 25-hydroxycholesterol. NPC1(NTD) binds cholesterol in an orientation opposite to NPC2: 3{beta}-hydroxyl buried and isooctyl side chain exposed. Cholesterol transfer from NPC2 to NPC1(NTD) requires reorientation of a helical subdomain in NPC1(NTD), enlarging the opening for cholesterol entry. NPC1 with point mutations in this subdomain (distinct from the binding subdomain) cannot accept cholesterol from NPC2 and cannot restore cholesterol exit from lysosomes in NPC1-deficient cells. We propose a working model wherein after lysosomal hydrolysis of LDL-cholesteryl esters, cholesterol binds NPC2, which transfers it to NPC1(NTD), reversing its orientation and allowing insertion of its isooctyl side chain into the outer lysosomal membranes.

  14. Binding and Recognition in the Assembly of an Active BRCA1/BARD1 Ubiquitin-Ligase Complex

    SciTech Connect (OSTI)

    Brzovic, Peter S.; Keeffe, Jennifer R.; Nishikawa, Hiroyuki; Miyamoto, Keiko; Fox, David; Fukuda, Mamoru; Ohta, Tomohiko; Klevit, Rachel E.

    2003-05-13

    BRCA1 is a breast and ovarian cancer tumor suppressor protein that associates with BARD1 to form a RING/RING heterodimer. The BRCA1/BARD1 RING complex functions as an ubiquitin (Ub) ligase with activity substantially greater than individual BRCA1 or BARD1 subunits. By using NMR spectroscopy and site-directed mutagenesis, we have mapped the binding site on the BRCA1/BARD1 heterodimer for the Ub-conjugating enzyme UbcH5c. The results demonstrate that UbcH5c binds only to the BRCA1 RING domain and not the BARD1 RING. The binding interface is formed by the first and second Zn2+-loops and central -helix of the BRCA1 RING domain, a region disrupted by cancer-predisposing mutations. Unexpectedly, a second Ub-conjugating enzyme, UbcH7, also interacts with the BRCA1/BARD1 complex with similar affinity, although it is not active in Ub-ligase activity assays. Thus, binding alone is not sufficient for BRCA1-dependent Ub-ligase activity.

  15. Portland Area Book Binding Resources This is the binder that has provided services in the past to the library

    E-Print Network [OSTI]

    Chapman, Michael S.

    .E. Belmont St., Portland. (503) 233-2248 Copyman (http://www.copymanportland.com/), 1242 S.W. 11th Ave://www.fedex.com/us/office/binding-finishing-laminating.html) multiple locations GISI Marketing, (http://www.gisimarketing.com/), 17300 S.W. Upper Boones Ferry Road #130

  16. THE JOURNAL OF CHEMICAL PHYSICS 134, 134701 (2011) Binding of hydrogen on benzene, coronene, and graphene from quantum

    E-Print Network [OSTI]

    Alf, Dario

    2011-01-01

    the binding energy curves of hydrogen on benzene, coronene, and graphene. The DMC results on benzene agree well with MP2, giving an adsorption energy of 40 meV. For physisorbed hydrogen on graphene, DMC predicts a very small adsorption energy of only 5 5 meV. Density functional theory (DFT) calculations

  17. Biochem. J. (2002) 362, 265271 (Printed in Great Britain) 265 The transfer of transthyretin and receptor-binding properties from

    E-Print Network [OSTI]

    van Aalten, Daan

    2002-01-01

    SIVAPRASADARAO *School of Biochemistry and Molecular Biology, University of Leeds, Leeds LS2 9JT, U.K., and School of Biomedical Sciences, University of Leeds, Leeds LS2 9JT, U.K. Members of the lipocalin (labelled AH; Figure 1). The interior of the barrel, known as the retinol-binding pocket, is lined

  18. Biochem. J. (2005) 390, 729735 (Printed in Great Britain) doi:10.1042/BJ20050378 729 Phosphorylation of PEA-15 switches its binding specificity from ERK/MAPK

    E-Print Network [OSTI]

    Ramos, Joe W.

    2005-01-01

    Phosphorylation of PEA-15 switches its binding specificity from ERK/MAPK to FADD Hemamalini RENGANATHAN*, Hema the ERK (extracellular-signal-regulated kinase)/MAPK (mitogen- activated protein kinase) pathway and the death receptor-initiated apoptosis pathway. This is the result of PEA-15 binding to the ERK

  19. New Method for Calculating the Absolute Free Energy of Binding: The Effect of a Mobile Loop on the Avidin/Biotin Complex

    E-Print Network [OSTI]

    Meirovitch, Hagai

    New Method for Calculating the Absolute Free Energy of Binding: The Effect of a Mobile Loop energy and entropy. HSMD is extended here for the first time for calculating the absolute free energy change to the total free energy of binding is calculated here for the first time. Our result, A0 ) -24

  20. Stopped-Flow Studies of the Kinetics of Single-Stranded DNA Binding and Wrapping around the Escherichia coli SSB Tetramer

    E-Print Network [OSTI]

    Lohman, Timothy M.

    the Escherichia coli SSB Tetramer Alexander G. Kozlov and Timothy M. Lohman* Department of Biochemistry in which either one molecule of (dT)70 or two molecules of (dT)35 bind per tetramer. Stopped-flow studies. Our results indicate that initial ssDNA binding to the tetramer is very rapid, with a bimolecular rate

  1. The PDZ-binding motif of Yes-associated protein is required for its co-activation of TEAD-mediated CTGF transcription and oncogenic cell transforming activity

    SciTech Connect (OSTI)

    Shimomura, Tadanori; Miyamura, Norio; Hata, Shoji; Miura, Ryota; Hirayama, Jun, E-mail: hirayama.dbio@mri.tmd.ac.jp; Nishina, Hiroshi, E-mail: nishina.dbio@mri.tmd.ac.jp

    2014-01-17

    Highlights: Loss of the PDZ-binding motif inhibits constitutively active YAP (5SA)-induced oncogenic cell transformation. The PDZ-binding motif of YAP promotes its nuclear localization in cultured cells and mouse liver. Loss of the PDZ-binding motif inhibits YAP (5SA)-induced CTGF transcription in cultured cells and mouse liver. -- Abstract: YAP is a transcriptional co-activator that acts downstream of the Hippo signaling pathway and regulates multiple cellular processes, including proliferation. Hippo pathway-dependent phosphorylation of YAP negatively regulates its function. Conversely, attenuation of Hippo-mediated phosphorylation of YAP increases its ability to stimulate proliferation and eventually induces oncogenic transformation. The C-terminus of YAP contains a highly conserved PDZ-binding motif that regulates YAPs functions in multiple ways. However, to date, the importance of the PDZ-binding motif to the oncogenic cell transforming activity of YAP has not been determined. In this study, we disrupted the PDZ-binding motif in the YAP (5SA) protein, in which the sites normally targeted by Hippo pathway-dependent phosphorylation are mutated. We found that loss of the PDZ-binding motif significantly inhibited the oncogenic transformation of cultured cells induced by YAP (5SA). In addition, the increased nuclear localization of YAP (5SA) and its enhanced activation of TEAD-dependent transcription of the cell proliferation gene CTGF were strongly reduced when the PDZ-binding motif was deleted. Similarly, in mouse liver, deletion of the PDZ-binding motif suppressed nuclear localization of YAP (5SA) and YAP (5SA)-induced CTGF expression. Taken together, our results indicate that the PDZ-binding motif of YAP is critical for YAP-mediated oncogenesis, and that this effect is mediated by YAPs co-activation of TEAD-mediated CTGF transcription.

  2. Characterization of a baculovirus lacking the DBP (DNA-binding protein) gene

    SciTech Connect (OSTI)

    Vanarsdall, Adam L. [Department of Microbiology, Nash Hall Room 220, Oregon State University, Corvallis, OR 97331-3804 (United States); Mikhailov, Victor S. [Department of Microbiology, Nash Hall Room 220, Oregon State University, Corvallis, OR 97331-3804 (United States); N.K. Koltzov Institute of Developmental Biology, Russian Academy of Sciences, Moscow 117808 (Russian Federation); Rohrmann, George F. [Department of Microbiology, Nash Hall Room 220, Oregon State University, Corvallis, OR 97331-3804 (United States)]. E-mail: rohrmanng@orst.edu

    2007-08-01

    Autographa californica multiple nucleopolyhedrovirus (AcMNPV) encodes two proteins that possess properties typical of single-stranded DNA-binding proteins (SSBs), late expression factor-3 (LEF-3), and a protein referred to as DNA-binding protein (DBP). Whereas LEF-3 is a multi-functional protein essential for viral DNA replication, transporting helicase into the nucleus, and forms a stable complex with the baculovirus alkaline nuclease, the role for DBP in baculovirus replication remains unclear. Therefore, to better understand the functional role of DBP in viral replication, a DBP knockout virus was generated from an AcMNPV bacmid and analyzed. The results of a growth curve analysis indicated that the dbp knockout construct was unable to produce budded virus indicating that dbp is essential. The lack of DBP does not cause a general shutdown of the expression of viral genes, as was revealed by accumulation of early (LEF-3), late (VP39), and very late (P10) proteins in cells transfected with the dbp knockout construct. To investigate the role of DBP in DNA replication, a real-time PCR-based assay was employed and showed that, although viral DNA synthesis occurred in cells transfected with the dbp knockout, the levels were less than that of the control virus suggesting that DBP is required for normal levels of DNA synthesis or for stability of nascent viral DNA. In addition, analysis of the viral DNA replicated by the dbp knockout by using field inversion gel electrophoresis failed to detect the presence of genome-length DNA. Furthermore, analysis of DBP from infected cells indicated that similar to LEF-3, DBP was tightly bound to viral chromatin. Assessment of the cellular localization of DBP relative to replicated viral DNA by immunoelectron microscopy indicated that, at 24 h post-infection, DBP co-localized with nascent DNA at distinct electron-dense regions within the nucleus. Finally, immunoelectron microscopic analysis of cells transfected with the dbp knockout revealed that DBP is required for the production of normal-appearing nucleocapsids and for the generation of the virogenic stroma.

  3. Binding energy and mechanical stability of single- and multi-walled carbon nanotube serpentines

    SciTech Connect (OSTI)

    Zhao, Junhua, E-mail: junhua.zhao@163.com, E-mail: timon.rabczuk@uni-weimar.de [Jiangsu Key Laboratory of Advanced Food Manufacturing Equipment and Technology, Jiangnan University, 214122 Wuxi (China); Institute of Structural Mechanics, Bauhaus University, 99423 Weimar (Germany); Lu, Lixin [Jiangsu Key Laboratory of Advanced Food Manufacturing Equipment and Technology, Jiangnan University, 214122 Wuxi (China); Rabczuk, Timon, E-mail: junhua.zhao@163.com, E-mail: timon.rabczuk@uni-weimar.de [Institute of Structural Mechanics, Bauhaus University, 99423 Weimar (Germany)

    2014-05-28

    Recently, Geblinger et al. [Nat. Nanotechnol. 3, 195 (2008)] and Machado et al. [Phys. Rev. Lett. 110, 105502 (2013)] reported the experimental and molecular dynamics realization of S-like shaped single-walled carbon nanotubes (CNTs), the so-called CNT serpentines. We reported here results from continuum modeling of the binding energy ? between different single- and multi-walled CNT serpentines and substrates as well as the mechanical stability of the CNT serpentine formation. The critical length for the mechanical stability and adhesion of different CNT serpentines are determined in dependence of E{sub i}I{sub i}, d, and ?, where E{sub i}I{sub i} and d are the CNT bending stiffness and distance of the CNT translation period. Our continuum model is validated by comparing its solution to full-atom molecular dynamics calculations. The derived analytical solutions are of great importance for understanding the interaction mechanism between different single- and multi-walled CNT serpentines and substrates.

  4. Split green fluorescent protein as a modular binding partner for protein crystallization

    SciTech Connect (OSTI)

    Nguyen, Hau B. [Los Alamos National Laboratory, MS M888, Los Alamos, NM 87545 (United States); Hung, Li-Wei [Los Alamos National Laboratory, MS D454, Los Alamos, NM 87545 (United States); Yeates, Todd O. [University of California, PO Box 951569, Los Angeles, CA 90095 (United States); Terwilliger, Thomas C., E-mail: terwilliger@lanl.gov; Waldo, Geoffrey S., E-mail: terwilliger@lanl.gov [Los Alamos National Laboratory, MS M888, Los Alamos, NM 87545 (United States)

    2013-12-01

    A strategy using a new split green fluorescent protein (GFP) as a modular binding partner to form stable protein complexes with a target protein is presented. The modular split GFP may open the way to rapidly creating crystallization variants. A modular strategy for protein crystallization using split green fluorescent protein (GFP) as a crystallization partner is demonstrated. Insertion of a hairpin containing GFP ?-strands 10 and 11 into a surface loop of a target protein provides two chain crossings between the target and the reconstituted GFP compared with the single connection afforded by terminal GFP fusions. This strategy was tested by inserting this hairpin into a loop of another fluorescent protein, sfCherry. The crystal structure of the sfCherry-GFP(1011) hairpin in complex with GFP(19) was determined at a resolution of 2.6 . Analysis of the complex shows that the reconstituted GFP is attached to the target protein (sfCherry) in a structurally ordered way. This work opens the way to rapidly creating crystallization variants by reconstituting a target protein bearing the GFP(1011) hairpin with a variety of GFP(19) mutants engineered for favorable crystallization.

  5. The shape of the DNA minor groove directs binding by the DNA-bending protein Fis

    SciTech Connect (OSTI)

    Stella, Stefano; Cascio, Duilio; Johnson, Reid C.

    2010-06-21

    The bacterial nucleoid-associated protein Fis regulates diverse reactions by bending DNA and through DNA-dependent interactions with other control proteins and enzymes. In addition to dynamic nonspecific binding to DNA, Fis forms stable complexes with DNA segments that share little sequence conservation. Here we report the first crystal structures of Fis bound to high- and low-affinity 27-base-pair DNA sites. These 11 structures reveal that Fis selects targets primarily through indirect recognition mechanisms involving the shape of the minor groove and sequence-dependent induced fits over adjacent major groove interfaces. The DNA shows an overall curvature of {approx}65{sup o}, and the unprecedented close spacing between helix-turn-helix motifs present in the apodimer is accommodated by severe compression of the central minor groove. In silico DNA structure models show that only the roll, twist, and slide parameters are sufficient to reproduce the changes in minor groove widths and recreate the curved Fis-bound DNA structure. Models based on naked DNA structures suggest that Fis initially selects DNA targets with intrinsically narrow minor grooves using the separation between helix-turn-helix motifs in the Fis dimer as a ruler. Then Fis further compresses the minor groove and bends the DNA to generate the bound structure.

  6. cAMP-response-element-binding protein positively regulates breast cancer metastasis and subsequent bone destruction

    SciTech Connect (OSTI)

    Son, Jieun; Lee, Jong-Ho; Kim, Ha-Neui; Ha, Hyunil Lee, Zang Hee

    2010-07-23

    Research highlights: {yields} CREB is highly expressed in advanced breast cancer cells. {yields} Tumor-related factors such as TGF-{beta} further elevate CREB expression. {yields} CREB upregulation stimulates metastatic potential of breast cancer cells. {yields} CREB signaling is required for breast cancer-induced bone destruction. -- Abstract: cAMP-response-element-binding protein (CREB) signaling has been reported to be associated with cancer development and poor clinical outcome in various types of cancer. However, it remains to be elucidated whether CREB is involved in breast cancer development and osteotropism. Here, we found that metastatic MDA-MB-231 breast cancer cells exhibited higher CREB expression than did non-metastatic MCF-7 cells and that CREB expression was further increased by several soluble factors linked to cancer progression, such as IL-1, IGF-1, and TGF-{beta}. Using wild-type CREB and a dominant-negative form (K-CREB), we found that CREB signaling positively regulated the proliferation, migration, and invasion of MDA-MB-231 cells. In addition, K-CREB prevented MDA-MB-231 cell-induced osteolytic lesions in a mouse model of cancer metastasis. Furthermore, CREB signaling in cancer cells regulated the gene expression of PTHrP, MMPs, and OPG, which are closely involved in cancer metastasis and bone destruction. These results indicate that breast cancer cells acquire CREB overexpression during their development and that this CREB upregulation plays an important role in multiple steps of breast cancer bone metastasis.

  7. Coordination-resolved local bond contraction and electron binding-energy entrapment of Si atomic clusters and solid skins

    SciTech Connect (OSTI)

    Bo, Maolin; Huang, Yongli; Zhang, Ting [Key Laboratory of Low-Dimensional Materials and Application Technologies, Xiangtan University, Hunan 411105 (China); Wang, Yan, E-mail: ywang8@hnust.edu.cn, E-mail: ecqsun@ntu.edu.sg [Key Laboratory of Low-Dimensional Materials and Application Technologies, Xiangtan University, Hunan 411105 (China); School of Information and Electronic Engineering, Hunan University of Science and Technology, Hunan 411201 (China); Zhang, Xi [School of Electrical and Electronic Engineering, Nanyang Technological University, Singapore 639798 (Singapore); Li, Can [Center for Coordination Bond Engineering, School of Materials Science and Engineering, China Jiliang University, Hangzhou 330018 (China); Sun, Chang Q., E-mail: ywang8@hnust.edu.cn, E-mail: ecqsun@ntu.edu.sg [Key Laboratory of Low-Dimensional Materials and Application Technologies, Xiangtan University, Hunan 411105 (China); School of Electrical and Electronic Engineering, Nanyang Technological University, Singapore 639798 (Singapore); Center for Coordination Bond Engineering, School of Materials Science and Engineering, China Jiliang University, Hangzhou 330018 (China)

    2014-04-14

    Consistency between x-ray photoelectron spectroscopy measurements and density-function theory calculations confirms our bond order-length-strength notation-incorporated tight-binding theory predictions on the quantum entrapment of Si solid skin and atomic clusters. It has been revealed that bond-order deficiency shortens and strengthens the Si-Si bond, which results in the local densification and quantum entrapment of the core and valence electrons. Unifying Si clusters and Si(001) and (111) skins, this mechanism has led to quantification of the 2p binding energy of 96.089?eV for an isolated Si atom, and their bulk shifts of 2.461?eV. Findings evidence the significance of atomic undercoordination that is of great importance to device performance.

  8. Quantification of the epitope diversity of HIV-1-specific binding antibodies by peptide microarrays for global HIV-1 vaccine development

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Stephenson, Kathryn E.; Neubauer, George H.; Reimer, Ulf; Pawlowski, Nikolaus; Knaute, Tobias; Zerweck, Johannes; Korber, Bette T.; Barouch, Dan H.

    2014-11-14

    An effective vaccine against human immunodeficiency virus type 1 (HIV-1) will have to provide protection against a vast array of different HIV-1 strains. Current methods to measure HIV-1-specific binding antibodies following immunization typically focus on determining the magnitude of antibody responses, but the epitope diversity of antibody responses has remained largely unexplored. Here we describe the development of a global HIV-1 peptide microarray that contains 6564 peptides from across the HIV-1 proteome and covers the majority of HIV-1 sequences in the Los Alamos National Laboratory global HIV-1 sequence database. Using this microarray, we quantified the magnitude, breadth, and depth ofmoreIgG binding to linear HIV-1 sequences in HIV-1-infected humans and HIV-1-vaccinated humans, rhesus monkeys and guinea pigs. The microarray measured potentially important differences in antibody epitope diversity, particularly regarding the depth of epitope variants recognized at each binding site. Our data suggest that the global HIV-1 peptide microarray may be a useful tool for both preclinical and clinical HIV-1 research.less

  9. Subfamily-specific adaptations in the structures of two penicillin-binding proteins from Mycobacterium tuberculosis

    SciTech Connect (OSTI)

    Prigozhin, Daniil M. [Univ. of California, Berkeley, CA (United States); Krieger, Inna V. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Texas A & M Univ., College Station, TX (United States); Huizar, John P. [Univ. of California, Berkeley, CA (United States); Mavrici, Daniela [Univ. of California, Berkeley, CA (United States); Waldo, Geoffrey S. [Univ. of California, Berkeley, CA (United States); Hung, Li -Wei [Univ. of California, Berkeley, CA (United States); Sacchettini, James C. [Texas A & M Univ., College Station, TX (United States); Terwilliger, Thomas C. [Univ. of California, Berkeley, CA (United States); Alber, Tom [Univ. of California, Berkeley, CA (United States); Mayer, Claudine [Institut Pasteur, Paris (France)

    2014-12-31

    Beta-lactam antibiotics target penicillin-binding proteins including several enzyme classes essential for bacterial cell-wall homeostasis. To better understand the functional and inhibitor-binding specificities of penicillin-binding proteins from the pathogen, Mycobacterium tuberculosis, we carried out structural and phylogenetic analysis of two predicted D,D-carboxypeptidases, Rv2911 and Rv3330. Optimization of Rv2911 for crystallization using directed evolution and the GFP folding reporter method yielded a soluble quadruple mutant. Structures of optimized Rv2911 bound to phenylmethylsulfonyl fluoride and Rv3330 bound to meropenem show that, in contrast to the nonspecific inhibitor, meropenem forms an extended interaction with the enzyme along a conserved surface. Phylogenetic analysis shows that Rv2911 and Rv3330 belong to different clades that emerged in Actinobacteria and are not represented in model organisms such as Escherichia coli and Bacillus subtilis. Clade-specific adaptations allow these enzymes to fulfill distinct physiological roles despite strict conservation of core catalytic residues. The characteristic differences include potential protein-protein interaction surfaces and specificity-determining residues surrounding the catalytic site. Overall, these structural insights lay the groundwork to develop improved beta-lactam therapeutics for tuberculosis.

  10. Electronic Structures, Bonding Configurations, and Band-Gap-Opening Properties of Graphene Binding with Low-Concentration Fluorine

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Duan, Yuhua; Stinespring, Charter D.; Chorpening, Benjamin

    2015-06-18

    To better understand the effects of low-level fluorine in graphene-based sensors, first-principles density functional theory (DFT) with van der Waals dispersion interactions has been employed to investigate the structure and impact of fluorine defects on the electrical properties of single-layer graphene films. The results show that both graphite-2H and graphene have zero band gaps. When fluorine bonds to a carbon atom, the carbon atom is pulled slightly above the graphene plane, creating what is referred to as a CF defect. The lowest-binding energy state is found to correspond to two CF defects on nearest neighbor sites, with one fluorine abovemorethe carbon plane and the other below the plane. Overall this has the effect of buckling the graphene. The results further show that the addition of fluorine to graphene leads to the formation of an energy band (BF) near the Fermi level, contributed mainly from the 2p orbitals of fluorine with a small contribution from the porbitals of the carbon. Among the 11 binding configurations studied, our results show that only in two cases does the BF serve as a conduction band and open a band gap of 0.37 eV and 0.24 eV respectively. The binding energy decreases with decreasing fluorine concentration due to the interaction between neighboring fluorine atoms. The obtained results are useful for sensor development and nanoelectronics.less

  11. Design of Bcl-2 and Bcl-xL Inhibitors with Subnanomolar Binding Affinities Based upon a New Scaffold

    SciTech Connect (OSTI)

    Zhou, Haibin; Chen, Jianfang; Meagher, Jennifer L.; Yang, Chao-Yie; Aguilar, Angelo; Liu, Liu; Bai, Longchuan; Cong, Xin; Cai, Qian; Fang, Xueliang; Stuckey, Jeanne A.; Wang, Shaomeng

    2014-10-02

    Employing a structure-based strategy, we have designed a new class of potent small-molecule inhibitors of the anti-apoptotic proteins Bcl-2 and Bcl-xL. An initial lead compound with a new scaffold was designed based upon the crystal structure of Bcl-xL and U.S. Food and Drug Administration (FDA) approved drugs and was found to have an affinity of 100 {micro}M for both Bcl-2 and Bcl-xL. Linking this weak lead to another weak-affinity fragment derived from Abbott's ABT-737 led to an improvement of the binding affinity by a factor of >10,000. Further optimization ultimately yielded compounds with subnanomolar binding affinities for both Bcl-2 and Bcl-xL and potent cellular activity. The best compound (21) binds to Bcl-xL and Bcl-2 with K{sub i} < 1 nM, inhibits cell growth in the H146 and H1417 small-cell lung cancer cell lines with IC{sub 50} values of 60-90 nM, and induces robust cell death in the H146 cancer cell line at 30-100 nM.

  12. Numerical calculation of protein-ligand binding rates through solution of the Smoluchowski equation using smoothed particle hydrodynamics

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Pan, Wenxiao; Daily, Michael; Baker, Nathan A.

    2015-05-07

    Background: The calculation of diffusion-controlled ligand binding rates is important for understanding enzyme mechanisms as well as designing enzyme inhibitors. Methods: We demonstrate the accuracy and effectiveness of a Lagrangian particle-based method, smoothed particle hydrodynamics (SPH), to study diffusion in biomolecular systems by numerically solving the time-dependent Smoluchowski equation for continuum diffusion. Unlike previous studies, a reactive Robin boundary condition (BC), rather than the absolute absorbing (Dirichlet) BC, is considered on the reactive boundaries. This new BC treatment allows for the analysis of enzymes with imperfect reaction rates. Results: The numerical method is first verified in simple systems and thenmoreapplied to the calculation of ligand binding to a mouse acetylcholinesterase (mAChE) monomer. Rates for inhibitor binding to mAChE are calculated at various ionic strengths and compared with experiment and other numerical methods. We find that imposition of the Robin BC improves agreement between calculated and experimental reaction rates. Conclusions: Although this initial application focuses on a single monomer system, our new method provides a framework to explore broader applications of SPH in larger-scale biomolecular complexes by taking advantage of its Lagrangian particle-based nature.less

  13. Evaluation of polyacrylonitrile (PAN) as a binding polymer for absorbers used to treat liquid radioactive wastes

    SciTech Connect (OSTI)

    Sebesta, F.; John, J.; Motl, A.; Stamberg, K.

    1995-11-01

    The chemical and radiation stability of polyacrylonitrile (PAN) in the form of beads (B-PAN), similar to the beads of composite absorbers, and one selected composite absorber (ammonium molybdophosphate, the active component in PAN binder [AMP-PAN], a prospective candidate for the treatment of acidic wastes) were studied. Aqueous 1M HNO{sub 3} + 1M NaNO{sub 3}, 1M NaOH + 1M NaNO{sub 3}, and 1M NaOH were chosen as simulants of DOE acidic and alkaline wastes. In addition,radiation stability was determined indistilled water. The chemical stability of B-PAN and AMP-PAN beads was tested for a period up to one month of contact with the solution at ambient temperature. The radiation stability of the beads was checked in a radiation dose range 10{sup 3}--10{sup 6} Gy (10{sup 5}--10{sup 8} rads). In acidic solutions the stability of PAN binder was proved not to be limited by either chemical or radiation decomposition. PAN binder may thus be used for preparing composite absorbers for treatment of acid wastes from DOE facilities. The same conclusion is valid for alkaline solutions with pH up to 13. In highly alkaline solutions (concentration of NAOH higher than I M) and in the presence of NaNO{sub 3}, the stability of the tested polyacrylonitrile polymer was sufficient for applications not extending over 10 days. Cross-linking of the polymer caused by ionizing radiation was found to have a positive influence on chemical stability. This effect enables a longer period of applicability of PAN-based composite absorbers. Because of the high sorption rate achievable with PAN-based absorbers, the stability achieved is sufficient for most applications in the DOE complex. The chemical stability of binding polymer may also be further improved by testing another, more suitable type of polymer from the broad family of polyacrylonitrile polymers.

  14. Anion Binding in Metal-Organic Frameworks Functionalized with Urea Hydrogen-Bonding Groups

    SciTech Connect (OSTI)

    Custelcean, Radu; Moyer, Bruce A; Bryantsev, Vyacheslav S.; Hay, Benjamin P.

    2006-01-01

    A series of metal-organic frameworks (MOFs) functionalized with urea hydrogen-bonding groups has been synthesized and structurally analyzed by single-crystal X-ray diffraction to evaluate the efficacy of anion coordination by urea within the structural constraints of the MOFs. We found that urea-based functionalities may be used for anion binding within metal-organic frameworks when the tendency for urea{hor_ellipsis}urea self-association is decreased by strengthening the intramolecular CH{hor_ellipsis}O hydrogen bonding of N-phenyl substituents to the carbonyl oxygen atom. Theoretical calculations indicate that N,N'-bis(m-pyridyl)urea (BPU) and N,N'-bis(m-cyanophenyl)urea (BCPU) should have enhanced hydrogen-bonding donor abilities toward anions and decreased tendencies to self-associate into hydrogen-bonded tapes compared to other disubstituted ureas. Accordingly, BPU and BCPU were incorporated in MOFs as linkers through coordination of various Zn, Cu, and Ag transition metal salts, including Zn(ClO{sub 4}){sub 2}, ZnSO{sub 4}, Cu(NO{sub 3}){sub 2}, Cu(CF{sub 3}SO{sub 3}){sub 2}, AgNO{sub 3}, and AgSO{sub 3}CH{sub 3}. Structural analysis by single-crystal X-ray diffraction showed that these linkers are versatile anion binders, capable of chelate hydrogen bonding to all of the oxoanions explored. Anion coordination by the urea functionalities was found to successfully compete with urea self-association in all cases except for that of charge-diffuse perchlorate.

  15. Apoferritin-based nanomedicine platform for drug delivery: equilibrium binding study of daunomycin with DNA

    SciTech Connect (OSTI)

    Ma Ham, Aihui; Wu, Hong J.; Wang, Jun; Kang, Xinhuang; Zhang, Youyu; Lin, Yuehe

    2011-05-11

    Apoferritin is a nanostructured material with a uniform size and spherical structure, and it has excellent bio-compatibility. In this work, we report the use of apoferritin as a novel and biocompatible carrier for stabilizing enzymes and their activities. We used glucose oxidase (GOx) as a model enzyme. GOx was immobilized on the surface of the apoferritin through a green synthetic approach taking advantage of bioaffinity binding between streptavidin and biotin. As a result, a glucose oxidase-biotin/streptavidin/biotin-apoferritin conjugate (Apo-GOx) was prepared using streptavidin as a bridge. The synthesized Apo-GOx was characterized with transmission electron microscopy, ultraviolet, and fluorescence spectroscopy. The activity and stability of GOx on the surface of the apoferritin were studied in different environments, such as temperature, chemicals, and pH, in comparison with the biotinylated GOx (B-GOx). The results showed that the activity of GOx on the apoferritin surface was significantly enhanced. The thermal and chemical stability of the GOx on the apoferritin was also greatly improved compared to free B-GOx in a solution. It was found that the activity of the GOx on the apoferritin only lost 30% in comparison to a 70% loss of free B-GOx after a 2-hr incubation at 50oC. There was almost no decrease in activity for the GOx on the apoferritin as compared to an 80% activity decrease for free B-GOx after 30 minutes of incubation in a 5 M urea solution. The GOx immobilized apoferritin nanoparticles exhibited high sensitivity for glucose detection with a detection limit of 3 nM glucose. This work offers a novel approach for immobilizing enzymes with enhanced stability and activity, and this method may find a number of applications, such as in catalysis and bioassys/biosensors.

  16. Inhibition of Amyloid-? (A?) Peptide-Binding Alcohol Dehydrogenase-A? Interaction Reduces A? Accumulation and Improves Mitochondrial Function in a Mouse Model of Alzheimer's Disease

    E-Print Network [OSTI]

    Yao, Jun; Du, Heng; Yan, Shiqiang; Fang, Fang; Wang, Chaodong; Lue, Lih-Fen; Guo, Lan; Chen, Doris; Stern, David M.; Moore, Frank J. Gunn; Chen, John Xi; Arancio, Ottavio; Yan, Shirley ShiDu

    2011-02-09

    Amyloid-? (A?) peptide-binding alcohol dehydrogenase (ABAD), an enzyme present in neuronal mitochondria, exacerbates A?-induced cell stress. The interaction of ABAD with A? exacerbates A?-induced mitochondrial and neuronal ...

  17. A novel RUNX2 missense mutation predicted to disrupt DNA binding causes cleidocranial dysplasia in a large Chinese family with hyperplastic nails

    E-Print Network [OSTI]

    2007-01-01

    to disrupt DNA binding causes cleidocranial dysplasia in awhich traces (p.L136P) causes showing a change the missensemutation in c.T407C, which causes a change from leucine to

  18. The structure of SecB/OmpA as visualized by electron microscopy: The mature region of the precursor protein binds asymmetrically to SecB

    SciTech Connect (OSTI)

    Tang, Ying; Pan, Xijiang [State-Key Laboratory of Biomembrane and Membrane Biotechnology, Center for Structural Biology, School of Life Science, Tsinghua University, Beijing 100084 (China)] [State-Key Laboratory of Biomembrane and Membrane Biotechnology, Center for Structural Biology, School of Life Science, Tsinghua University, Beijing 100084 (China); Tai, Phang C. [Department of Biology, Georgia State University, Atlanta, GA 30303 (United States)] [Department of Biology, Georgia State University, Atlanta, GA 30303 (United States); Sui, Sen-Fang, E-mail: suisf@mail.tsinghua.edu.cn [State-Key Laboratory of Biomembrane and Membrane Biotechnology, Center for Structural Biology, School of Life Science, Tsinghua University, Beijing 100084 (China)] [State-Key Laboratory of Biomembrane and Membrane Biotechnology, Center for Structural Biology, School of Life Science, Tsinghua University, Beijing 100084 (China)

    2010-03-19

    SecB, a molecular chaperone in Escherichia coli, binds a subset of precursor proteins that are exported across the plasma membrane via the Sec pathway. Previous studies showed that SecB bound directly to the mature region rather than to the signal sequence of the precursor protein. To determine the binding pattern of SecB and the mature region of the preprotein, here, we visualized the structure of the SecB/OmpA complex by electron microscopy. This complex is composed by two parts: the main density represents one SecB tetramer and the unfolded part of OmpA wrapping round it; the elongated smaller density represents the rest of OmpA. Each SecB protomer makes a different contribution to the binding of SecB with OmpA. The binding pattern between SecB tetramer and OmpA is asymmetric.

  19. Insights on the binding of thioflavin derivative markers to amyloid fibril models and A?{sub 1-40} fibrils from computational approaches

    SciTech Connect (OSTI)

    Al-Torres, Jorge; Rimola, Albert; Sodupe, Mariona; Rodriguez-Rodrguez, Cristina

    2014-10-06

    The present contribution analyzes the binding of ThT and neutral ThT derivatives to a ?-sheet model by means of quantum chemical calculations. In addition, we study the properties of four molecules: (2-(2-hydroxyphenyl)benzoxazole (HBX), 2-(2-hydroxyphenyl)benzothiazole (HBT) and their respective iodinated compounds, HBXI and HBTI, in binding to amyloid fibril models and A?{sub 1-40}fibrils by using a combination of docking, molecular dynamics and quantum mechanics calculations.

  20. Kinetic and equilibrium studies of acrylonitrile binding to cytochrome c peroxidase and oxidation of acrylonitrile by cytochrome c peroxidase compound I

    SciTech Connect (OSTI)

    Chinchilla, Diana, E-mail: Diana_Chinchilla@yahoo.com; Kilheeney, Heather, E-mail: raindropszoo@yahoo.com; Vitello, Lidia B., E-mail: lvitello@niu.edu; Erman, James E., E-mail: jerman@niu.edu

    2014-01-03

    Highlights: Cytochrome c peroxidase (CcP) binds acrylonitrile in a pH-independent fashion. The spectrum of the CcP/acrylonitrile complex is that of a 6cls ferric heme. The acrylonitrile/CcP complex has a K{sub D} value of 1.1 0.2 M. CcP compound I oxidizes acrylonitrile with a maximum turnover rate of 0.61 min{sup ?1}. -- Abstract: Ferric heme proteins bind weakly basic ligands and the binding affinity is often pH dependent due to protonation of the ligand as well as the protein. In an effort to find a small, neutral ligand without significant acid/base properties to probe ligand binding reactions in ferric heme proteins we were led to consider the organonitriles. Although organonitriles are known to bind to transition metals, we have been unable to find any prior studies of nitrile binding to heme proteins. In this communication we report on the equilibrium and kinetic properties of acrylonitrile binding to cytochrome c peroxidase (CcP) as well as the oxidation of acrylonitrile by CcP compound I. Acrylonitrile binding to CcP is independent of pH between pH 4 and 8. The association and dissociation rate constants are 0.32 0.16 M{sup ?1} s{sup ?1} and 0.34 0.15 s{sup ?1}, respectively, and the independently measured equilibrium dissociation constant for the complex is 1.1 0.2 M. We have demonstrated for the first time that acrylonitrile can bind to a ferric heme protein. The binding mechanism appears to be a simple, one-step association of the ligand with the heme iron. We have also demonstrated that CcP can catalyze the oxidation of acrylonitrile, most likely to 2-cyanoethylene oxide in a peroxygenase-type reaction, with rates that are similar to rat liver microsomal cytochrome P450-catalyzed oxidation of acrylonitrile in the monooxygenase reaction. CcP compound I oxidizes acrylonitrile with a maximum turnover number of 0.61 min{sup ?1} at pH 6.0.

  1. Near-infrared fluorescence glucose sensing based on glucose/galactose-binding protein coupled to 651-Blue Oxazine

    SciTech Connect (OSTI)

    Khan, Faaizah; Pickup, John C.

    2013-08-30

    Highlights: We showed that the NIR fluorophore, 651-Blue Oxazine, is solvatochromic (polarity sensitive). Blue Oxazine was covalently attached to mutants of glucose/galactose-binding protein (GBP). Fluorescence intensity of GBP-Blue Oxazine increased with addition of glucose. Fluorescence from bead-immobilised GBP-Blue Oxazine was detectable through skin in vitro. This shows proof-of-concept for non-invasive glucose sensing using GBP-Blue Oxazine. -- Abstract: Near-infrared (NIR) fluorescent dyes that are environmentally sensitive or solvatochromic are useful tools for protein labelling in in vivo biosensor applications such as glucose monitoring in diabetes since their spectral properties are mostly independent of tissue autofluorescence and light scattering, and they offer potential for non-invasive analyte sensing. We showed that the fluorophore 651-Blue Oxazine is polarity-sensitive, with a marked reduction in NIR fluorescence on increasing solvent polarity. Mutants of glucose/galactose-binding protein (GBP) used as the glucose receptor were site-specifically and covalently labelled with Blue Oxazine using click chemistry. Mutants H152C/A213R and H152C/A213R/L238S showed fluorescence increases of 15% and 21% on addition of saturating glucose concentrations and binding constants of 6 and 25 mM respectively. Fluorescence responses to glucose were preserved when GBP-Blue Oxazine was immobilised to agarose beads, and the beads were excited by NIR light through a mouse skin preparation studied in vitro. We conclude GBP-Blue Oxazine shows proof-of-concept as a non-invasive continuous glucose sensing system.

  2. Binding energies and spatial structures of small carrier complexes in monolayer transition-metal dichalcogenides via diffusion Monte Carlo

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Mayers, Matthew Z.; Berkelbach, Timothy C.; Hybertsen, Mark S.; Reichman, David R.

    2015-10-09

    Ground-state diffusion Monte Carlo is used to investigate the binding energies and intercarrier radial probability distributions of excitons, trions, and biexcitons in a variety of two-dimensional transition-metal dichalcogenide materials. We compare these results to approximate variational calculations, as well as to analogous Monte Carlo calculations performed with simplified carrier interaction potentials. Our results highlight the successes and failures of approximate approaches as well as the physical features that determine the stability of small carrier complexes in monolayer transition-metal dichalcogenide materials. In conclusion, we discuss points of agreement and disagreement with recent experiments.

  3. The role of amino acid electron-donor/acceptor atoms in host-cell binding peptides is associated with their 3D structure and HLA-binding capacity in sterile malarial immunity induction

    SciTech Connect (OSTI)

    Patarroyo, Manuel E.; Almonacid, Hannia; Moreno-Vranich, Armando

    2012-01-20

    Highlights: Black-Right-Pointing-Pointer Fundamental residues located in some HABPs are associated with their 3D structure. Black-Right-Pointing-Pointer Electron-donor atoms present in {beta}-turn, random, distorted {alpha}-helix structures. Black-Right-Pointing-Pointer Electron-donor atoms bound to HLA-DR53. Black-Right-Pointing-Pointer Electron-acceptor atoms present in regular {alpha}-helix structure bound to HLA-DR52. -- Abstract: Plasmodium falciparum malaria continues being one of the parasitic diseases causing the highest worldwide mortality due to the parasite's multiple evasion mechanisms, such as immunological silence. Membrane and organelle proteins are used during invasion for interactions mediated by high binding ability peptides (HABPs); these have amino acids which establish hydrogen bonds between them in some of their critical binding residues. Immunisation assays in the Aotus model using HABPs whose critical residues had been modified have revealed a conformational change thereby enabling a protection-inducing response. This has improved fitting within HLA-DR{beta}1{sup Asterisk-Operator} molecules where amino acid electron-donor atoms present in {beta}-turn, random or distorted {alpha}-helix structures preferentially bound to HLA-DR53 molecules, whilst HABPs having amino acid electron-acceptor atoms present in regular {alpha}-helix structure bound to HLA-DR52. This data has great implications for vaccine development.

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  5. The protein tyrosine phosphatases PTPRZ and PTPRG bind to distinct members of the contactin family of neural recognition molecules

    SciTech Connect (OSTI)

    Bouyain, Samuel; Watkins, Dara J. (UMKC)

    2010-04-05

    The receptor protein tyrosine phosphatases gamma (PTPRG) and zeta (PTPRZ) are expressed primarily in the nervous system and mediate cell adhesion and signaling events during development. We report here the crystal structures of the carbonic anhydrase-like domains of PTPRZ and PTPRG and show that these domains interact directly with the second and third immunoglobulin repeats of the members of the contactin (CNTN) family of neural recognition molecules. Interestingly, these receptors exhibit distinct specificities: PTPRZ binds only to CNTN1, whereas PTPRG interacts with CNTN3, 4, 5, and 6. Furthermore, we present crystal structures of the four N-terminal immunoglobulin repeats of mouse CNTN4 both alone and in complex with the carbonic anhydrase-like domain of mouse PTPRG. In these structures, the N-terminal region of CNTN4 adopts a horseshoe-like conformation found also in CNTN2 and most likely in all CNTNs. This restrained conformation of the second and third immunoglobulin domains creates a binding site that is conserved among CNTN3, 4, 5, and 6. This site contacts a discrete region of PTPRG composed primarily of an extended {beta}-hairpin loop found in both PTPRG and PTPRZ. Overall, these findings implicate PTPRG, PTPRZ and CNTNs as a group of receptors and ligands involved in the manifold recognition events that underlie the construction of neural networks.

  6. Non-binding conductor load bearing roller for a gas-insulated transmission line having a corrugated outer conductor

    DOE Patents [OSTI]

    Fischer, William H. (Pittsburgh, PA)

    1984-01-01

    A gas-insulated transmission line includes a corrugated outer conductor, an inner conductor disposed within and insulated from the outer conductor by means of support insulators and an insulating gas, and a non-binding transport device for supporting and permitting movement of the inner conductor/insulating support assembly axially along the corrugated outer conductor without radial displacement and for moving without binding along corrugations of any slope less than vertical. The transport device includes two movable contacts, such as skids or rollers, supported on a common pivot lever, the pivot lever being rotatably disposed about a pivot lever axis, which pivot lever axis is in turn disposed on the periphery of a support insulator or particle trap if one is used. The movable contacts are separated axially a distance equal to the axial distance between the peaks and valleys of the corrugations of the outer conductor and separated radially a distance equal to the radial distance between the peaks and valleys of the corrugations of the outer conductor. The transport device has the pivot lever axis disposed parallel to the motion of travel of the inner conductor/insulating support assembly.

  7. Modeling the Interaction between Integrin-Binding Peptide (RGD) and Rutile Surface: The Effect of Na+ on Peptide Adsorption

    SciTech Connect (OSTI)

    Wu, Chunya; Skelton, Adam; Chen, Mingjun; Vlcek, Lukas; Cummings, Peter T

    2011-01-01

    The dynamics of a single tripeptide Arg-Gly-Asp (RGD) adsorbing onto negatively charged hydroxylated rutile (110) surface in aqueous solution was studied using molecular dynamics (MD) simulations. The results indicate that the adsorbed Na{sup +} ions play an important role in determining the binding geometry of RGD. With an initial 'horseshoe' configuration, the charged side groups (COO{sup -} and NH{sub 2}) of the peptide are able to interact with the surface through direct hydrogen bonds (H bonds) in the very early stage of adsorption. The Na{sup +} ions approach the positively charged Arg side chain, competing with the Arg side chain for adsorption to the negatively charged hydroxyl oxygen. In coordination with the structural adjustment of the peptide, the Arg residue is driven to detach from the rutile surface. In contrast, the Na+ ions in close proximity to the negatively charged Asp side chain contribute to the binding of the COO{sup -} group on the surface, helping the carboxyl oxygen not involved in COO{sup -}-surface H bonds to orientate toward the hydroxyl hydrogens. Once both carboxyl oxygens form enough H bonds with the hydroxyl hydrogens, the redundant ions move toward a more favorable adsorption site.

  8. Functional glass slides for in vitro evaluation of interactions between osteosarcoma TE85 cells and mineral-binding ligands

    SciTech Connect (OSTI)

    Song, Jie; Chen, Julia; Klapperich, Catherine M.; Eng, Vincent; Bertozzi, Carolyn R.

    2004-07-20

    Primary amine-functionalized glass slides obtained through a multi-step plasma treatment were conjugated with anionic amino acids that are frequently found as mineral binding elements in acidic extracellular matrix components of natural bone. The modified glass surfaces were characterized by X-ray photoelectron spectroscopy (XPS) and contact angle measurements. Human osteosarcoma TE85 cells were cultured on these functionalized slides and analyses on both protein and gene expression levels were performed to probe the ''biocompatibility'' of the surface ligands. Cell attachment and proliferation on anionic surfaces were either better than or comparable to those of cells cultured on tissue culture polystyrene (TCPS). The modified glass surfaces promoted the expression of osteocalcin, alkaline phosphatase activity and ECM proteins such as fibronectin and vitronectin under differentiation culture conditions. Transcript analysis using gene chip microarrays confirmed that culturing TE85 cells on anionic surfaces did not activate apoptotic pathways. Collectively, these results suggest that the potential mineral-binding anionic ligands examined here do not exert significant adverse effects on the expression of important osteogenic markers of TE85 cells. This work paves the way for the incorporation of these ligands into 3-dimensional artificial bone-like scaffolds.

  9. Structure-Based Design of Robust Glucose Biosensors using a Thermotoga maritima Periplasmic Glucose-Binding Protein

    SciTech Connect (OSTI)

    Tian,Y.; Cunco, M.; Changela, A.; Hocker, B.; Beese, L.; Hellinga, H.

    2007-01-01

    We report the design and engineering of a robust, reagentless fluorescent glucose biosensor based on the periplasmic glucose-binding protein obtained from Thermotoga maritima (tmGBP). The gene for this protein was cloned from genomic DNA and overexpressed in Escherichia coli, the identity of its cognate sugar was confirmed, ligand binding was studied, and the structure of its glucose complex was solved to 1.7 Angstroms resolution by X-ray crystallography. TmGBP is specific for glucose and exhibits high thermostability (midpoint of thermal denaturation is 119 {+-} 1 C and 144 {+-} 2 C in the absence and presence of 1 mM glucose, respectively). A series of fluorescent conjugates was constructed by coupling single, environmentally sensitive fluorophores to unique cysteines introduced by site-specific mutagenesis at positions predicted to be responsive to ligand-induced conformational changes based on the structure. These conjugates were screened to identify engineered tmGBPs that function as reagentless fluorescent glucose biosensors. The Y13C Cy5 conjugate is bright, gives a large response to glucose over concentration ranges appropriate for in vivo monitoring of blood glucose levels (1-30 mM), and can be immobilized in an orientation-specific manner in microtiter plates to give a reversible response to glucose. The immobilized protein retains its response after long-term storage at room temperature.

  10. H2-M polymorphism in mice susceptible to collagen-induced arthritis involves the peptide binding groove

    SciTech Connect (OSTI)

    Walter, W.; Loos, M.; Maeurer, M.J.

    1996-12-31

    The ability to develop type II collagen (CII)-induced arthritis (CIA) in mice is associated with the major histocompatibility I-A gene and with as yet poorly defined regulatory molecules of the major histocompatibility complex (MHC) class II antigen processing and presentation pathway. H2-M molecules are thought to be involved in the loading of antigenic peptides into the MHC class II binding cleft. We sequenced H2-Ma, H2-Mb1, and H2-Mb2 genes from CIA-susceptible and -resistant mouse strains and identified four different Ma and Mb2 alleles, and three different Mb1 alleles defined by polymorphic residues within the predicted peptide binding groove. Most CIA-resistant mouse strains share common Ma, Mb1, and Mb2 alleles. In contrast, H2-M alleles designated Ma-III, Ma-IV, Mb1-III, and Mb2-IV could be exclusively identified in the CIA-susceptible H2{sup r} and H2{sup q} haplotypes, suggesting that allelic H2-M molecules may modulate the composition of different CII peptides loaded onto MHC class II molecules, presumably presenting {open_quotes}arthritogenic{close_quotes} epitopes to T lymphocytes. 42 refs., 4 figs., 3 tabs.

  11. The Influence of Spatial Variation in Chromatin Density Determined by X-ray Tomograms on the Time to Find DNA Binding Sites

    E-Print Network [OSTI]

    Samuel A. Isaacson; Carolyn A. Larabell; Mark A. Le Gros; David M. McQueen; Charles S. Peskin

    2013-08-19

    In this work we examine how volume exclusion caused by regions of high chromatin density might influence the time required for proteins to find specific DNA binding sites. The spatial variation of chromatin density within mouse olfactory sensory neurons is determined from soft X-ray tomography reconstructions of five nuclei. We show that there is a division of the nuclear space into regions of low-density euchromatin and high-density heterochromatin. Volume exclusion experienced by a diffusing protein caused by this varying density of chromatin is modeled by a repulsive potential. The value of the potential at a given point in space is chosen to be proportional to the density of chromatin at that location. The constant of proportionality, called the volume exclusivity, provides a model parameter that determines the strength of volume exclusion. Numerical simulations demonstrate that the mean time for a protein to locate a binding site localized in euchromatin is minimized for a finite, non-zero volume exclusivity. For binding sites in heterochromatin, the mean time is minimized when the volume exclusivity is zero (the protein experiences no volume exclusion). An analytical theory is developed to explain these results. The theory suggests that for binding sites in euchromatin there is an optimal level of volume exclusivity that balances a reduction in the volume searched in finding the binding site, with the height of effective potential barriers the protein must cross during the search process.

  12. Negative Electron Binding Energies Observed in a Triply Charged Anion: Photoelectron Spectroscopy of 1-Hydroxy-3, 6, 8-Pyrene-Trisulfonate

    SciTech Connect (OSTI)

    Yang, Jie; Xing, Xiaopeng; Wang, Xue B.; Wang, Lai S.; Sergeeva, Alina P.; Boldyrev, Alexander I.

    2008-03-07

    We report the observation of negative electron binding energies in a triply charged anion, 1-hydroxy-3,6,8-pyrene-trisulfonate (HPTS3). Low-temperature photoelectron spectra were obtained for HPTS3 at several photon energies, revealing three detachment features below 0 electron binding energy. The HPTS3 trianion was measured to possess a negative electron binding of -0.66 eV. Despite the relatively high excess energy stored in HPTS3, it was observed to be a long-lived anion due to its high repulsive Coulomb barrier (~3.3 eV), which prevents spontaneous electron emission. Theoretical calculations were carried out, which confirmed the negative electron binding energies observed. The calculations further showed that the highest occupied molecular orbital in HPTS3 is an anti-bonding ? orbital on the pyrene rings, followed by lone pair electrons in the peripheral SO3 groups. Negative electron binding energy is a unique feature of multiply-charged anions due to the presence of the repulsive Coulomb barrier. Such metastable species may be good models to study electron-electron and vibronic interactions in complex molecules.

  13. Atomic evidence that modification of H-bonds established with amino acids critical for host-cell binding induces sterile immunity against malaria

    SciTech Connect (OSTI)

    Patarroyo, Manuel E.; Cifuentes, Gladys; Universidad del Rosario, Bogota ; Pirajan, Camilo; Moreno-Vranich, Armando; Vanegas, Magnolia; Universidad Nacional de Colombia, Bogota; Universidad del Rosario, Bogota

    2010-04-09

    Based on the 3D X-ray crystallographic structures of relevant proteins of the malaria parasite involved in invasion to host cells and 3D NMR structures of High Activity Binding Peptides (HABPs) and their respective analogues, it was found that HABPs are rendered into highly immunogenic and sterile immunity inducers in the Aotus experimental model by modifying those amino acids that establish H-bonds with other HABPs or binding to host's cells. This finding adds striking and novel physicochemical principles, at the atomic level, for a logical and rational vaccine development methodology against infectious disease, among them malaria.

  14. A Simple Efficient Method for Obtaining the Binding Energy of Lithium Nucleus under the Hulth\\'en and Inversely Quadratic Yukawa Potentials

    E-Print Network [OSTI]

    Salehi, Nasrin

    2015-01-01

    In this paper, the binding energy of Lithium nucleus in a nonrelativistic model is obtained for the Hulth\\'en and the Inversely Quadratic Yukawa Potential. In order to that, we used the concept of supersymmetry to solving the Schr\\"odinger equation exact analytically. These potentials, due to their physical interpretations, are of interest within many areas of theoretical physics. The results of our model for all calculations show that the ground state binding energy of Lithium nucleus with these potentials are very close to the ones obtained in experiments.

  15. Adhesion Mediated by Competition of Ligand-Receptor Binding Against the Lateral Osmotic Pressure of Mobile Repellers

    E-Print Network [OSTI]

    A. Boulbitch

    2004-08-25

    A model system has been recently developed to study adhesion. It consists of a giant lipid bilayer vesicle with reconstituted lipo-polymers (repellers) as well as with lipo-ligands recognized by receptors covering the substrate. Adhesion in this system is studied theoretically. The state of the weak adhesion is shown to be dominated by the competition of the gravitation and the undulation repulsion between the membrane and the substrate. The state of the tight adhesion is formed by a competition of the ligand-receptor binding and the lateral osmotic pressure of the mobile repeller molecules. The regions of the weak and the tight adhesion are separated on the phase diagram by a whole transition region due to the scattering in parameters of vesicles.

  16. Communication: Towards the binding energy and vibrational red shift of the simplest organic hydrogen bond: Harmonic constraints for methanol dimer

    SciTech Connect (OSTI)

    Heger, Matthias; Suhm, Martin A.; Mata, Ricardo A., E-mail: rmata@gwdg.de [Georg-August-Universitt Gttingen, Institut fr Physikalische Chemie, Tammannstr. 6, 37077 Gttingen (Germany)

    2014-09-14

    The discrepancy between experimental and harmonically predicted shifts of the OH stretching fundamental of methanol upon hydrogen bonding to a second methanol unit is too large to be blamed mostly on diagonal and off-diagonal anharmonicity corrections. It is shown that a decisive contribution comes from post-MP2 electron correlation effects, which appear not to be captured by any of the popular density functionals. We also identify that the major deficiency is in the description of the donor OH bond. Together with estimates for the electronic and harmonically zero-point corrected dimer binding energies, this work provides essential constraints for a quantitative description of this simple hydrogen bond. The spectroscopic dissociation energy is predicted to be larger than 18 kJ/mol and the harmonic OH-stretching fundamental shifts by about ?121 cm{sup ?1} upon dimerization, somewhat more than in the anharmonic experiment (?111 cm{sup ?1})

  17. Binding-induced folding of prokaryotic ubiquitin-like protein on the mycobacterium proteasomal ATPase targets substrates for degradation

    SciTech Connect (OSTI)

    Wang, T.; Li, H.; Darwin, K. H.

    2010-11-01

    Mycobacterium tuberculosis uses a proteasome system that is analogous to the eukaryotic ubiquitin-proteasome pathway and is required for pathogenesis. However, the bacterial analog of ubiquitin, prokaryotic ubiquitin-like protein (Pup), is an intrinsically disordered protein that bears little sequence or structural resemblance to the highly structured ubiquitin. Thus, it was unknown how pupylated proteins were recruited to the proteasome. Here, we show that the Mycobacterium proteasomal ATPase (Mpa) has three pairs of tentacle-like coiled coils that recognize Pup. Mpa bound unstructured Pup through hydrophobic interactions and a network of hydrogen bonds, leading to the formation of an {alpha}-helix in Pup. Our work describes a binding-induced folding recognition mechanism in the Pup-proteasome system that differs mechanistically from substrate recognition in the ubiquitin-proteasome system. This key difference between the prokaryotic and eukaryotic systems could be exploited for the development of a small molecule-based treatment for tuberculosis.

  18. Binding-induced Folding of Prokaryotic Ubiquitin-like Protein on the Mycobacterium Proteasomal ATPase Targets Substrates for Degradation

    SciTech Connect (OSTI)

    T Wang; K Heran Darwin; H Li

    2011-12-31

    Mycobacterium tuberculosis uses a proteasome system that is analogous to the eukaryotic ubiquitin-proteasome pathway and is required for pathogenesis. However, the bacterial analog of ubiquitin, prokaryotic ubiquitin-like protein (Pup), is an intrinsically disordered protein that bears little sequence or structural resemblance to the highly structured ubiquitin. Thus, it was unknown how pupylated proteins were recruited to the proteasome. Here, we show that the Mycobacterium proteasomal ATPase (Mpa) has three pairs of tentacle-like coiled coils that recognize Pup. Mpa bound unstructured Pup through hydrophobic interactions and a network of hydrogen bonds, leading to the formation of an {alpha}-helix in Pup. Our work describes a binding-induced folding recognition mechanism in the Pup-proteasome system that differs mechanistically from substrate recognition in the ubiquitin-proteasome system. This key difference between the prokaryotic and eukaryotic systems could be exploited for the development of a small molecule-based treatment for tuberculosis.

  19. Depletion of cellular poly (A) binding protein prevents protein synthesis and leads to apoptosis in HeLa cells

    SciTech Connect (OSTI)

    Thangima Zannat, Mst.; Bhattacharjee, Rumpa B.; Bag, Jnanankur

    2011-05-13

    Highlights: {yields} Depletion of cellular PABP level arrests mRNA translation in HeLa cells. {yields} PABP knock down leads to apoptotic cell death. {yields} PABP depletion does not affect transcription. {yields} PABP depletion does not lead to nuclear accumulation of mRNA. -- Abstract: The cytoplasmic poly (A) binding protein (PABP) is important in mRNA translation and stability. In yeast, depletion of PABP leads to translation arrest. Similarly, the PABP gene in Drosophila is important for proper development. It is however uncertain, whether mammalian PABP is essential for mRNA translation. Here we showed the effect of PABP depletion on mRNA metabolism in HeLa cells by using a small interfering RNA. Our results suggest that depletion of PABP prevents protein synthesis and consequently leads to cell death through apoptosis. Interestingly, no detectable effect of PABP depletion on transcription, transport and stability of mRNA was observed.

  20. Drosophila nod protein binds preferentially to the plus ends of microtubules and promotes microtubule polymerization in vitro

    E-Print Network [OSTI]

    Hawley, R. Scott; Gilbert, S. P.; Matthies, H. J. G.; Gustafson, S. M.; Sproul, L. R.; Cui, W.

    2005-11-01

    ). The bacterial cultures were continuously grown at 20C for another 4 h. The bacteria were harvested at 6000 rpm for 30 min at 4C, and the bacterial pellets were stored at H1100280C. The E. coli pellets were resuspended in ice-cold native binding buffer (20 m... beads were pelleted at 800 H11003 g for 2 min at 4C and washed in ice-cold washing buffer (20 mM Tris, pH 8.0, 1000 mM NaCl, 20 mM imidazole, 20 mM H9252-mercaptoethanol, 1% Triton X-100, 10% glycerol) four times in the 50-ml conical tube. In the last...

  1. The metalloid arsenite induces nuclear export of Id3 possibly via binding to the N-terminal cysteine residues

    SciTech Connect (OSTI)

    Kurooka, Hisanori, E-mail: hkurooka@u-fukui.ac.jp [Division of Molecular Genetics, Department of Biochemistry and Bioinformative Sciences, School of Medicine, Faculty of Medical Sciences, University of Fukui, Fukui (Japan) [Division of Molecular Genetics, Department of Biochemistry and Bioinformative Sciences, School of Medicine, Faculty of Medical Sciences, University of Fukui, Fukui (Japan); Research and Education Program for Life Science, University of Fukui, Fukui (Japan); Sugai, Manabu [Department of Experimental Therapeutics, Translational Research Center, Kyoto University Hospital, Kyoto (Japan)] [Department of Experimental Therapeutics, Translational Research Center, Kyoto University Hospital, Kyoto (Japan); Mori, Kentaro [Division of Molecular Genetics, Department of Biochemistry and Bioinformative Sciences, School of Medicine, Faculty of Medical Sciences, University of Fukui, Fukui (Japan)] [Division of Molecular Genetics, Department of Biochemistry and Bioinformative Sciences, School of Medicine, Faculty of Medical Sciences, University of Fukui, Fukui (Japan); Yokota, Yoshifumi, E-mail: yokota@u-fukui.ac.jp [Division of Molecular Genetics, Department of Biochemistry and Bioinformative Sciences, School of Medicine, Faculty of Medical Sciences, University of Fukui, Fukui (Japan) [Division of Molecular Genetics, Department of Biochemistry and Bioinformative Sciences, School of Medicine, Faculty of Medical Sciences, University of Fukui, Fukui (Japan); Research and Education Program for Life Science, University of Fukui, Fukui (Japan)

    2013-04-19

    Highlights: Sodium arsenite induces cytoplasmic accumulation of Id3. Arsenite binds to closely spaced N-terminal cysteine residues of Id3. N-terminal cysteines are essential for arsenite-induced nuclear export of Id3. Nuclear export of Id3 counteracts its transcriptional repression activity. -- Abstract: Ids are versatile transcriptional repressors that regulate cell proliferation and differentiation, and appropriate subcellular localization of the Id proteins is important for their functions. We previously identified distinct functional nuclear export signals (NESs) in Id1 and Id2, but no active NES has been reported in Id3. In this study, we found that treatment with the stress-inducing metalloid arsenite led to the accumulation of GFP-tagged Id3 in the cytoplasm. Cytoplasmic accumulation was impaired by a mutation in the Id3 NES-like sequence resembling the Id1 NES, located at the end of the HLH domain. It was also blocked by co-treatment with the CRM1-specific nuclear export inhibitor leptomycin B (LMB), but not with the inhibitors for mitogen-activated protein kinases (MAPKs). Importantly, we showed that the closely spaced N-terminal cysteine residues of Id3 interacted with the arsenic derivative phenylarsine oxide (PAO) and were essential for the arsenite-induced cytoplasmic accumulation, suggesting that arsenite induces the CRM1-dependent nuclear export of Id3 via binding to the N-terminal cysteines. Finally, we demonstrated that Id3 significantly repressed arsenite-stimulated transcription of the immediate-early gene Egr-1 and that this repression activity was inversely correlated with the arsenite-induced nuclear export. Our results imply that Id3 may be involved in the biological action of arsenite.

  2. A Highly Salt-Dependent Enthalpy Change for Escherichia coli SSB Protein-Nucleic Acid Binding Due to Ion-Protein Interactions

    E-Print Network [OSTI]

    Lohman, Timothy M.

    A Highly Salt-Dependent Enthalpy Change for Escherichia coli SSB Protein-Nucleic Acid Binding Due ReceiVed February 5, 1996X ABSTRACT: We have examined the linkage between salt concentration association constant, Kobs, decreases with increasing salt concentration at all temperatures examined

  3. Effect of Inhibitors on the Ubiquinone Binding Capacity of the Primary Energy Conversion Site in the Rhodobacter capsulatus Cytochrome bc1 Complex

    E-Print Network [OSTI]

    Gibney, Brian R.

    Effect of Inhibitors on the Ubiquinone Binding Capacity of the Primary Energy Conversion Site b6f in chloroplasts) comprises the central portion of electron-transfer chains in all energy-transducing organelles. The key primary energy conversion reaction of this complex is the two-electron oxidation

  4. Biochemistry 1993,32. 8299-83 11 8299 Contributions of 2'-Hydroxyl Groups of the RNA Substrate to Binding and

    E-Print Network [OSTI]

    Herschlag, Dan

    Biochemistry 1993,32. 8299-83 11 8299 Contributions of 2'-Hydroxyl Groups of the RNA Substrate'-hydroxyl groups by comparing the binding and reactivity of "chimeric" oligonucleotide substrates,in which contributions from the individual 2'-hydroxyl groups of 13.3 kcal/mol accounts for the 12.2 kcal/mol greater

  5. Binding Strength of Sodium Ions in Cellulose for Different Water Contents M. D. Deshpande,,| Ralph H. Scheicher,*,, Rajeev Ahuja,, and Ravindra Pandey*,

    E-Print Network [OSTI]

    Pandey, Ravi

    Binding Strength of Sodium Ions in Cellulose for Different Water Contents M. D. Deshpande,,| Ralph ions (Na+ ) with cellulose is investigated from first principles for varying degrees of water content OH groups in cellulose which we categorize as two different types. In the absence of water, Na+ forms

  6. Effects of Monovalent Anions on a Temperature-Dependent Heat Capacity Change for Escherichia coli SSB Tetramer Binding to Single-Stranded DNA

    E-Print Network [OSTI]

    Lohman, Timothy M.

    SSB Tetramer Binding to Single-Stranded DNA Alexander G. Kozlov and Timothy M. Lohman* Department, where the subscript denotes the average number of ssDNA nucleotides occluded by each bound tetramer cooperat- ivity (SSB)65 mode in which ssDNA interacts with all four subunits and wraps around the tetramer

  7. Structure of a Glomulin-RBX1-CUL1 Complex: Inhibition of a RING E3 Ligase through Masking of Its E2-Binding Surface

    SciTech Connect (OSTI)

    Duda, David M.; Olszewski, Jennifer L.; Tron, Adriana E.; Hammel, Michal; Lambert, Lester J.; Waddell, M. Brett; Mittag, Tanja; DeCaprio, James A.; Schulman, Brenda A. (BWH); (LBNL); (SJCH); (DFCI)

    2012-11-01

    The approximately 300 human cullin-RING ligases (CRLs) are multisubunit E3s in which a RING protein, either RBX1 or RBX2, recruits an E2 to catalyze ubiquitination. RBX1-containing CRLs also can bind Glomulin (GLMN), which binds RBX1's RING domain, regulates the RBX1-CUL1-containing SCF{sup FBW7} complex, and is disrupted in the disease Glomuvenous Malformation. Here we report the crystal structure of a complex between GLMN, RBX1, and a fragment of CUL1. Structural and biochemical analyses reveal that GLMN adopts a HEAT-like repeat fold that tightly binds the E2-interacting surface of RBX1, inhibiting CRL-mediated chain formation by the E2 CDC34. The structure explains the basis for GLMN's selectivity toward RBX1 over RBX2, and how disease-associated mutations disrupt GLMN-RBX1 interactions. Our study reveals a mechanism for RING E3 ligase regulation, whereby an inhibitor blocks E2 access, and raises the possibility that other E3s are likewise controlled by cellular proteins that mask E2-binding surfaces to mediate inhibition.

  8. On the Stator of Rotary ATP Synthase: The Binding Strength of Subunit to (R )3 As Determined by Fluorescence Correlation Spectroscopy

    E-Print Network [OSTI]

    Junge, Wolfgang

    On the Stator of Rotary ATP Synthase: The Binding Strength of Subunit to (R )3 As Determined; ReVised Manuscript ReceiVed July 20, 1999 ABSTRACT: ATP synthase is conceived as a rotary enzyme2c12. ATP synthase is conceived as a molecular engine (3-5). The hydrolysis of ATP drives

  9. J. Phys. Chem. 1994, 98, 5113-5111 5773 Free Energy of Solvation, Interaction, and Binding of Arbitrary Charge Distributions Imbedded in

    E-Print Network [OSTI]

    Jayaram, Bhyravabotla

    J. Phys. Chem. 1994, 98, 5113-5111 5773 Free Energy of Solvation, Interaction, and Binding in a continuum solvent. Background Attempts seeking analytical solutions to the hydration free energies solvation free energies of arbitrary charge distributions with an overall spherical symmetry. This theory

  10. A modeling assessment of the interplay between aeolian iron fluxes and iron-binding ligands in controlling carbon dioxide fluctuations during

    E-Print Network [OSTI]

    Fortunat, Joos

    in controlling carbon dioxide fluctuations during Antarctic warm events Payal Parekh,1 Fortunat Joos,1 between aeolian iron fluxes and iron-binding ligands in controlling carbon dioxide fluctuations during decreasing atmospheric carbon dioxide (CO2). This is consistent with evidence of an increase in the aeolian

  11. PLASMA MEMBRANE GLYCOPKOTEINS OF MATURE AND IMMA'I`UKE DRONE HONEY BEE (Apis mellifera I_) SPERMATOZOA: LECI'IN-BINDING AS SEEN BY LIGHT AND ELECTRON

    E-Print Network [OSTI]

    Zaragoza, Universidad de

    ELSEVIER PLASMA MEMBRANE GLYCOPKOTEINS OF MATURE AND IMMA'I`UKE DRONE HONEY BEE (Apis mellifera I in spermatozoa of A isa drones, may play a role in oocyte-spermatozoon recognition. We studied the distribution of the glycoproteins and changes in their composition associated with maturation of the drones, using lectin binding

  12. Identification of High Affinity Polo-like Kinase 1 (Plk1) Polo-box Domain Binding Peptides Using Oxime-Based Diversification

    E-Print Network [OSTI]

    Liu, Fa

    In an effort to develop improved binding antagonists of the polo-like kinase 1 (Plk1) polo-box domain (PBD), we optimized interactions of the known high affinity 5-mer peptide PLHSpT using oxime-based post solid-phase ...

  13. The binding affinity of a soluble TCR-Fc fusion protein is significantly improved by crosslinkage with an anti-C{beta} antibody

    SciTech Connect (OSTI)

    Ozawa, Tatsuhiko; Horii, Masae; Kobayashi, Eiji [Department of Immunology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194 (Japan)] [Department of Immunology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194 (Japan); Jin, Aishun [Department of Immunology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194 (Japan) [Department of Immunology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194 (Japan); Department of Immunology, College of Basic Medical Sciences, Harbin Medical University, 157 Baojian Road, Nangang District, Harbin 150081 (China); Kishi, Hiroyuki, E-mail: immkishi@med.u-toyama.ac.jp [Department of Immunology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194 (Japan)] [Department of Immunology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194 (Japan); Muraguchi, Atsushi [Department of Immunology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194 (Japan)] [Department of Immunology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194 (Japan)

    2012-06-01

    Highlights: Black-Right-Pointing-Pointer A novel soluble TCR composed of TCR V and C regions with Ig Fc region is generated. Black-Right-Pointing-Pointer TCR-Fc protein immobilized by an anti-C{beta} antibody bound to a p/MHC tetramer. Black-Right-Pointing-Pointer Binding affinity of TCR-Fc was markedly increased by binding with anti-C{beta} antibody. -- Abstract: The identification and cloning of tumor antigen-specific T cell receptors (TCRs) and the production of the soluble form of the TCR (sTCR) contributed to the development of diagnostic and therapeutic tools for cancer. Recently, several groups have reported the development of technologies for the production of sTCRs. The native sTCR has a very low binding affinity for the antigenic peptide/MHC (p/MHC) complex. In this study, we established a technology to produce high affinity, functional sTCRs. We generated a novel sTCR-Fc fusion protein composed of the TCR V and C regions of the TCR linked to the immunoglobulin (Ig) Fc region. A Western blot analysis revealed that the molecular weight of the fusion protein was approximately 60 kDa under reducing conditions and approximately 100-200 kDa under non-reducing conditions. ELISAs using various antibodies showed that the structure of each domain of the TCR-Fc protein was intact. The TCR-Fc protein immobilized by an anti-C{beta} antibody effectively bound to a p/MHC tetramer. An SPR analysis showed that the TCR-Fc protein had a low binding affinity (KD; 1.1 Multiplication-Sign 10{sup -5} M) to the p/MHC monomer. Interestingly, when the TCR-Fc protein was pre-incubated with an anti-C{beta} antibody, its binding affinity for p/MHC increased by 5-fold (2.2 Multiplication-Sign 10{sup -6} M). We demonstrated a novel method for constructing a functional soluble TCR using the Ig Fc region and showed that the binding affinity of the functional sTCR-Fc was markedly increased by an anti-C{beta} antibody, which is probably due to the stabilization of the V{alpha}/V{beta} region of the TCR. These findings provide new insights into the binding of sTCRs to p/MHCs and will hopefully be instrumental in establishing functional sTCR as a diagnostic and therapeutic tool for cancer.

  14. UNC-45/CRO1/She4p (UCS) Protein Forms Elongated Dimer and Joins Two Myosin Heads Near Their Actin Binding Region

    SciTech Connect (OSTI)

    H Shi; G Blobel

    2011-12-31

    UNC-45/CRO1/She4p (UCS) proteins have variously been proposed to affect the folding, stability, and ATPase activity of myosins. They are the only proteins known to interact directly with the motor domain. To gain more insight into UCS function, we determined the atomic structure of the yeast UCS protein, She4p, at 2.9 {angstrom} resolution. We found that 16 helical repeats are organized into an L-shaped superhelix with an amphipathic N-terminal helix dangling off the short arm of the L-shaped molecule. In the crystal, She4p forms a 193-{angstrom}-long, zigzag-shaped dimer through three distinct and evolutionary conserved interfaces. We have identified She4p's C-terminal region as a ligand for a 27-residue-long epitope on the myosin motor domain. Remarkably, this region consists of two adjacent, but distinct, binding epitopes localized at the nucleotide-responsive cleft between the nucleotide- and actin-filament-binding sites. One epitope is situated inside the cleft, the other outside the cleft. After ATP hydrolysis and Pi ejection, the cleft narrows at its base from 20 to 12 {angstrom} thereby occluding the inside the cleft epitope, while leaving the adjacent, outside the cleft binding epitope accessible to UCS binding. Hence, one cycle of higher and lower binding affinity would accompany one ATP hydrolysis cycle and a single step in the walk on an actin filament rope. We propose that a UCS dimer links two myosins at their motor domains and thereby functions as one of the determinants for step size of myosin on actin filaments.

  15. Structural Basis of Low-Affinity Nickel Binding to the Nickel-Responsive Transcription Factor NikR from Escherichia coli

    SciTech Connect (OSTI)

    Phillips, C.; Schreiter, E; Stultz, C; Drennan, C

    2010-01-01

    Escherichia coli NikR regulates cellular nickel uptake by binding to the nik operon in the presence of nickel and blocking transcription of genes encoding the nickel uptake transporter. NikR has two binding affinities for the nik operon: a nanomolar dissociation constant with stoichiometric nickel and a picomolar dissociation constant with excess nickel [Bloom, S. L., and Zamble, D. B. (2004) Biochemistry 43, 10029-10038; Chivers, P. T., and Sauer, R. T. (2002) Chem. Biol. 9, 1141-1148]. While it is known that the stoichiometric nickel ions bind at the NikR tetrameric interface [Schreiter, E. R., et al. (2003) Nat. Struct. Biol. 10, 794-799; Schreiter, E. R., et al. (2006) Proc. Natl. Acad. Sci. U.S.A. 103, 13676-13681], the binding sites for excess nickel ions have not been fully described. Here we have determined the crystal structure of NikR in the presence of excess nickel to 2.6 {angstrom} resolution and have obtained nickel anomalous data (1.4845 {angstrom}) in the presence of excess nickel for both NikR alone and NikR cocrystallized with a 30-nucleotide piece of double-stranded DNA containing the nik operon. These anomalous data show that excess nickel ions do not bind to a single location on NikR but instead reveal a total of 22 possible low-affinity nickel sites on the NikR tetramer. These sites, for which there are six different types, are all on the surface of NikR, and most are found in both the NikR alone and NikR-DNA structures. Using a combination of crystallographic data and molecular dynamics simulations, the nickel sites can be described as preferring octahedral geometry, utilizing one to three protein ligands (typically histidine) and at least two water molecules.

  16. Monte-Carlo simulation of the tight-binding model of graphene with partially screened Coulomb interactions

    E-Print Network [OSTI]

    Dominik Smith; Lorenz von Smekal

    2014-03-14

    We report on Hybrid-Monte-Carlo simulations of the tight-binding model with long-range Coulomb interactions for the electronic properties of graphene. We investigate the spontaneous breaking of sublattice symmetry corresponding to a transition from the semimetal to an antiferromagnetic insulating phase. Our short-range interactions thereby include the partial screening due to electrons in higher energy states from ab initio calculations based on the constrained random phase approximation [T.O.Wehling {\\it et al.}, Phys.Rev.Lett.{\\bf 106}, 236805 (2011)]. In contrast to a similar previous Monte-Carlo study [M.V.Ulybyshev {\\it et al.}, Phys.Rev.Lett.{\\bf 111}, 056801 (2013)] we also include a phenomenological model which describes the transition to the unscreened bare Coulomb interactions of graphene at half filling in the long-wavelength limit. Our results show, however, that the critical coupling for the antiferromagnetic Mott transition is largely insensitive to the strength of these long-range Coulomb tails. They hence confirm the prediction that suspended graphene remains in the semimetal phase when a realistic static screening of the Coulomb interactions is included.

  17. Correlating the hydrogen evolution reaction activity in alkaline electrolytes with the hydrogen binding energy on monometallic surfaces

    SciTech Connect (OSTI)

    Sheng, WC; Myint, M; Chen, JGG; Yan, YS

    2013-05-01

    The slow reaction kinetics of the hydrogen evolution and oxidation reactions (HER/HOR) on platinum in alkaline electrolytes hinders the development of alkaline electrolysers, solar hydrogen cells and alkaline fuel cells. A fundamental understanding of the exchange current density of the HER/HOR in alkaline media is critical for the search and design of highly active electrocatalysts. By studying the HER on a series of monometallic surfaces, we demonstrate that the HER exchange current density in alkaline solutions can be correlated with the calculated hydrogen binding energy (HBE) on the metal surfaces via a volcano type of relationship. The HER activity varies by several orders of magnitude from Pt at the peak of the plot to W and Au located on the bottom of each side of the plot, similar to the observation in acids. Such a correlation suggests that the HBE can be used as a descriptor for identifying electrocatalysts for HER/HOR in alkaline media, and that the HER exchange current density can be tuned by modifying the surface chemical properties.

  18. A New Determination of the Binding Energy of Atomic Oxygen on Dust Grain Surfaces: Experimental Results and Simulations

    E-Print Network [OSTI]

    He, Jiao; Hopkins, Tyler; Vidali, Gianfranco; Kaufman, Michael J

    2015-01-01

    The energy to desorb atomic oxygen from an interstellar dust grain surface, $E_{\\rm des}$, is an important controlling parameter in gas-grain models; its value impacts the temperature range over which oxygen resides on a dust grain. However, no prior measurement has been done of the desorption energy. We report the first direct measurement of $E_{\\rm des}$ for atomic oxygen from dust grain analogs. The values of $E_{\\rm des}$ are $1660\\pm 60$~K and $1850\\pm 90$~K for porous amorphous water ice and for a bare amorphous silicate film, respectively, or about twice the value previously adopted in simulations of the chemical evolution of a cloud. We use the new values to study oxygen chemistry as a function of depth in a molecular cloud. For $n=10^4$ cm$^{-3}$ and $G_0$=10$^2$ ($G_0$=1 is the average local interstellar radiation field), the main result of the adoption of the higher oxygen binding energy is that H$_2$O can form on grains at lower visual extinction $A_{\\rm V}$, closer to the cloud surface. A higher ...

  19. Study of quark mass dependence of binding energy for light nuclei in 2+1 flavor lattice QCD

    E-Print Network [OSTI]

    Takeshi Yamazaki; Ken-ichi Ishikawa; Yoshinobu Kuramashi; Akira Ukawa

    2015-07-03

    We investigate the formation of light nuclei with the nuclear mass number less than or equal to four in 2+1 flavor QCD using a non-perturbative improved Wilson quark and Iwasaki gauge actions. The quark mass is decreased from our previous work to the one corresponding to the pion mass of 0.30 GeV. In each multi-nucleon channel, the energy shift of the ground state relative to the assembly of free nucleons is calculated on two volumes, whose spatial extents are 4.3 fm and 5.8 fm. From the volume dependence of the energy shift, we distinguish a bound state of multi nucleons from an attractive scattering state. We find that all the ground states measured in this calculation are bound states. As in the previous studies at larger $m_\\pi$, our result indicates that at $m_\\pi = 0.30$ GeV the effective interaction between nucleons in the light nuclei is relatively stronger than the one in nature, since the results for the binding energies are larger than the experimental values and a bound state appears in the dineutron channel, which is not observed in experiment. Possible sources of systematic error in this calculation are discussed.

  20. Carbonation as a binding mechanism for coal/calcium hydroxide pellets. Technical report, December 1, 1991--February 29, 1992

    SciTech Connect (OSTI)

    Rapp, D.M. Ehrlinger, H.P.; Hackley, K.C.; Lytle, J.M.; Moran, D.L. [Illinois State Geological Survey, Champaign, IL (United States); Berger, R.L. [Univ. Illinois, Champaign, IL (United States). Dept. of Civil Engineering; Schanche, G. [Army Construction Engineering Research Lab., Champaign, IL (United States); Chow, Poo [Univ. Illinois, Champaign, IL (United States). Dept. of Forestry; Strickland, R. [Tennessee Valley Authority, Muscle Shoals, AL (United States)

    1992-09-01

    In this project supported by the CRSC, the Tennessee Valley Authority (TVA) and the Engineering Research Laboratory (CERL), ISGS is investigating the pelletization of fine coal with calcium hydroxide, a sulfur capturing sorbent. The objective is to produce a readily-transportable fuel which will burn in compliance with the recently passed Clean Air Act Amendments. To improve the economics of pelletization, carbonation, or, the reaction of carbon dioxide with calcium hydroxide to produce a binding matrix of calcium carbonate, is being investigated as a method of hardening pelletized coal fines. Previous results indicate that carbonation significantly improves pellet quality including serving to weatherproof the pellets. During this quarter, work was conducted on several topics. Calcium oxide was investigated as a potentially lower cost binder than calcium hydroxide and was determined to be of comparable effectiveness on a molar basis indicating some potential for an overall cost savings. The effect of pellet size on pellet quality was also investigated. Results indicate that 1/4 and 1/2-inch diameter pellets have similar compressive strengths when compared on the basis of pounds per square inch crushing pressure. Also a low cost starch was tested as an alternative binder. Although cheaper per pound than a starch binder previously tested, it was not less expensive when evaluated on the basis of pellet quality attained.

  1. Structure of trigger factor binding domain in biologically homologous complex with eubacterial ribosome reveals its chaperone action

    SciTech Connect (OSTI)

    Baram, David; Pyetan, Erez; Sittner, Assa; Auerbach-Nevo, Tamar; Bashan, Anat; Yonath, Ada (WIS-I)

    2010-07-13

    Trigger factor (TF), the first chaperone in eubacteria to encounter the emerging nascent chain, binds to the large ribosomal subunit in the vicinity of the protein exit tunnel opening and forms a sheltered folding space. Here, we present the 3.5-{angstrom} crystal structure of the physiological complex of the large ribosomal subunit from the eubacterium Deinococcus radiodurans with the N-terminal domain of TF (TFa) from the same organism. For anchoring, TFa exploits a small ribosomal surface area in the vicinity of proteins L23 and L29, by using its 'signature motif' as well as additional structural elements. The molecular details of TFa interactions reveal that L23 is essential for the association of TF with the ribosome and may serve as a channel of communication with the nascent chain progressing in the tunnel. L29 appears to induce a conformational change in TFa, which results in the exposure of TFa hydrophobic patches to the opening of the ribosomal exit tunnel, thus increasing its affinity for hydrophobic segments of the emerging nascent polypeptide. This observation implies that, in addition to creating a protected folding space for the emerging nascent chain, TF association with the ribosome prevents aggregation by providing a competing hydrophobic environment and may be critical for attaining the functional conformation necessary for chaperone activity.

  2. Insights into Regulated Ligand Binding Sites from the Structure of ZO-1 Src Homology 3-Guanylate Kinase Module

    SciTech Connect (OSTI)

    Lye, Ming F.; Fanning, Alan S.; Su, Ying; Anderson, James M.; Lavie, Arnon (UNC); (UIC)

    2010-11-09

    Tight junctions are dynamic components of epithelial and endothelial cells that regulate the paracellular transport of ions, solutes, and immune cells. The assembly and permeability of these junctions is dependent on the zonula occludens (ZO) proteins, members of the membrane-associated guanylate kinase homolog (MAGUK) protein family, which are characterized by a core Src homology 3 (SH3)-GUK module that coordinates multiple protein-protein interactions. The structure of the ZO-1 SH3-GUK domain confirms that the interdependent folding of the SH3 and GUK domains is a conserved feature of MAGUKs, but differences in the orientation of the GUK domains in three different MAGUKs reveal interdomain flexibility of the core unit. Using pull-down assays, we show that an effector loop, the U6 region in ZO-1, forms a novel intramolecular interaction with the core module. This interaction is divalent cation-dependent and overlaps with the binding site for the regulatory molecule calmodulin on the GUK domain. These findings provide insight into the previously observed ability of the U6 region to regulate TJ assembly in vivo and the structural basis for the complex protein interactions of the MAGUK family.

  3. Strain-Specific V3 and CD4 Binding Site Autologous HIV-1 Neutralizing Antibodies Select Neutralization-Resistant Viruses

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Moody, M. Anthony; Gao, Feng; Gurley, Thaddeus C.; Amos, Joshua D.; Kumar, Amit; Hora, Bhavna; Marshall, Dawn J.; Whitesides, John F.; Xia, Shi-Mao; Parks, Robert; et al

    2015-09-09

    The third variable (V3) loop and the CD4 binding site (CD4bs) of the viral envelope are frequently targeted by neutralizing antibodies (nAbs) in HIV-1-infected individuals. In chronic infection, virus escape mutants repopulate the plasma and V3 and CD4bs nAbs emerge that can neutralize heterologous tier 1 easy-to-neutralize, but not tier 2 difficult-to-neutralize HIV-1 isolates. However, neutralization sensitivity of autologous plasma viruses to this type of nAb response has not been studied. We describe the development and evolution in vivo of antibodies distinguished by their target specificity for V3and CD4bs epitopes on autologous tier 2 viruses but not on heterologous tiermore2 viruses. A surprisingly high fraction of autologous circulating viruses was sensitive to these antibodies. These findings demonstrate a role for V3 and CD4bs antibodies in constraining the native envelope trimer in vivo to a neutralization-resistant phenotype, explaining why HIV-1 transmission generally occurs by tier 2 neutralization-resistant viruses.less

  4. hnRNP L binds to CA repeats in the 3'UTR of bcl-2 mRNA

    SciTech Connect (OSTI)

    Lee, Dong-Hyoung; Lim, Mi-Hyun; Youn, Dong-Ye [Department of Biochemistry, College of Medicine, The Catholic University of Korea, 505 Banpo-Dong, Seocho-gu, Seoul 137-701 (Korea, Republic of)] [Department of Biochemistry, College of Medicine, The Catholic University of Korea, 505 Banpo-Dong, Seocho-gu, Seoul 137-701 (Korea, Republic of); Jung, Seung Eun [Department of Medical Science, The Graduate School, Yonsei University, Seoul (Korea, Republic of)] [Department of Medical Science, The Graduate School, Yonsei University, Seoul (Korea, Republic of); Ahn, Young Soo [Brain Korea 21 Project for Medical Science, Brain Research Institute, Department of Pharmacology, Yonsei University College of Medicine, Seoul (Korea, Republic of)] [Brain Korea 21 Project for Medical Science, Brain Research Institute, Department of Pharmacology, Yonsei University College of Medicine, Seoul (Korea, Republic of); Tsujimoto, Yoshihide [Department of Medical Genetics, Laboratory of Molecular Genetics, Osaka University Medical School, Osaka (Japan)] [Department of Medical Genetics, Laboratory of Molecular Genetics, Osaka University Medical School, Osaka (Japan); Lee, Jeong-Hwa, E-mail: leejh@catholic.ac.kr [Department of Biochemistry, College of Medicine, The Catholic University of Korea, 505 Banpo-Dong, Seocho-gu, Seoul 137-701 (Korea, Republic of)] [Department of Biochemistry, College of Medicine, The Catholic University of Korea, 505 Banpo-Dong, Seocho-gu, Seoul 137-701 (Korea, Republic of)

    2009-05-08

    We previously reported that the CA-repeat sequence in the 3'-untranslated region (3'UTR) of bcl-2 mRNA is involved in the decay of bcl-2 mRNA. However, the trans-acting factor for the CA element in bcl-2 mRNA remains unidentified. The heterogeneous nuclear ribonucleoprotein L (hnRNP L), an intron splicing factor, has been reported to bind to CA repeats and CA clusters in the 3'UTR of several genes. We reported herein that the CA repeats of bcl-2 mRNA have the potential to form a distinct ribonuclear protein complex in cytoplasmic extracts of MCF-7 cells, as evidenced by RNA electrophoretic mobility shift assays (REMSA). A super-shift assay using the hnRNP L antibody completely shifted the complex. Immunoprecipitation with the hnRNP L antibody and MCF-7 cells followed by RT-PCR revealed that hnRNP L interacts with endogenous bcl-2 mRNA in vivo. Furthermore, the suppression of hnRNP L in MCF-7 cells by the transfection of siRNA for hnRNP L resulted in a delay in the degradation of RNA transcripts including CA repeats of bcl-2 mRNA in vitro, suggesting that the interaction between hnRNPL and CA repeats of bcl-2 mRNA participates in destabilizing bcl-2 mRNA.

  5. Structure of the unique SEFIR domain from human interleukin 17 receptor A reveals a composite ligand-binding site containing a conserved ?-helix for Act1 binding and IL-17 signaling

    SciTech Connect (OSTI)

    Zhang, Bing [Oklahoma State University, Stillwater, OK 74078 (United States); Liu, Caini; Qian, Wen [Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195 (United States); Han, Yue [Oklahoma State University, Stillwater, OK 74078 (United States); Li, Xiaoxia, E-mail: lix@ccf.org [Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195 (United States); Deng, Junpeng, E-mail: lix@ccf.org [Oklahoma State University, Stillwater, OK 74078 (United States)

    2014-05-01

    Crystal structure of the SEFIR domain from human IL-17 receptor A provides new insights into IL-17 signaling. Interleukin 17 (IL-17) cytokines play a crucial role in mediating inflammatory and autoimmune diseases. A unique intracellular signaling domain termed SEFIR is found within all IL-17 receptors (IL-17Rs) as well as the key adaptor protein Act1. SEFIR-mediated proteinprotein interaction is a crucial step in IL-17 cytokine signaling. Here, the 2.3 resolution crystal structure of the SEFIR domain of IL-17RA, the most commonly shared receptor for IL-17 cytokine signaling, is reported. The structure includes the complete SEFIR domain and an additional ?-helical C-terminal extension, which pack tightly together to form a compact unit. Structural comparison between the SEFIR domains of IL-17RA and IL-17RB reveals substantial differences in protein topology and folding. The uniquely long insertion between strand ?C and helix ?C in IL-17RA SEFIR is mostly well ordered, displaying a helix (?CC?{sub ins}) and a flexible loop (CC?). The DD? loop in the IL-17RA SEFIR structure is much shorter; it rotates nearly 90 with respect to the counterpart in the IL-17RB SEFIR structure and shifts about 12 to accommodate the ?CC?{sub ins} helix without forming any knots. Helix ?C was identified as critical for its interaction with Act1 and IL-17-stimulated gene expression. The data suggest that the heterotypic SEFIRSEFIR association via helix ?C is a conserved and signature mechanism specific for IL-17 signaling. The structure also suggests that the downstream motif of IL-17RA SEFIR together with helix ?C could provide a composite ligand-binding surface for recruiting Act1 during IL-17 signaling.

  6. Structure of the vesicular stomatitis virus nucleocapsid in complex with the nucleocapsid-binding domain of the small polymerase cofactor, P

    SciTech Connect (OSTI)

    Green, Todd J.; Luo, Ming

    2009-10-05

    The negative-strand RNA viruses (NSRVs) are unique because their nucleocapsid, not the naked RNA, is the active template for transcription and replication. The viral polymerase of nonsegmented NSRVs contains a large polymerase catalytic subunit (L) and a nonenzymatic cofactor, the phosphoprotein (P). Insight into how P delivers the polymerase complex to the nucleocapsid has long been pursued by reverse genetics and biochemical approaches. Here, we present the X-ray crystal structure of the C-terminal domain of P of vesicular stomatitis virus, a prototypic nonsegmented NSRV, bound to nucleocapsid-like particles. P binds primarily to the C-terminal lobe of 2 adjacent N proteins within the nucleocapsid. This binding mode is exclusive to the nucleocapsid, not the nucleocapsid (N) protein in other existing forms. Localization of phosphorylation sites within P and their proximity to the RNA cavity give insight into how the L protein might be oriented to access the RNA template.

  7. Effect of Dielectric Properties of Ceramic-Solvent Interface on the Binding of Protein to Oxide Ceramics: a Non Local Electrostatic Approach

    E-Print Network [OSTI]

    Rubinstein, A I; Namavar, F

    2014-01-01

    The contribution of electrostatic interactions to the free energy of binding between model protein and a ceramic implant surface in the aqueous solvent, considered in the framework of the non-local electrostatic model, is calculated as a function of the implant low-frequency dielectric constant. We show that the existence of a dynamically ordered (low-dielectric) interfacial solvent layer at the protein-solvent and ceramic-solvent interface markedly increases charging energy of the protein and ceramic implant, and consequently makes the electrostatic contribution to the protein-ceramic binding energy more favorable (attractive). Our analysis shows that the corresponding electrostatic energy between protein and oxide ceramics depends non-monotonically on the dielectric constant of ceramic. Obtained results indicate that protein can attract electrostatically to the surface if ceramic material has a moderate dielectric constant below or about 35 (in particularly ZrO2 or Ta2O5). This is in contrast to classical (...

  8. Site occupancy and cation binding states in reduced polycrystalline Sr{sub x}Ba{sub 1?x}Nb{sub 2}O{sub 6}

    SciTech Connect (OSTI)

    Dandeneau, Christopher S., E-mail: dandec@u.washington.edu; Yang, YiHsun; Ohuchi, Fumio S. [Department of Materials Science and Engineering, University of Washington, Seattle, Washington 98195 (United States)] [Department of Materials Science and Engineering, University of Washington, Seattle, Washington 98195 (United States); Krueger, Benjamin W.; Olmstead, Marjorie A. [Department of Physics, University of Washington, Seattle, Washington 98195 (United States)] [Department of Physics, University of Washington, Seattle, Washington 98195 (United States); Bordia, Rajendra K. [Department of Materials Science and Engineering, Clemson University, Clemson, South Carolina 29634 (United States)] [Department of Materials Science and Engineering, Clemson University, Clemson, South Carolina 29634 (United States)

    2014-03-10

    Site occupancy and cation binding states in the proposed thermoelectric n-type oxide Sr{sub x}Ba{sub 1?x}Nb{sub 2}O{sub 6} (SBN100x) were investigated using X-ray photoelectron spectroscopy (XPS). Sr 3d XPS spectra from unreduced polycrystalline SBN100x with various compositions contained two distinct spin-orbit doublets corresponding to Sr occupying either A1 or A2 positions in the SBN lattice; the higher binding energy state was associated with Sr ions at A2 sites, presumably due to their increased coordination over Sr at A1 sites. To gain insight into optimizing the thermoelectric properties of reduced SBN, sintered SBN50 specimens were reduced in Ar/H{sub 2} or N{sub 2}/H{sub 2} ambient. A decrease in the average Nb valence was observed in Nb 3d photoemission through the growth of low-binding energy components after reduction in either environment; evidence of surface NbN formation was apparent with longer reducing times in N{sub 2}/H{sub 2}. Both the single-component Ba 3d emission and the A2 component of the Sr 3d spectra show shifting to lower binding energy as the reduction time is increased, supporting the hypothesis of preferential oxygen vacancy formation adjacent to A2 sites. X-ray diffraction patterns revealed the formation of NbO{sub 2} in both reducing environments; in the case of extended reduction in N{sub 2}/H{sub 2}, NbO{sub 2} is gradually converted to NbN phases. Given the known properties of metallic NbN and semiconducting NbO{sub 2}, the findings obtained here may be used to maximize the thermoelectric performance of SBN via the fabrication of composite structures containing both NbO{sub 2} and NbN.

  9. Volume 139, number 1 FEBS LETTER? March 1982 DNA BINDING OF CAMP RECEPTOR PROTEIN AND ITS N-TERMJNAL CORE STABILIZES

    E-Print Network [OSTI]

    Clore, G. Marius

    the initiation of mBNA synthesis in the presence of CAMP[l-7]. The smaller carboxy- terminal domain of both of binding and of initiation of mBNA synthesis by RNA polymerase [8]. This model was suggested on the basis on the 2.9 A resolution crystal structure of the CAMP-CBP complex [8]. If this hypothesis is correct, the N

  10. Schistosoma mansoni venom allergen-like protein 4 (SmVAL4) is a novel lipid-binding SCP/TAPS protein that lacks the prototypical CAP motifs

    SciTech Connect (OSTI)

    Kelleher, Alan [Baylor College of Medicine, Houston, TX 77030 (United States); Darwiche, Rabih [University of Fribourg, Chemin du Muse 10, CH 1700 Fribourg (Switzerland); Rezende, Wanderson C. [Baylor College of Medicine, Houston, TX 77030 (United States); Farias, Leonardo P.; Leite, Luciana C. C. [Instituto Butantan, So Paulo, SP (Brazil); Schneiter, Roger [University of Fribourg, Chemin du Muse 10, CH 1700 Fribourg (Switzerland); Asojo, Oluwatoyin A., E-mail: asojo@bcm.edu [Baylor College of Medicine, Houston, TX 77030 (United States)

    2014-08-01

    The first structure of an S. mansoni venom allergen-like protein is presented. Schistosomiasis is a parasitic disease that affects over 200 million people. Vaccine candidates have been identified, including Schistosoma mansoni venom allergen-like proteins (SmVALs) from the SCP/TAPS (sperm-coating protein/Tpx/antigen 5/pathogenesis related-1/Sc7) superfamily. The first SmVAL structure, SmVAL4, was refined to a resolution limit of 2.16 . SmVAL4 has a unique structure that could not be predicted from homologous structures, with longer loops and an unusual C-terminal extension. SmVAL4 has the characteristic ?/?-sandwich and central SCP/TAPS cavity. Furthermore, SmVAL4 has only one of the signature CAP cavity tetrad amino-acid residues and is missing the histidines that coordinate divalent cations such as Zn{sup 2+} in other SCP/TAPS proteins. SmVAL4 has a cavity between ?-helices 1 and 4 that was observed to bind lipids in tablysin-15, suggesting the ability to bind lipids. Subsequently, SmVAL4 was shown to bind cholesterol in vitro. Additionally, SmVAL4 was shown to complement the in vivo sterol-export phenotype of yeast mutants lacking their endogenous CAP proteins. Expression of SmVAL4 in yeast cells lacking endogenous CAP function restores the block in sterol export. These studies suggest an evolutionarily conserved lipid-binding function shared by CAP proteins such as SmVAL4 and yeast CAP proteins such as Pry1.

  11. An analysis of van der Waals density functional components: Binding and corrugation of benzene and C60 on boron nitride and graphene

    E-Print Network [OSTI]

    Berland, Kristian

    2013-01-01

    The adsorption of benzene and C60 on graphene and boron nitride (BN) is studied using density functional theory with the non-local correlation functional vdW-DF. By comparing these systems we can systematically investigate their adsorption nature and differences between the two functional versions vdW-DF1 and vdW-DF2. The bigger size of the C60 molecule makes it bind stronger to the surface than benzene, yet the interface between the molecules and the sheets are similar in nature. The binding separation is more sensitive to the exchange variant used in vdW-DF than to the correlation version. This result is related to the exchange and correlation components of the potential energy curve (PEC). We show that a moderate dipole forms for C60 on graphene, unlike for the other adsorption systems. We find that the corrugation is very sensitive to the variant or version of vdW-DF used, in particular the exchange. Further, we show that this sensitivity arise indirectly through the shift in binding separation caused by ...

  12. Binding of the Respiratory Chain Inhibitor Antimycin to theMitochondrial bc1 Complex: A New Crystal Structure Reveals an AlteredIntramolecular Hydrogen-Bonding Pattern

    SciTech Connect (OSTI)

    Huang, Li-shar; Cobessi, David; Tung, Eric Y.; Berry, Edward A.

    2005-05-10

    Antimycin A (antimycin), one of the first known and most potent inhibitors of the mitochondrial respiratory chain, binds to the quinone reduction site of the cytochrome bc1 complex.Structure-activity-relationship studies have shown that the N-formylamino-salicyl-amide group is responsible for most of the binding specificity, and suggested that a low pKa for the phenolic OH group and an intramolecular H-bond between that OH and the carbonyl O of the salicylamide linkage are important. Two previous X-ray structures of antimycin bound to vertebrate bc1 complex gave conflicting results. A new structure reported here of the bovine mitochondrial bc1 complex at 2.28Angstrom resolution with antimycin bound, allows us for the first time to reliably describe the binding of antimycin and shows that the intramolecular hydrogen bond described in solution and in the small-molecule structure is replaced by one involving the NH rather than carbonyl O of the amide linkage, with rotation of the amide group relative to the aromatic ring. The phenolic OH and formylamino N form H-bonds with conserved Asp228 of cyt b, and the formylamino O H-bonds via a water molecule to Lys227. A strong density the right size and shape for a diatomic molecule is found between the other side of the dilactone ring and the alpha-A helix.

  13. Influenza A H3N2 subtype virus NS1 protein targets into the nucleus and binds primarily via its C-terminal NLS2/NoLS to nucleolin and fibrillarin

    E-Print Network [OSTI]

    Meln, Krister; Tynell, Janne; Fagerlund, Riku; Roussel, Pascal; Hernandez-Verdun, Danile; Julkunen, Ilkka

    2012-01-01

    Influenza A H3N2 subtype virus NS1 protein targets into theBinding of the influenza A virus NS1 protein to PKR mediatespathogenic H5N1 influenza virus. Nature 2008, 456:985988.

  14. Structural and Functional Studies of the Receptor-binding and Glycosaminogly-canbinding Mechanisms of a Viral Chemokine Analog vMIP-II and Rational Design of Chemokine-based Highly Potent HIV-1 Entry Inhibitors

    E-Print Network [OSTI]

    Zhao, Bo

    2012-07-16

    Chemokines are small immune system proteins mediating leukocyte migration and activation, and are important in many aspects of health and diseases. Some chemokines also have the ability to block HIV-1 infection by binding ...

  15. The PD-1/PD-L1 complex resembles the antigen-binding Fv domains of antibodies and T cell receptors

    SciTech Connect (OSTI)

    Lin, David Yin-wei; Tanaka, Yoshimasa; Iwasaki, Masashi; Gittis, Apostolos G.; Su, Hua-Poo; Mikami, Bunzo; Okazaki, Taku; Honjo, Tasuku; Minato, Nagahiro; Garboczi, David N. (NIH); (Kyoto)

    2008-07-29

    Signaling through the programmed death 1 (PD-1) inhibitory receptor upon binding its ligand, PD-L1, suppresses immune responses against autoantigens and tumors and plays an important role in the maintenance of peripheral immune tolerance. Release from PD-1 inhibitory signaling revives 'exhausted' virus-specific T cells in chronic viral infections. Here we present the crystal structure of murine PD-1 in complex with human PD-L1. PD-1 and PD-L1 interact through the conserved front and side of their Ig variable (IgV) domains, as do the IgV domains of antibodies and T cell receptors. This places the loops at the ends of the IgV domains on the same side of the PD-1/PD-L1 complex, forming a surface that is similar to the antigen-binding surface of antibodies and T cell receptors. Mapping conserved residues allowed the identification of residues that are important in forming the PD-1/PD-L1 interface. Based on the structure, we show that some reported loss-of-binding mutations involve the PD-1/PD-L1 interaction but that others compromise protein folding. The PD-1/PD-L1 interaction described here may be blocked by antibodies or by designed small-molecule drugs to lower inhibitory signaling that results in a stronger immune response. The immune receptor-like loops offer a new surface for further study and potentially the design of molecules that would affect PD-1/PD-L1 complex formation and thereby modulate the immune response.

  16. Generation of mice deficient in RNA-binding motif protein 3 (RBM3) and characterization of its role in innate immune responses and cell growth

    SciTech Connect (OSTI)

    Matsuda, Atsushi [Department of Immunology, Graduate School of Medicine and Faculty of Medicine, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033 (Japan) [Department of Immunology, Graduate School of Medicine and Faculty of Medicine, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033 (Japan); Core Research for Evolution Science and Technology, Japan Science and Technology Agency, Chiyoda-ku, Tokyo 102-0075 (Japan); Ogawa, Masahiro [Laboratory of Immune Regulation, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871 (Japan)] [Laboratory of Immune Regulation, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871 (Japan); Yanai, Hideyuki [Department of Immunology, Graduate School of Medicine and Faculty of Medicine, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033 (Japan) [Department of Immunology, Graduate School of Medicine and Faculty of Medicine, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033 (Japan); Core Research for Evolution Science and Technology, Japan Science and Technology Agency, Chiyoda-ku, Tokyo 102-0075 (Japan); Naka, Daiji [ZOEGENE Corp., 1000 Kamoshida-cho, Aoba-ku, Yokohama, Kanagawa 227-0033 (Japan)] [ZOEGENE Corp., 1000 Kamoshida-cho, Aoba-ku, Yokohama, Kanagawa 227-0033 (Japan); Goto, Ayana; Ao, Tomoka [Department of Immunology, Graduate School of Medicine and Faculty of Medicine, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033 (Japan)] [Department of Immunology, Graduate School of Medicine and Faculty of Medicine, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033 (Japan); Tanno, Yuji [Laboratory of Chromosome Dynamics, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Yayoi, Bunkyo-ku, Tokyo 113-0032 (Japan)] [Laboratory of Chromosome Dynamics, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Yayoi, Bunkyo-ku, Tokyo 113-0032 (Japan); Takeda, Kiyoshi [Laboratory of Immune Regulation, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871 (Japan)] [Laboratory of Immune Regulation, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871 (Japan); Watanabe, Yoshinori [Laboratory of Chromosome Dynamics, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Yayoi, Bunkyo-ku, Tokyo 113-0032 (Japan)] [Laboratory of Chromosome Dynamics, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Yayoi, Bunkyo-ku, Tokyo 113-0032 (Japan); Honda, Kenya [Laboratory of Immune Regulation, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871 (Japan)] [Laboratory of Immune Regulation, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871 (Japan); Taniguchi, Tadatsugu, E-mail: tada@m.u-tokyo.ac.jp [Department of Immunology, Graduate School of Medicine and Faculty of Medicine, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033 (Japan) [Department of Immunology, Graduate School of Medicine and Faculty of Medicine, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033 (Japan); Core Research for Evolution Science and Technology, Japan Science and Technology Agency, Chiyoda-ku, Tokyo 102-0075 (Japan)

    2011-07-22

    Highlights: {yields} We identified RNA-binding motif protein 3 (RBM3) as CpG-B DNA-binding protein. {yields} RBM3 translocates from the nucleus to the cytoplasm and co-localized with CpG-B DNA. {yields} We newly generated Rbm3-deficient (Rbm3{sup -/-}) mice. {yields} DNA-mediated cytokine gene induction was normally occured in Rbm3{sup -/-} cells. {yields}Rbm3{sup -/-} MEFs showed poorer proliferation rate and increased number of G2-phase cells. -- Abstract: The activation of innate immune responses is critical to host defense against microbial infections, wherein nucleic acid-sensing pattern recognition receptors recognize DNA or RNA from viruses or bacteria and activate downstream signaling pathways. In a search for new DNA-sensing molecules that regulate innate immune responses, we identified RNA-binding motif protein 3 (RBM3), whose role has been implicated in the regulation of cell growth. In this study, we generated Rbm3-deficient (Rbm3{sup -/-}) mice to study the role of RBM3 in immune responses and cell growth. Despite evidence for its interaction with immunogenic DNA in a cell, no overt phenotypic abnormalities were found in cells from Rbm3{sup -/-} mice for the DNA-mediated induction of cytokine genes. Interestingly, however, Rbm3{sup -/-} mouse embryonic fibroblasts (MEFs) showed poorer proliferation rates as compared to control MEFs. Further cell cycle analysis revealed that Rbm3{sup -/-} MEFs have markedly increased number of G2-phase cells, suggesting a hitherto unknown role of RBM3 in the G2-phase control. Thus, these mutant mice and cells may provide new tools with which to study the mechanisms underlying the regulation of cell cycle and oncogenesis.

  17. Dispersion-correcting potentials can significantly improve the bond dissociation enthalpies and noncovalent binding energies predicted by density-functional theory

    SciTech Connect (OSTI)

    DiLabio, Gino A., E-mail: Gino.DiLabio@nrc.ca [National Institute for Nanotechnology, National Research Council of Canada, 11421 Saskatchewan Drive, Edmonton, Alberta T6G 2M9 (Canada); Department of Chemistry, University of British Columbia, Okanagan, 3333 University Way, Kelowna, British Columbia V1V 1V7 (Canada); Koleini, Mohammad [National Institute for Nanotechnology, National Research Council of Canada, 11421 Saskatchewan Drive, Edmonton, Alberta T6G 2M9 (Canada) [National Institute for Nanotechnology, National Research Council of Canada, 11421 Saskatchewan Drive, Edmonton, Alberta T6G 2M9 (Canada); Department of Chemical and Materials Engineering, University of Alberta, Edmonton, Alberta T6G 2V4 (Canada)

    2014-05-14

    Dispersion-correcting potentials (DCPs) are atom-centered Gaussian functions that are applied in a manner that is similar to effective core potentials. Previous work on DCPs has focussed on their use as a simple means of improving the ability of conventional density-functional theory methods to predict the binding energies of noncovalently bonded molecular dimers. We show in this work that DCPs developed for use with the LC-?PBE functional along with 6-31+G(2d,2p) basis sets are capable of simultaneously improving predicted noncovalent binding energies of van der Waals dimer complexes and covalent bond dissociation enthalpies in molecules. Specifically, the DCPs developed herein for the C, H, N, and O atoms provide binding energies for a set of 66 noncovalently bonded molecular dimers (the S66 set) with a mean absolute error (MAE) of 0.21 kcal/mol, which represents an improvement of more than a factor of 10 over unadorned LC-?PBE/6-31+G(2d,2p) and almost a factor of two improvement over LC-?PBE/6-31+G(2d,2p) used in conjunction with the D3 pairwise dispersion energy corrections. In addition, the DCPs reduce the MAE of calculated X-H and X-Y (X,Y = C, H, N, O) bond dissociation enthalpies for a set of 40 species from 3.2 kcal/mol obtained with unadorned LC-?PBE/6-31+G(2d,2p) to 1.6 kcal/mol. Our findings demonstrate that broad improvements to the performance of DFT methods may be achievable through the use of DCPs.

  18. The Structure of the MUR1 GDP-mannose 4,67-deydratase from A. thaliana: Implications for Ligand Binding Specificity

    SciTech Connect (OSTI)

    Mulichak, A.M.; Bonin, C.P.; Reiter, W.-D.; Garavito, R.M. (Michigan State University)

    2010-03-08

    GDP-D-mannose 4,6-dehydratase catalyzes the first step in the de novo synthesis of GDP-L-fucose, the activated form of L-fucose, which is a component of glycoconjugates in plants known to be important to the development and strength of stem tissues. We have determined the three-dimensional structure of the MUR1 dehydratase isoform from Arabidopsis thaliana complexed with its NADPH cofactor as well as with the ligands GDP and GDP-D-rhamnose. MUR1 is a member of the nucleoside-diphosphosugar modifying subclass of the short-chain dehydrogenase/reductase enzyme family, having homologous structures and a conserved catalytic triad of Lys, Tyr, and Ser/Thr residues. MUR1 is the first member of this subfamily to be observed as a tetramer, the interface of which reveals a close and intimate overlap of neighboring NADP{sup +}-binding sites. The GDP moiety of the substrate also binds in an unusual syn conformation. The protein-ligand interactions around the hexose moiety of the substrate support the importance of the conserved triad residues and an additional Glu side chain serving as a general base for catalysis. Phe and Arg side chains close to the hexose ring may serve to confer substrate specificity at the O2 position. In the MUR1/GDP-D-rhamnose complex, a single unique monomer within the protein tetramer that has an unoccupied substrate site highlights the conformational changes that accompany substrate binding and may suggest the existence of negative cooperativity in MUR1 function.

  19. COOH-terminal truncation of flightin decreases myofilament lattice organization, cross-bridge binding, and power output in Drosophila indirect flight muscle

    SciTech Connect (OSTI)

    Tanner, Bertrand C.W.; Miller, Mark S.; Miller, Becky M.; Lekkas, Panagiotis; Irving, Thomas C.; Maughan, David W.; Vigoreaux, Jim O. (IIT); (Vermont)

    2011-08-26

    The indirect flight muscle (IFM) of insects is characterized by a near crystalline myofilament lattice structure that likely evolved to achieve high power output. In Drosophila IFM, the myosin rod binding protein flightin plays a crucial role in thick filament organization and sarcomere integrity. Here we investigate the extent to which the COOH terminus of flightin contributes to IFM structure and mechanical performance using transgenic Drosophila expressing a truncated flightin lacking the 44 COOH-terminal amino acids (fln{sup {Delta}C44}). Electron microscopy and X-ray diffraction measurements show decreased myofilament lattice order in the fln{sup {Delta}C44} line compared with control, a transgenic flightin-null rescued line (fln{sup +}). fln{sup {Delta}C44} fibers produced roughly 1/3 the oscillatory work and power of fln{sup +}, with reduced frequencies of maximum work (123 Hz vs. 154 Hz) and power (139 Hz vs. 187 Hz) output, indicating slower myosin cycling kinetics. These reductions in work and power stem from a slower rate of cross-bridge recruitment and decreased cross-bridge binding in fln{sup {Delta}C44} fibers, although the mean duration of cross-bridge attachment was not different between both lines. The decreases in lattice order and myosin kinetics resulted in fln{sup {Delta}C44} flies being unable to beat their wings. These results indicate that the COOH terminus of flightin is necessary for normal myofilament lattice organization, thereby facilitating the cross-bridge binding required to achieve high power output for flight.

  20. Changes in the Zero-Point Energy of the Protons as the Source of the Binding Energy of Water to A-Phase DNA

    SciTech Connect (OSTI)

    Reiter, G. F.; Senesi, R.; Mayers, J.

    2010-10-01

    The measured changes in the zero-point kinetic energy of the protons are entirely responsible for the binding energy of water molecules to A phase DNA at the concentration of 6 water molecules/base pair. The changes in kinetic energy can be expected to be a significant contribution to the energy balance in intracellular biological processes and the properties of nano-confined water. The shape of the momentum distribution in the dehydrated A phase is consistent with coherent delocalization of some of the protons in a double well potential, with a separation of the wells of 0.2 Angst .

  1. NS1-binding protein abrogates the elevation of cell viability by the influenza A virus NS1 protein in association with CRKL

    SciTech Connect (OSTI)

    Miyazaki, Masaya [Department of Cancer Pathology, Hokkaido University Graduate School of Medicine, N15W7, Kita-ku, Sapporo 060-8638 (Japan)] [Department of Cancer Pathology, Hokkaido University Graduate School of Medicine, N15W7, Kita-ku, Sapporo 060-8638 (Japan); Nishihara, Hiroshi, E-mail: hnishihara@med.hokudai.ac.jp [Department of Translational Pathology, Hokkaido University Graduate School of Medicine, N15W7, Kita-ku, Sapporo 060-8638 (Japan)] [Department of Translational Pathology, Hokkaido University Graduate School of Medicine, N15W7, Kita-ku, Sapporo 060-8638 (Japan); Hasegawa, Hideki [Department of Pathology, National Institute of Infectious Diseases, Sinjuku-ku, Tokyo (Japan)] [Department of Pathology, National Institute of Infectious Diseases, Sinjuku-ku, Tokyo (Japan); Tashiro, Masato [Influenza Virus Research Center, National Institute of Infectious Diseases, Sinjuku-ku, Tokyo (Japan)] [Influenza Virus Research Center, National Institute of Infectious Diseases, Sinjuku-ku, Tokyo (Japan); Wang, Lei [Department of Translational Pathology, Hokkaido University Graduate School of Medicine, N15W7, Kita-ku, Sapporo 060-8638 (Japan)] [Department of Translational Pathology, Hokkaido University Graduate School of Medicine, N15W7, Kita-ku, Sapporo 060-8638 (Japan); Kimura, Taichi; Tanino, Mishie; Tsuda, Masumi [Department of Cancer Pathology, Hokkaido University Graduate School of Medicine, N15W7, Kita-ku, Sapporo 060-8638 (Japan)] [Department of Cancer Pathology, Hokkaido University Graduate School of Medicine, N15W7, Kita-ku, Sapporo 060-8638 (Japan); Tanaka, Shinya [Department of Cancer Pathology, Hokkaido University Graduate School of Medicine, N15W7, Kita-ku, Sapporo 060-8638 (Japan) [Department of Cancer Pathology, Hokkaido University Graduate School of Medicine, N15W7, Kita-ku, Sapporo 060-8638 (Japan); Department of Translational Pathology, Hokkaido University Graduate School of Medicine, N15W7, Kita-ku, Sapporo 060-8638 (Japan)

    2013-11-29

    Highlights: NS1 induced excessive phosphorylation of ERK and elevated cell viability. NS1-BP expression and CRKL knockdown abolished survival effect of NS1. NS1-BP and NS1 formed the complex through the interaction with CRKL-SH3(N). -- Abstract: The influenza A virus non-structural protein 1 (NS1) is a multifunctional virulence factor consisting of an RNA binding domain and several Src-homology (SH) 2 and SH3 binding motifs, which promotes virus replication in the host cell and helps to evade antiviral immunity. NS1 modulates general host cell physiology in association with various cellular molecules including NS1-binding protein (NS1-BP) and signaling adapter protein CRK-like (CRKL), while the physiological role of NS1-BP during influenza A virus infection especially in association with NS1 remains unclear. In this study, we analyzed the intracellular association of NS1-BP, NS1 and CRKL to elucidate the physiological roles of these molecules in the host cell. In HEK293T cells, enforced expression of NS1 of A/Beijing (H1N1) and A/Indonesia (H5N1) significantly induced excessive phosphorylation of ERK and elevated cell viability, while the over-expression of NS1-BP and the abrogation of CRKL using siRNA abolished such survival effect of NS1. The pull-down assay using GST-fusion CRKL revealed the formation of intracellular complexes of NS1-BP, NS1 and CRKL. In addition, we identified that the N-terminus SH3 domain of CRKL was essential for binding to NS1-BP using GST-fusion CRKL-truncate mutants. This is the first report to elucidate the novel function of NS1-BP collaborating with viral protein NS1 in modulation of host cell physiology. In addition, an alternative role of adaptor protein CRKL in association with NS1 and NS1-BP during influenza A virus infection is demonstrated.

  2. Peptide binding characteristics of the non-classical class Ib MHC molecule HLA-E assessed by a recombinant random peptide approach

    E-Print Network [OSTI]

    Stevens, James; Joly, Etienne; Trowsdale, John; Butcher, Geoffrey W

    2001-06-20

    with resuspension buffer and then solubilized by resuspending and mixing for 1 hour at room temperature in 8 M urea, 0.1 M NaH 2 PO 4 , 0.01 M Tris-HCl; pH 8.0 (buffer A; pH 8.0). The mixtures were then centrifuged (25,000 g) to re- move any insoluble material. Urea... and Receptor Binding Assays. In: Combinatorial Peptide and Nonpeptide Libraries-A Handbook for the Search of Lead Structures. Edited by Jung G. pp. Weinheim, FRG: Verlag Chemie; 1996203-246 30. Garboczi DN, Hung DT, Wiley DC: HLA-A2-peptide complexes...

  3. The binding characteristics and orientation of a novel radioligand with distinct properties at 5-HT3A and 5-HT3AB receptors

    E-Print Network [OSTI]

    Thompson, Andrew J.; Verheij, Mark H. P.; Verbeek, Joost; Windhorst, Albert D.; de Esch, Iwan J. P.; Lummis, Sarah C. R.

    2014-04-28

    constant (koff). kon can also be calculated as described by Hill (Hill, 1909), where koff is predetermined from radioligand dissociation rate experiments. on off k kK ?d koff kon y = Bmin + Bmax - Bmin1+10[L ]- log IC50 7 (Equ. 5) 2... , Dougherty DA (2002). Cation-pi Interactions in Ligand Recognition by Serotonergic (5-HT3A) and Nicotinic Acetylcholine Receptors: The Anomalous Binding Properties of Nicotine. Biochemistry 41: 10262-10269. Billen B, Spurny R, Brams M, van Elk R, Valera...

  4. The Escherichia coli RhaS Transcriptional Activator: Transcriptional Activation by the DNA-Binding Domain, The Interdomain Effector Response, and Negative Autoregulation

    E-Print Network [OSTI]

    Skredenske, Jeffrey M.

    2012-05-31

    : The AraC/XylS family activator RhaS negatively 78 autoregulates rhaSR expression by preventing cyclic AMP receptor protein activation 1 CHAPTER 1 Transcription Activation by the DNA-Binding Domain of the AraC Family Protein Rha... encodes a second L-rhamnose responsive transcription activator, RhaR (37). RhaR activates transcription of the operon that encodes the two activator proteins, rhaSR (37, 38). All three operons in the L-rhamnose regulon also require a second activator...

  5. Mutational analysis of the RNA-binding domain of the Prunus necrotic ringspot virus (PNRSV) movement protein reveals its requirement for cell-to-cell movement

    SciTech Connect (OSTI)

    Carmen Herranz, Ma [Instituto de Biologia Molecular y Celular de Plantas (IBMCP), UPV-CSIC, Avda. de los Naranjos, s/n, 46022, Valencia (Spain); Sanchez-Navarro, Jesus-Angel [Instituto de Biologia Molecular y Celular de Plantas (IBMCP), UPV-CSIC, Avda. de los Naranjos, s/n, 46022, Valencia (Spain); Sauri, Ana [Departament de Bioquimica i Biologia Molecular, Universitat de Valencia, E-46100 Burjassot (Spain); Mingarro, Ismael [Departament de Bioquimica i Biologia Molecular, Universitat de Valencia, E-46100 Burjassot (Spain); Pallas, Vicente [Instituto de Biologia Molecular y Celular de Plantas (IBMCP), UPV-CSIC, Avda. de los Naranjos, s/n, 46022, Valencia (Spain)]. E-mail: vpallas@ibmcp.upv.es

    2005-08-15

    The movement protein (MP) of Prunus necrotic ringspot virus (PNRSV) is required for cell-to-cell movement. MP subcellular localization studies using a GFP fusion protein revealed highly punctate structures between neighboring cells, believed to represent plasmodesmata. Deletion of the RNA-binding domain (RBD) of PNRSV MP abolishes the cell-to-cell movement. A mutational analysis on this RBD was performed in order to identify in vivo the features that govern viral transport. Loss of positive charges prevented the cell-to-cell movement even though all mutants showed a similar accumulation level in protoplasts to those observed with the wild-type (wt) MP. Synthetic peptides representing the mutants and wild-type RBDs were used to study RNA-binding affinities by EMSA assays being approximately 20-fold lower in the mutants. Circular dichroism analyses revealed that the secondary structure of the peptides was not significantly affected by mutations. The involvement of the affinity changes between the viral RNA and the MP in the viral cell-to-cell movement is discussed.

  6. Shedding Light on the EOS-Gravity Degeneracy and Constraining the Nuclear Symmetry Energy from the Gravitational Binding Energy of Neutron Stars

    E-Print Network [OSTI]

    Xiao-Tao He; F. J. Fattoyev; Bao-An Li; W. G. Newton

    2015-10-14

    A thorough understanding of properties of neutron stars requires both a reliable knowledge of the equation of state (EOS) of super-dense nuclear matter and the strong-field gravity theories simultaneously. To provide information that may help break this EOS-gravity degeneracy, we investigate effects of nuclear symmetry energy on the gravitational binding energy of neutron stars within GR and the scalar-tensor subset of alternative gravity models. We focus on effects of the slope $L$ of nuclear symmetry energy at saturation density and the high-density behavior of nuclear symmetry energy. We find that the variation of either the density slope $L$ or the high-density behavior of nuclear symmetry energy leads to large changes in the binding energy of neutron stars. The difference in predictions using the GR and the scalar-tensor theory appears only for massive neutron stars, and even then is significantly smaller than the difference resulting from variations in the symmetry energy.

  7. Water on BN doped benzene: A hard test for exchange-correlation functionals and the impact of exact exchange on weak binding

    SciTech Connect (OSTI)

    Al-Hamdani, Yasmine S.; Alf, Dario; von Lilienfeld, O. Anatole; Michaelides, Angelos

    2014-10-22

    Density functional theory (DFT) studies of weakly interacting complexes have recently focused on the importance of van der Waals dispersion forces, whereas the role of exchange has received far less attention. Here, by exploiting the subtle binding between water and a boron and nitrogen doped benzene derivative (1,2-azaborine) we show how exact exchange can alter the binding conformation within a complex. Benchmark values have been calculated for three orientations of the water monomer on 1,2-azaborine from explicitly correlated quantum chemical methods, and we have also used diffusion quantum Monte Carlo. For a host of popular DFT exchange-correlation functionals we show that the lack of exact exchange leads to the wrong lowest energy orientation of water on 1,2-azaborine. As such, we suggest that a high proportion of exact exchange and the associated improvement in the electronic structure could be needed for the accurate prediction of physisorption sites on doped surfaces and in complex organic molecules. Meanwhile to predict correct absolute interaction energies an accurate description of exchange needs to be augmented by dispersion inclusive functionals, and certain non-local van der Waals functionals (optB88- and optB86b-vdW) perform very well for absolute interaction energies. Through a comparison with water on benzene and borazine (B?N?H?) we show that these results could have implications for the interaction of water with doped graphene surfaces, and suggest a possible way of tuning the interaction energy.

  8. Crystal Structures of Apo and Metal-Bound Forms of the UreE Protein from Helicobacter pylori: Role of Multiple Metal Binding Sites

    SciTech Connect (OSTI)

    Shi, Rong; Munger, Christine; Asinas, Abdalin; Benoit, Stephane L.; Miller, Erica; Matte, Allan; Maier, Robert J.; Cygler, Miroslaw (McGill); (Georgia); (Biotech Res.)

    2010-10-22

    The crystal structure of the urease maturation protein UreE from Helicobacter pylori has been determined in its apo form at 2.1 {angstrom} resolution, bound to Cu{sup 2+} at 2.7 {angstrom} resolution, and bound to Ni{sup 2+} at 3.1 {angstrom} resolution. Apo UreE forms dimers, while the metal-bound enzymes are arranged as tetramers that consist of a dimer of dimers associated around the metal ion through coordination by His102 residues from each subunit of the tetramer. Comparison of independent subunits from different crystal forms indicates changes in the relative arrangement of the N- and C-terminal domains in response to metal binding. The improved ability of engineered versions of UreE containing hexahistidine sequences at either the N-terminal or C-terminal end to provide Ni{sup 2+} for the final metal sink (urease) is eliminated in the H102A version. Therefore, the ability of the improved Ni{sup 2+}-binding versions to deliver more nickel is likely an effect of an increased local concentration of metal ions that can rapidly replenish transferred ions bound to His102.

  9. Pathogenicity of the BRCA1 Missense Variant M1775K is Determined by the Disruption of the BRCT Phosphopeptide-Binding Pocket: a Multi-Modal Approach

    SciTech Connect (OSTI)

    Tischkowitz,M.; Hamel, N.; Carvalho, M.; Birrane, G.; Soni, A.; van Beers, E.; Joosse, S.; Wong, N.; Novak, D.; et al

    2008-01-01

    A number of germ-line mutations in the BRCA1 gene confer susceptibility to breast and ovarian cancer. However, it remains difficult to determine whether many single amino-acid (missense) changes in the BRCA1 protein that are frequently detected in the clinical setting are pathologic or not. Here, we used a combination of functional, crystallographic, biophysical, molecular and evolutionary techniques, and classical genetic segregation analysis to demonstrate that the BRCA1 missense variant M1775K is pathogenic. Functional assays in yeast and mammalian cells showed that the BRCA1 BRCT domains carrying the amino-acid change M1775K displayed markedly reduced transcriptional activity, indicating that this variant represents a deleterious mutation. Importantly, the M1775K mutation disrupted the phosphopeptide-binding pocket of the BRCA1 BRCT domains, thereby inhibiting the BRCA1 interaction with the proteins BRIP1 and CtIP, which are involved in DNA damage-induced checkpoint control. These results indicate that the integrity of the BRCT phosphopeptide-binding pocket is critical for the tumor suppression function of BRCA1. Moreover, this study demonstrates that multiple lines of evidence obtained from a combination of functional, structural, molecular and evolutionary techniques, and classical genetic segregation analysis are required to confirm the pathogenicity of rare variants of disease-susceptibility genes and obtain important insights into the underlying pathogenetic mechanisms.

  10. Shedding Light on the EOS-Gravity Degeneracy and Constraining the Nuclear Symmetry Energy from the Gravitational Binding Energy of Neutron Stars

    E-Print Network [OSTI]

    He, Xiao-Tao; Li, Bao-An; Newton, W G

    2015-01-01

    A thorough understanding of properties of neutron stars requires both a reliable knowledge of the equation of state (EOS) of super-dense nuclear matter and the strong-field gravity theories simultaneously. To provide information that may help break this EOS-gravity degeneracy, we investigate effects of nuclear symmetry energy on the gravitational binding energy of neutron stars within GR and the scalar-tensor subset of alternative gravity models. We focus on effects of the slope $L$ of nuclear symmetry energy at saturation density and the high-density behavior of nuclear symmetry energy. We find that the variation of either the density slope $L$ or the high-density behavior of nuclear symmetry energy leads to large changes in the binding energy of neutron stars. The difference in predictions using the GR and the scalar-tensor theory appears only for massive neutron stars, and even then is significantly smaller than the difference resulting from variations in the symmetry energy.

  11. Structural dynamics and ssDNA binding activity of the three N-terminal domains of the large subunit of Replication Protein A from small angle X-ray scattering

    SciTech Connect (OSTI)

    Pretto, Dalyir I.; Tsutakawa, Susan; Brosey, Chris A.; Castillo, Amalchi; Chagot, Marie-Eve; Smith, Jarrod A.; Tainer, John A.; Chazin, Walter J.

    2010-03-11

    Replication Protein A (RPA) is the primary eukaryotic ssDNA binding protein utilized in diverse DNA transactions in the cell. RPA is a heterotrimeric protein with seven globular domains connected by flexible linkers, which enable substantial inter-domain motion that is essential to its function. Small angle X-ray scattering (SAXS) experiments on two multi-domain constructs from the N-terminus of the large subunit (RPA70) were used to examine the structural dynamics of these domains and their response to the binding of ssDNA. The SAXS data combined with molecular dynamics simulations reveal substantial interdomain flexibility for both RPA70AB (the tandem high affinity ssDNA binding domains A and B connected by a 10-residue linker) and RPA70NAB (RPA70AB extended by a 70-residue linker to the RPA70N protein interaction domain). Binding of ssDNA to RPA70NAB reduces the interdomain flexibility between the A and B domains, but has no effect on RPA70N. These studies provide the first direct measurements of changes in orientation of these three RPA domains upon binding ssDNA. The results support a model in which RPA70N remains structurally independent of RPA70AB in the DNA bound state and therefore freely available to serve as a protein recruitment module.

  12. Water on BN doped benzene: A hard test for exchange-correlation functionals and the impact of exact exchange on weak binding

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Al-Hamdani, Yasmine S.; Alf, Dario; von Lilienfeld, O. Anatole; Michaelides, Angelos

    2014-10-22

    Density functional theory (DFT) studies of weakly interacting complexes have recently focused on the importance of van der Waals dispersion forces, whereas the role of exchange has received far less attention. Here, by exploiting the subtle binding between water and a boron and nitrogen doped benzene derivative (1,2-azaborine) we show how exact exchange can alter the binding conformation within a complex. Benchmark values have been calculated for three orientations of the water monomer on 1,2-azaborine from explicitly correlated quantum chemical methods, and we have also used diffusion quantum Monte Carlo. For a host of popular DFT exchange-correlation functionals we showmorethat the lack of exact exchange leads to the wrong lowest energy orientation of water on 1,2-azaborine. As such, we suggest that a high proportion of exact exchange and the associated improvement in the electronic structure could be needed for the accurate prediction of physisorption sites on doped surfaces and in complex organic molecules. Meanwhile to predict correct absolute interaction energies an accurate description of exchange needs to be augmented by dispersion inclusive functionals, and certain non-local van der Waals functionals (optB88- and optB86b-vdW) perform very well for absolute interaction energies. Through a comparison with water on benzene and borazine (B?N?H?) we show that these results could have implications for the interaction of water with doped graphene surfaces, and suggest a possible way of tuning the interaction energy.less

  13. Water on BN doped benzene: A hard test for exchange-correlation functionals and the impact of exact exchange on weak binding

    SciTech Connect (OSTI)

    Al-Hamdani, Yasmine S.; Michaelides, Angelos; Alf, Dario; Lilienfeld, O. Anatole von

    2014-11-14

    Density functional theory (DFT) studies of weakly interacting complexes have recently focused on the importance of van der Waals dispersion forces, whereas the role of exchange has received far less attention. Here, by exploiting the subtle binding between water and a boron and nitrogen doped benzene derivative (1,2-azaborine) we show how exact exchange can alter the binding conformation within a complex. Benchmark values have been calculated for three orientations of the water monomer on 1,2-azaborine from explicitly correlated quantum chemical methods, and we have also used diffusion quantum Monte Carlo. For a host of popular DFT exchange-correlation functionals we show that the lack of exact exchange leads to the wrong lowest energy orientation of water on 1,2-azaborine. As such, we suggest that a high proportion of exact exchange and the associated improvement in the electronic structure could be needed for the accurate prediction of physisorption sites on doped surfaces and in complex organic molecules. Meanwhile to predict correct absolute interaction energies an accurate description of exchange needs to be augmented by dispersion inclusive functionals, and certain non-local van der Waals functionals (optB88- and optB86b-vdW) perform very well for absolute interaction energies. Through a comparison with water on benzene and borazine (B{sub 3}N{sub 3}H{sub 6}) we show that these results could have implications for the interaction of water with doped graphene surfaces, and suggest a possible way of tuning the interaction energy.

  14. Structural Insights into Membrane Targeting by the Flagellar Calcium-binding Protein (FCaBP) a Myristoylated and Palmitoylated Calcium Sensor in Trypanosoma cruzi

    SciTech Connect (OSTI)

    J Wingard; J Ladner; M Vanarotti; A Fisher; H Robinson; K Buchanan; D Engman; J Ames

    2011-12-31

    The flagellar calcium-binding protein (FCaBP) of the protozoan Trypanosoma cruzi is targeted to the flagellar membrane where it regulates flagellar function and assembly. As a first step toward understanding the Ca{sup 2+}-induced conformational changes important for membrane-targeting, we report here the x-ray crystal structure of FCaBP in the Ca{sup 2+}-free state determined at 2.2{angstrom} resolution. The first 17 residues from the N terminus appear unstructured and solvent-exposed. Residues implicated in membrane targeting (Lys-19, Lys-22, and Lys-25) are flanked by an exposed N-terminal helix (residues 26-37), forming a patch of positive charge on the protein surface that may interact electrostatically with flagellar membrane targets. The four EF-hands in FCaBP each adopt a 'closed conformation' similar to that seen in Ca{sup 2+}-free calmodulin. The overall fold of FCaBP is closest to that of grancalcin and other members of the penta EF-hand superfamily. Unlike the dimeric penta EF-hand proteins, FCaBP lacks a fifth EF-hand and is monomeric. The unstructured N-terminal region of FCaBP suggests that its covalently attached myristoyl group at the N terminus may be solvent-exposed, in contrast to the highly sequestered myristoyl group seen in recoverin and GCAP1. NMR analysis demonstrates that the myristoyl group attached to FCaBP is indeed solvent-exposed in both the Ca{sup 2+}-free and Ca{sup 2+}-bound states, and myristoylation has no effect on protein structure and folding stability. We propose that exposed acyl groups at the N terminus may anchor FCaBP to the flagellar membrane and that Ca{sup 2+}-induced conformational changes may control its binding to membrane-bound protein targets..

  15. Regulation of insulin-like growth factor binding protein-4 in Ah responsive and Ah nonresponsive human breast cancer cells by 17 B-estradiol and 2,3,7,8 tetrachlorodibenzo-p-dioxin

    E-Print Network [OSTI]

    Schrope, Katherine Eillene

    1997-01-01

    This study focused on the effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on insulin-like growth factor binding protein-4 (IGFBP-4) protein secretion and MRNA expression. In human breast cancer cells, 17 O-estradiol (E2) induced IGFBP-4...

  16. Unveiling N-Protonation and Anion-Binding Effects on Fe/N/C Catalysts for O2 Reduction in Proton-Exchange-Membrane Fuel Cells

    SciTech Connect (OSTI)

    J Herranz; F Jaouen; M Lefevre; U Kramm; E Proietti; J Dodelet; P Bogdanoff; S Fiechter; I Abs-Wurbach; et al.

    2011-12-31

    The high cost of proton-exchange-membrane fuel cells would be considerably reduced if platinum-based catalysts were replaced by iron-based substitutes, which have recently demonstrated comparable activity for oxygen reduction but whose cause of activity decay in acidic medium has been elusive. Here, we reveal that the activity of Fe/N/C catalysts prepared through a pyrolysis in NH{sub 3} is mostly imparted by acid-resistant FeN{sub 4} sites whose turnover frequency for the O{sub 2} reduction can be regulated by fine chemical changes of the catalyst surface. We show that surface N-groups protonate at pH 1 and subsequently bind anions. This results in decreased activity for the O{sub 2} reduction. The anions can be removed chemically or thermally, which restores the activity of acid-resistant FeN{sub 4} sites. These results are interpreted as an increased turnover frequency of FeN{sub 4} sites when specific surface N-groups protonate. These unprecedented findings provide a new perspective for stabilizing the most active Fe/N/C catalysts known to date.

  17. Cell-penetrating DNA-binding protein as a safe and efficient naked DNA delivery carrier in vitro and in vivo

    SciTech Connect (OSTI)

    Kim, Eun-Sung; Yang, Seung-Woo; Hong, Dong-Ki; Kim, Woo-Taek; Kim, Ho-Guen; Lee, Sang-Kyou

    2010-01-29

    Non-viral gene delivery is a safe and suitable alternative to viral vector-mediated delivery to overcome the immunogenicity and tumorigenesis associated with viral vectors. Using the novel, human-origin Hph-1 protein transduction domain that can facilitate the transduction of protein into cells, we developed a new strategy to deliver naked DNA in vitro and in vivo. The new DNA delivery system contains Hph-1-GAL4 DNA-binding domain (DBD) fusion protein and enhanced green fluorescent protein (EGFP) reporter plasmid that includes the five repeats of GAL4 upstream activating sequence (UAS). Hph-1-GAL4-DBD protein formed complex with plasmid DNA through the specific interaction between GAL4-DBD and UAS, and delivered into the cells via the Hph-1-PTD. The pEGFP DNA was successfully delivered by the Hph-1-GAL4 system, and the EGFP was effectively expressed in mammalian cells such as HeLa and Jurkat, as well as in Bright Yellow-2 (BY-2) plant cells. When 10 {mu}g of pEGFP DNA was intranasally administered to mice using Hph-1-GAL4 protein, a high level of EGFP expression was detected throughout the lung tissue for 7 days. These results suggest that an Hph-1-PTD-mediated DNA delivery strategy may be an useful non-viral DNA delivery system for gene therapy and DNA vaccines.

  18. Liquid drops on a surface: using density functional theory to calculate the binding potential and drop profiles and comparing with results from mesoscopic modelling

    E-Print Network [OSTI]

    Adam P. Hughes; Uwe Thiele; Andrew J. Archer

    2015-01-28

    The contribution to the free energy for a film of liquid of thickness $h$ on a solid surface, due to the interactions between the solid-liquid and liquid-gas interfaces is given by the binding potential, $g(h)$. The precise form of $g(h)$ determines whether or not the liquid wets the surface. Note that differentiating $g(h)$ gives the Derjaguin or disjoining pressure. We develop a microscopic density functional theory (DFT) based method for calculating $g(h)$, allowing us to relate the form of $g(h)$ to the nature of the molecular interactions in the system. We present results based on using a simple lattice gas model, to demonstrate the procedure. In order to describe the static and dynamic behaviour of non-uniform liquid films and drops on surfaces, a mesoscopic free energy based on $g(h)$ is often used. We calculate such equilibrium film height profiles and also directly calculate using DFT the corresponding density profiles for liquid drops on surfaces. Comparing quantities such as the contact angle and also the shape of the drops, we find good agreement between the two methods. We also study in detail the effect on $g(h)$ of truncating the range of the dispersion forces, both those between the fluid molecules and those between the fluid and wall. We find that truncating can have a significant effect on $g(h)$ and the associated wetting behaviour of the fluid.

  19. Coordinate regulation/localization of the carbohydrate responsive binding protein (ChREBP) by two nuclear export signal sites: Discovery of a new leucine-rich nuclear export signal site

    SciTech Connect (OSTI)

    Fukasawa, Masashi; Ge, Qing; Wynn, R. Max; Ishii, Seiji [Biochemistry Department, University of Texas Southwestern Medical Center, Dallas, TX 75390-9038 (United States)] [Biochemistry Department, University of Texas Southwestern Medical Center, Dallas, TX 75390-9038 (United States); Uyeda, Kosaku, E-mail: Kosaku.Uyeda@utsouthwestern.edu [Biochemistry Department, University of Texas Southwestern Medical Center, Dallas, TX 75390-9038 (United States) [Biochemistry Department, University of Texas Southwestern Medical Center, Dallas, TX 75390-9038 (United States); Dallas Veterans Affairs Medical Center, Dallas, TX 75216 (United States)

    2010-01-08

    Carbohydrate response element binding protein (ChREBP) is responsible for conversion of dietary carbohydrate to storage fat in liver by coordinating expression of the enzymes that channel glycolytic pyruvate into lipogenesis. The activation of ChREBP in response to high glucose is nuclear localization and transcription, and the inactivation of ChREBP under low glucose involves export from the nucleus to the cytosol. Here we report a new nuclear export signal site ('NES1') of ChREBP. Together these signals provide ChREBP with two NES sequences, both the previously reported NES2 and now the new NES1 coordinate to interact together with CRM1 (exportin) for nuclear export of the carbohydrate response element binding protein.

  20. Binding energies of the ground triplet state a{sup 3}?{sub u}{sup +} of Rb{sub 2} and Cs{sub 2} in terms of the generalized Le RoyBernstein near-dissociation expansion

    SciTech Connect (OSTI)

    Sovkov, V. B.; Ivanov, V. S. [V.A. Fock Institute of Physics and Department of Physics of St. Petersburg State University, Ulyanovskaya Street 1, Petrodvoretz, St. Petersburg 198504 (Russian Federation)] [V.A. Fock Institute of Physics and Department of Physics of St. Petersburg State University, Ulyanovskaya Street 1, Petrodvoretz, St. Petersburg 198504 (Russian Federation)

    2014-04-07

    Formulae of Le RoyBernstein near-dissociation theory are derived in a general isotopeinvariant form, applicable to any term in the rotational expansion of a diatomic ro-vibrational term value. It is proposed to use the generalized Le RoyBernstein expansion to describe the binding energies (ro-vibrational term values) of the ground triplet state a{sup 3}?{sub u}{sup +} of alkali metal dimers. The parameters of this description are determined for Rb{sub 2} and Cs{sub 2} molecules. This approach gives a recipe to calculate the whole variety of the binding energies with characteristic accuracies from ?1 10{sup ?3} to 1 10{sup ?2} cm{sup ?1} using a relatively simple algebraic equation.

  1. Binding and Direct Electrochemistry of OmcA, an Outer-Membrane Cytochrome from an Iron Reducing Bacterium, with Oxide Electrodes: A Candidate Biofuel Cell System

    SciTech Connect (OSTI)

    Eggleston, Carrick M.; Voros, Janos; Shi, Liang; Lower, Brian H.; Droubay, Timothy C.; Colberg, Patricia J.

    2008-02-15

    Dissimilatory iron-reducing bacteria transfer electrons to solid ferric respiratory electron acceptors. Outer-membrane cytochromes expressed by these organisms are of interest in both microbial fuel cells and biofuel cells. We use optical waveguide lightmode spectroscopy (OWLS) to show that OmcA, an 85 kDa decaheme outer-membrane c-type cytochrome from Shewanella oneidensis MR-1, adsorbs to isostructural Al2O3 and Fe2O3 in similar amounts. Adsorption is ionic-strength and pH dependent (peak adsorption at pH 6.57.0). The thickness of the OmcA layer on Al2O3 at pH 7.0 [5.8 1.1 (2r) nm] from OWLS is similar, within error, to that observed using atomic force microscopy (4.8 2 nm). The highest adsorption density observed was 334 ng cm 2 (2.4 1012 molecules cm 2), corresponding to a monolayer or 9.9 nm diameter spheres or submonolayer coverage by smaller molecules. Direct electrochemistry of OmcA on Fe2O3 electrodes was observed using cyclic voltammetry, with cathodic peak potentials of 380 to 320 mV versus Ag/AgCl. Variations in the cathodic peak positions are speculatively attributed to redox-linked conformation change or changes in molecular orientation. OmcA can exchange electrons with ITO electrodes at higher current densities than with Fe2O3. Overall, OmcA can bind to and exchange electrons with several oxides, and thus its utility in fuel cells is not restricted to Fe2O3.

  2. Impact of the [delta]F508 Mutation in First Nucleotide-binding Domain of Human Cystic Fibrosis Transmembrane Conductance Regulator on Domain Folding and Structure

    SciTech Connect (OSTI)

    Lewis, Hal A.; Zhao, Xun; Wang, Chi; Sauder, J. Michael; Rooney, Isabelle; Noland, Brian W.; Lorimer, Don; Kearins, Margaret C.; Conners, Kris; Condon, Brad; Maloney, Peter C.; Guggino, William B.; Hunt, John F.; Emtage, Spencer (SG); (Columbia); (JHU)

    2010-07-19

    Cystic fibrosis is caused by defects in the cystic fibrosis transmembrane conductance regulator (CFTR), commonly the deletion of residue Phe-508 (DeltaF508) in the first nucleotide-binding domain (NBD1), which results in a severe reduction in the population of functional channels at the epithelial cell surface. Previous studies employing incomplete NBD1 domains have attributed this to aberrant folding of DeltaF508 NBD1. We report structural and biophysical studies on complete human NBD1 domains, which fail to demonstrate significant changes of in vitro stability or folding kinetics in the presence or absence of the DeltaF508 mutation. Crystal structures show minimal changes in protein conformation but substantial changes in local surface topography at the site of the mutation, which is located in the region of NBD1 believed to interact with the first membrane spanning domain of CFTR. These results raise the possibility that the primary effect of DeltaF508 is a disruption of proper interdomain interactions at this site in CFTR rather than interference with the folding of NBD1. Interestingly, increases in the stability of NBD1 constructs are observed upon introduction of second-site mutations that suppress the trafficking defect caused by the DeltaF508 mutation, suggesting that these suppressors might function indirectly by improving the folding efficiency of NBD1 in the context of the full-length protein. The human NBD1 structures also solidify the understanding of CFTR regulation by showing that its two protein segments that can be phosphorylated both adopt multiple conformations that modulate access to the ATPase active site and functional interdomain interfaces.

  3. How Dynein Binds to Microtubules

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    organelles, in a directional fashion along microtubules that serve as cellular conveyor belts. Consistent with this central role, cytoplasmic dynein is associated with a number of...

  4. Folding and binding Editorial overview

    E-Print Network [OSTI]

    is on the study of how protein folding, unfolding and aggregation reactions commence, and on the study of California, Berkeley. Her lab focuses on studies of protein folding and dynamics. Currently shebased kinetics. Much of the progress that has been made in the past fifty years in the study of protein folding

  5. How Dynein Binds to Microtubules

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    AFDC Printable Version Share this resource Send a link to EERE: Alternative Fuels Data Center Home Page to someone by E-mail Share EERE: Alternative Fuels Data Center Home Page on Facebook Tweet about EERE: Alternative Fuels Data Center Home Page on Twitter Bookmark EERE: Alternative Fuels Data Center Homesum_a_epg0_fpd_mmcf_m.xls" ,"Available from WebQuantity ofkandz-cm11 Outreach Home Room NewsInformation CurrentHenry Bellamy, Ph.D.Food Drive HolidayHours UsedFire 1GetHow Do IDoes

  6. How Dynein Binds to Microtubules

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    AFDC Printable Version Share this resource Send a link to EERE: Alternative Fuels Data Center Home Page to someone by E-mail Share EERE: Alternative Fuels Data Center Home Page on Facebook Tweet about EERE: Alternative Fuels Data Center Home Page on Twitter Bookmark EERE: Alternative Fuels Data Center Homesum_a_epg0_fpd_mmcf_m.xls" ,"Available from WebQuantityBonneville Power Administration would likeUniverse (JournalvivoHigh energyHighlandWorkshop-Summer 2014toHow Do I WorkDo

  7. How Dynein Binds to Microtubules

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    AFDC Printable Version Share this resource Send a link to EERE: Alternative Fuels Data Center Home Page to someone by E-mail Share EERE: Alternative Fuels Data Center Home Page on Facebook Tweet about EERE: Alternative Fuels Data Center Home Page on Twitter Bookmark EERE: Alternative Fuels Data Center Homesum_a_epg0_fpd_mmcf_m.xls" ,"Available from WebQuantityBonneville Power Administration would likeUniverse (JournalvivoHigh energyHighlandWorkshop-Summer 2014toHow Do I WorkDoHow

  8. How Dynein Binds to Microtubules

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    AFDC Printable Version Share this resource Send a link to EERE: Alternative Fuels Data Center Home Page to someone by E-mail Share EERE: Alternative Fuels Data Center Home Page on Facebook Tweet about EERE: Alternative Fuels Data Center Home Page on Twitter Bookmark EERE: Alternative Fuels Data Center Homesum_a_epg0_fpd_mmcf_m.xls" ,"Available from WebQuantityBonneville Power Administration would likeUniverse (JournalvivoHigh energyHighlandWorkshop-Summer 2014toHow Do I WorkDoHowHow

  9. How Dynein Binds to Microtubules

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    AFDC Printable Version Share this resource Send a link to EERE: Alternative Fuels Data Center Home Page to someone by E-mail Share EERE: Alternative Fuels Data Center Home Page on Facebook Tweet about EERE: Alternative Fuels Data Center Home Page on Twitter Bookmark EERE: Alternative Fuels Data Center Homesum_a_epg0_fpd_mmcf_m.xls" ,"Available from WebQuantityBonneville Power Administration would likeUniverse (JournalvivoHigh energyHighlandWorkshop-Summer 2014toHow Do I WorkDoHowHowHow

  10. How Dynein Binds to Microtubules

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    AFDC Printable Version Share this resource Send a link to EERE: Alternative Fuels Data Center Home Page to someone by E-mail Share EERE: Alternative Fuels Data Center Home Page on Facebook Tweet about EERE: Alternative Fuels Data Center Home Page on Twitter Bookmark EERE: Alternative Fuels Data Center Homesum_a_epg0_fpd_mmcf_m.xls" ,"Available from WebQuantityBonneville Power Administration would likeUniverse (JournalvivoHigh energyHighlandWorkshop-Summer 2014toHow Do I

  11. The anti-tumor effect of cross-reacting material 197, an inhibitor of heparin-binding EGF-like growth factor, in human resistant ovarian cancer

    SciTech Connect (OSTI)

    Tang, Xiao-han; Deng, Suo; Li, Meng; Lu, Mei-song

    2012-06-15

    Highlights: Black-Right-Pointing-Pointer HB-EGF over-expression in A2780/Taxol, A2780/CDDP cells and the matched xenografts. Black-Right-Pointing-Pointer CRM197 induces enhanced apoptosis in A2780/Taxol and A2780/CDDP cells. Black-Right-Pointing-Pointer CRM197 arrests A2780/Taxol and A2780/CDDP cells at G0/G1 phase. Black-Right-Pointing-Pointer CRM197 suppressed the A2780/Taxol and A2780/CDDP growth of xenografts. -- Abstract: Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a promising target for ovarian cancer therapy. Cross-reacting material 197 (CRM197), a specific HB-EGF inhibitor, has been proven to represent possible chemotherapeutic agent for ovarian cancer. However, the effect of CRM197 on the resistant ovarian carcinoma cells has not been sufficiently elucidated. Here, we found that HB-EGF was over-expressed in a paclitaxel-resistant human ovarian carcinoma cell line (A2780/Taxol) and a cisplatin-resistant cell line (A2780/CDDP), as well as the xenograft mouse tissue samples with these cells. To investigate the possible significance of the HB-EGF over-expression in A2780/Taxol and A2780/CDDP cells, we inhibited HB-EGF expression by CRM197 to investigate the effect of CRM197 treatment on these cells. We observed that CRM197 significantly induced anti-proliferative activity in a dose-dependent manner with the cell-cycle arrest at the G0/G1 phase and enhanced apoptosis in A2780/Taxol and A2780/CDDP cells. The sensitive ovarian carcinoma parental cell line (A2780), A2780/Taxol and A2780/CDDP cells formed tumors in nude mice, and enhanced tumorigenicity was observed in drug-resistant tumors. Furthermore, we observed that CRM197 significantly suppressed the growth of drug-resistant ovarian cancer xenografts in vivo (p < 0.001). These results suggest that CRM197 as an HB-EGF-targeted agent has potent anti-tumor activity in paclitaxel- and cisplatin-resistant ovarian cancer which over-express HB-EGF.

  12. Structural Insights into the Functional Role of the Hcn Sub-domain of the Receptor-Binding Domain of the Botulinum Neurotoxin Mosaic Serotype C/D

    SciTech Connect (OSTI)

    Zhang, Yanfeng; Gardberg, Anna; Edwards, Tom E.; Sankaran, Banumathi; Robinson, Howard; Varnum, Susan M.; Buchko, Garry W.

    2013-07-01

    Botulinum neurotoxin (BoNT), the causative agent of the deadly neuroparalytic disease botulism, is the most poisonous protein known for humans. Produced by different strains of the anaerobic bacterium Clostridium botulinum, BoNT effects cellular intoxication via a multistep mechanism executed by the three modules of the activated protein. Endocytosis, the first step of cellular intoxication, is triggered by the ~50 kDa, heavy-chain receptor-binding module (HCR) that is specific for a ganglioside and a protein receptor on neuronal cell surfaces. This dual receptor recognition mechanism between BoNT and the host cells membrane is well documented and occurs via specific intermolecular interactions with the C-terminal sub-domain, Hcc, of BoNT-HCR. The N-terminal sub-domain of BoNT-HCR, Hcn, comprises ~50% of BoNT-HCR and adopts a B-sheet jelly roll fold. While suspected in assisting cell surface recognition, no unambiguous function for the Hcn sub-domain in BoNT has been indentified. To obtain insights into the potential function of the Hcn sub-domain in BoNT, the first crystal structure of a BoNT with an organic ligand bound to the Hcn sub-domain has been obtained. Here, we describe the crystal structure of BoNT/CD-HCR determined at 1.70 resolution with a tetraethylene glycol (PG4) molecule bound in an hydrophobic cleft between B-strands in the B-sheet jelly fold roll of the Hcn sub-domain. The molecule is completely engulfed in the cleft, making numerous hydrophobic (Y932, S959, W966, and D1042) and hydrophilic (S935, W977, L979, N1013, and I1066) contacts with the proteins side chain and backbone that may mimic in vivo interactions with the phospholipid membranes on neuronal cell surfaces. A sulfate ion was also observed bound to residues T1176, D1177, K1196, and R1243 in the Hcc sub-domain of BoNT/CD-HCR. In the crystal structure of a similar protein, BoNT/D-HCR, a sialic acid

  13. Low p53 Binding Protein 1 (53BP1) Expression Is Associated With Increased Local Recurrence in Breast Cancer Patients Treated With Breast-Conserving Surgery and Radiotherapy

    SciTech Connect (OSTI)

    Neboori, Hanmanth J.R.; Haffty, Bruce G.; Wu Hao; Yang Qifeng; Aly, Amal; Goyal, Sharad; Schiff, Devora; Moran, Meena S.; Golhar, Ryan; Chen Chunxia; Moore, Dirk; and others

    2012-08-01

    Purpose: To investigate whether the expression of p53 binding protein 1 (53BP1) has prognostic significance in a cohort of early-stage breast cancer patients treated with breast-conserving surgery and radiotherapy (BCS+RT). Methods and Materials: A tissue microarray of early-stage breast cancer treated with BCS+RT from a cohort of 514 women was assayed for 53BP1, estrogen receptor, progesterone receptor, and HER2 expression by immunohistochemistry. Through log-rank tests and univariate and multivariate models, the staining profile of each tumor was correlated with clinical endpoints, including ipsilateral breast recurrence-free survival (IBRFS), distant metastasis-free survival (DMFS), cause-specific survival (CSS), recurrence-free survival (RFS), and overall survival (OS). Results: Of the 477 (93%) evaluable tumors, 63 (13%) were scored as low. Low expression of 53BP1 was associated with worse outcomes for all endpoints studied, including 10-year IBRFS (76.8% vs. 90.5%; P=.01), OS (66.4% vs. 81.7%; P=.02), CSS (66.0% vs. 87.4%; P<.01), DMFS (55.9% vs. 87.0%; P<.01), and RFS (45.2% vs. 80.6%; P<.01). Multivariate analysis incorporating various clinico-pathologic markers and 53BP1 expression found that 53BP1 expression was again an independent predictor of all endpoints (IBRFS: P=.0254; OS: P=.0094; CSS: P=.0033; DMFS: P=.0006; RFS: P=.0002). Low 53BP1 expression was also found to correlate with triple-negative (TN) phenotype (P<.01). Furthermore, in subset analysis of all TN breast cancer, negative 53BP1 expression trended for lower IBRFS (72.3% vs. 93.9%; P=.0361) and was significant for worse DMFS (48.2% vs. 86.8%; P=.0035) and RFS (37.8% vs. 83.7%; P=.0014). Conclusion: Our data indicate that low 53BP1 expression is an independent prognostic indicator for local relapse among other endpoints in early-stage breast cancer and TN breast cancer patients treated with BCS+RT. These results should be verified in larger cohorts of patients to validate their clinical significance.

  14. A Cysteine-Rich CCG Domain Contains a Novel [4Fe-4S] Cluster Binding Motif As Deduced From Studies With Subunit B of Heterodisulfide Reductase From Methanothermobacter Marburgensis

    SciTech Connect (OSTI)

    Hamann, N.; Mander, G.J.; Shokes, J.E.; Scott, R.A.; Bennati, M.; Hedderich, R.

    2009-06-01

    Heterodisulfide reductase (HDR) of methanogenic archaea with its active-site [4Fe-4S] cluster catalyzes the reversible reduction of the heterodisulfide (CoM-S-S-CoB) of the methanogenic coenzyme M (CoM-SH) and coenzyme B (CoB-SH). CoM-HDR, a mechanistic-based paramagnetic intermediate generated upon half-reaction of the oxidized enzyme with CoM-SH, is a novel type of [4Fe-4S]{sup 3+} cluster with CoM-SH as a ligand. Subunit HdrB of the Methanothermobacter marburgensis HdrABC holoenzyme contains two cysteine-rich sequence motifs (CX{sub 31-39}CCX{sub 35-36}CXXC), designated as CCG domain in the Pfam database and conserved in many proteins. Here we present experimental evidence that the C-terminal CCG domain of HdrB binds this unusual [4Fe-4S] cluster. HdrB was produced in Escherichia coli, and an iron-sulfur cluster was subsequently inserted by in vitro reconstitution. In the oxidized state the cluster without the substrate exhibited a rhombic EPR signal (g{sub zyx} = 2.015, 1.995, and 1.950) reminiscent of the CoM-HDR signal. {sup 57}Fe ENDOR spectroscopy revealed that this paramagnetic species is a [4Fe-4S] cluster with {sup 57}Fe hyperfine couplings very similar to that of CoM-HDR. CoM-{sup 33}SH resulted in a broadening of the EPR signal, and upon addition of CoM-SH the midpoint potential of the cluster was shifted to values observed for CoM-HDR, both indicating binding of CoM-SH to the cluster. Site-directed mutagenesis of all 12 cysteine residues in HdrB identified four cysteines of the C-terminal CCG domain as cluster ligands. Combined with the previous detection of CoM-HDR-like EPR signals in other CCG domain-containing proteins our data indicate a general role of the C-terminal CCG domain in coordination of this novel [4Fe-4S] cluster. In addition, Zn K-edge X-ray absorption spectroscopy identified an isolated Zn site with an S{sub 3}(O/N){sub 1} geometry in HdrB and the HDR holoenzyme. The N-terminal CCG domain is suggested to provide ligands to the Zn site.

  15. A density functional tight binding/force field approach to the interaction of molecules with rare gas clusters: Application to (C{sub 6}H{sub 6}){sup +/0}Ar{sub n} clusters

    SciTech Connect (OSTI)

    Iftner, Christophe; Simon, Aude; Korchagina, Kseniia; Rapacioli, Mathias; Spiegelman, Fernand

    2014-01-21

    We propose in the present paper a SCC-DFTB/FF (Self-Consistent-Charge Density Functional based Tight Binding/Force-Field) scheme adapted to the investigation of molecules trapped in rare gas environments. With respect to usual FF descriptions, the model involves the interaction of quantum electrons in a molecule with rare gas atoms in an anisotropic scheme. It includes polarization and dispersion contributions and can be used for both neutral and charged species. Parameters for this model are determined for hydrocarbon-argon complexes and the model is validated for small hydrocarbons. With the future aim of studying polycyclic aromatic hydrocarbons in Ar matrices, extensive benchmark calculations are performed on (C{sub 6}H{sub 6}){sup +/0}Ar{sub n} clusters against DFT and CCSD(T) calculations for the smaller sizes, and more generally against other experimental and theoretical data. Results on the structures and energetics (isomer ordering and energy separation, cohesion energy per Ar atom) are presented in detail for n = 18, 13, 20, 27, and 30, for both neutrals and cations. We confirm that the clustering of Ar atoms leads to a monotonous decrease of the ionization potential of benzene for n ? 20, in line with previous experimental and FF data.

  16. In the absence of cellular poly (A) binding protein, the glycolytic enzyme GAPDH translocated to the cell nucleus and activated the GAPDH mediated apoptotic pathway by enhancing acetylation and serine 46 phosphorylation of p53

    SciTech Connect (OSTI)

    Thangima Zannat, Mst.; Bhattacharjee, Rumpa B.; Bag, Jnanankur

    2011-06-03

    Highlights: {yields} PABP knock down and cell apoptosis. {yields} Nuclear translocation of GAPDH in PABP depleted cells. {yields} Role of p53 in apoptosis of PABP depleted cells. {yields} Bax translocation and cytochrome C release and caspase 3 activation following PABP depletion. {yields} Association of p53 with Bcl2 and Bax. -- Abstract: The cytoplasmic poly (A) binding protein (PABP) interacts with 3' poly (A) tract of eukaryotic mRNA and is important for both translation and stability of mRNA. Previously, we have shown that depletion of PABP by siRNA prevents protein synthesis and consequently leads to cell death through apoptosis. In the present investigation, we studied the mechanism of cell apoptosis. We show that in the absence of PABP, the glycolytic enzyme GAPDH translocated to the cell nucleus and activated the GAPDH mediated apoptotic pathway by enhancing acetylation and serine 46 phosphorylation of p53. As a result, p53 translocated to the mitochondria to initiate Bax mediated apoptosis.

  17. Structural analysis of a novel rabbit monoclonal antibody R53 targeting an epitope in HIV-1 gp120 C4 region critical for receptor and co-receptor binding

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Pan, Ruimin; Chen, Yuxin; Vaine, Michael; Hu, Guangnan; Wang, Shixia; Lu, Shan; Kong, Xiang -Peng

    2015-07-15

    The fourth conserved region (C4) in the HIV-1 envelope glycoprotein (Env) gp120 is a structural element that is important for its function, as it binds to both the receptor CD4 and the co-receptor CCR5/CXCR4. It has long been known that this region is highly immunogenic and that it harbors B-cell as well as T-cell epitopes. It is the target of a number of antibodies in animal studies, which are called CD4-blockers. However, the mechanism by which the virus shields itself from such antibody responses is not known. Here, we determined the crystal structure of R53 in complex with its epitopemorepeptide using a novel anti-C4 rabbit monoclonal antibody R53. Our data show that although the epitope of R53 covers a highly conserved sequence 433AMYAPPI439, it is not available in the gp120 trimer and in the CD4-bound conformation. Our results suggest a masking mechanism to explain how HIV-1 protects this critical region from the human immune system.less

  18. Examining Management Issues for Incidentally Caught Species in Highly Migratory Species Fisheries in the Western and Central Pacific Ocean

    E-Print Network [OSTI]

    Chan, Valerie Ann

    2014-01-01

    dynamics in the central Pacific Ocean, 1952- 1998. II. Afishing for tunas in the Pacific Ocean. Ecology and Societywestern and central north Pacific Ocean. ISC. 2013a. Stock

  19. Radionuclide-binding compound, a radionuclide delivery system, a method of making a radium complexing compound, a method of extracting a radionuclide, and a method of delivering a radionuclide

    DOE Patents [OSTI]

    Fisher, Darrell R. (Richland, WA); Wai, Chien M. (Moscow, ID); Chen, Xiaoyuan (Moscow, ID)

    2000-01-01

    The invention pertains to compounds which specifically bind radionuclides, and to methods of making radionuclide complexing compounds. In one aspect, the invention includes a radionuclide delivery system comprising: a) a calix[n]arene-crown-[m]-ether compound, wherein n is an integer greater than 3, and wherein m is an integer greater than 3, the calix[n]arene-crown-[m]-ether compound comprising at least two ionizable groups; and b) an antibody attached to the calix[n]arene-crown-[m]-ether compound. In another aspect, the invention includes a method of making a radium complexing compound, comprising: a) providing a calix[n]arene compound, wherein n is an integer greater than 3, the calix[n]arene compound comprising n phenolic hydroxyl groups; b) providing a crown ether precursor, the crown ether precursor comprising a pair of tosylated ends; c) reacting the pair of tosylated ends with a pair of the phenolic hydroxyl groups to convert said pair of phenolic hydroxyl groups to ether linkages, the ether linkages connecting the crown ether precursor to the calix[n]arene to form a calix[n]arene-crown-[m]-ether compound, wherein m is an integer greater than 3; d) converting remaining phenolic hydroxyl groups to esters; e) converting the esters to acids, the acids being proximate a crown-[m]-ether portion of the calix[n]arene-crown-[m]-ether compound; and f) providing a Ra.sup.2+ ion within the crown-[m]-ether portion of the calix[n]arene-crown-[m]-ether compound.

  20. Heparin sensing: Blue-chip binding

    E-Print Network [OSTI]

    Shriver, Zachary H.

    Heparin is an anionic polysaccharide that has tremendous clinical importance as an anticoagulant. Several dyes have been developed that can detect heparin, and the latest example named Mallard Blue has now been shown ...

  1. Maxwell's demon for calcium binding to calmodulin?

    E-Print Network [OSTI]

    S. L. Mironov

    2013-05-14

    In the recent paper (2011) Faas and co-workers claimed that calmodulin could directly detect Ca2+ signals by acting as extremely fast calcium buffer. However the results and their interpretation raise serious doubts about this conclusion.

  2. Analysis of Holliday junction-binding compounds

    E-Print Network [OSTI]

    Rideout, Marc Christoffer

    2011-01-01

    of antibiotic resistance in bacteria, viral life-cycles, andof multiple drug resistance in bacteria, we have been

  3. Testing of Vibration Damping Binding Systems

    E-Print Network [OSTI]

    Causey, Gregory C.

    .............................................................................................. 43 5.1.5 Program to Download Data from the Spectrum Analyzer ............................................. 43 5.1.6 Conversion Program used to Setup the Spectrum Analyzer Output for Graphing...... 44 5.1.7 Program to Convert the Spectrum Analyzer Output to G's........................................... 45 5

  4. Experimental pitfalls in protein binding measurements

    E-Print Network [OSTI]

    Schmidt, S.; Derendorf, H.

    2006-10-27

    1e+2 1e+3 1e+4 1e+5 1e+6 1e+7 1e+8 1e+9 1e+10 control with albumin control without albumin 0.25 x MIC 0.5 x MIC 1 x MIC 2 x MIC 4 x MIC 8 x MIC 1 6 xMIC 2.421.084.322.25h 0.0190.0220.0460.033EC50 [#2;#29; g/mL] 1.9117.541.871.90#2;#21; [h-1...

  5. Confinement induced binding of noble gas atoms

    SciTech Connect (OSTI)

    Khatua, Munmun; Pan, Sudip; Chattaraj, Pratim K., E-mail: pkc@chem.iitkgp.ernet.in [Department of Chemistry and Centre for Theoretical Studies, Indian Institute of Technology, Kharagpur 721302 (India)

    2014-04-28

    The stability of Ng{sub n}@B{sub 12}N{sub 12} and Ng{sub n}@B{sub 16}N{sub 16} systems is assessed through a density functional study and ab initio simulation. Although they are found to be thermodynamically unstable with respect to the dissociation of individual Ng atoms and parent cages, ab initio simulation reveals that except Ne{sub 2}@B{sub 12}N{sub 12} they are kinetically stable to retain their structures intact throughout the simulation time (500 fs) at 298 K. The Ne{sub 2}@B{sub 12}N{sub 12} cage dissociates and the Ne atoms get separated as the simulation proceeds at this temperature but at a lower temperature (77 K) it is also found to be kinetically stable. He-He unit undergoes translation, rotation and vibration inside the cavity of B{sub 12}N{sub 12} and B{sub 16}N{sub 16} cages. Electron density analysis shows that the He-He interaction in He{sub 2}@B{sub 16}N{sub 16} is of closed-shell type whereas for the same in He{sub 2}@B{sub 12}N{sub 12} there may have some degree of covalent character. In few cases, especially for the heavier Ng atoms, the Ng-N/B bonds are also found to have some degree of covalent character. But the Wiberg bond indices show zero bond order in He-He bond and very low bond order in cases of Ng-N/B bonds. The energy decomposition analysis further shows that the ?E{sub orb} term contributes 40.9% and 37.3% towards the total attraction in the He{sub 2} dimers having the same distances as in He{sub 2}@B{sub 12}N{sub 12} and He{sub 2}@B{sub 16}N{sub 16}, respectively. Therefore, confinement causes some type of orbital interaction between two He atoms, which akins to some degree of covalent character.

  6. Method of identity analyte-binding peptides

    DOE Patents [OSTI]

    Kauvar, L.M.

    1990-10-16

    A method for affinity chromatography or adsorption of a designated analyte utilizes a paralog as the affinity partner. The immobilized paralog can be used in purification or analysis of the analyte; the paralog can also be used as a substitute for antibody in an immunoassay. The paralog is identified by screening candidate peptide sequences of 4--20 amino acids for specific affinity to the analyte. 5 figs.

  7. Structural Study of Lipid-binding Proteins

    E-Print Network [OSTI]

    Tsai, Han-Chun

    2013-08-09

    . ....................................................................... 156 Figure 4.12 A mushroom-like cavity at the center of potential receptor-recognition surface ....................................................................................................... 158 x LIST OF TABLES...

  8. Binding Organic Liquids - Energy Innovation Portal

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    AFDC Printable Version Share this resource Send a link to EERE: Alternative Fuels Data Center Home Page to someone by E-mail Share EERE: Alternative Fuels Data Center Home Page on Facebook Tweet about EERE: Alternative Fuels Data Center Home Page on Twitter Bookmark EERE: Alternative Fuels Data Center Homesum_a_epg0_fpd_mmcf_m.xls" ,"Available from WebQuantity ofkandz-cm11 OutreachProductswsicloudwsiclouddenDVA N C E D B L O OLaura|Bilayer Graphene Gets aVehicles and Fuels Vehicles and

  9. Nicotinamide mononucleotide adenylyltransferase displays alternate binding

    Office of Scientific and Technical Information (OSTI)

    AFDC Printable Version Share this resource Send a link to EERE: Alternative Fuels Data Center Home Page to someone by E-mail Share EERE: Alternative Fuels Data Center Home Page on Facebook Tweet about EERE: Alternative Fuels Data Center Home Page on Twitter Bookmark EERE: Alternative Fuels Data Center Homesum_a_epg0_fpd_mmcf_m.xls" ,"Available from WebQuantity of NaturalDukeWakefieldSulfateSciTech Connect Nanomechanical switch for| SciTechPhaseNewton's Method(Conference)modes for

  10. Fields of Education and Training

    E-Print Network [OSTI]

    Hasrc, Vasf

    ISCED 97 contains 25 two-digit fields of education. The classification presented here uses a three-digit SWEDEN December 1999 #12;2 Contents Page Introduction 3 Structure and Rationale of the Classification 5 Relation to other classifications and ISCED 97 dimensions 10 Iinter-disciplinary and broad programmes 12

  11. Synergistic Anion and Metal Binding to the Ferric Ion-binding Protein from Neisseria gonorrhoeae

    E-Print Network [OSTI]

    Guo, Maolin; Harvey, Ian; Yang, Weiping; Coghill, Lorraine; Campopiano, Dominic J; Parkinson, John A; MacGillivray, Ross T A; Harris, Wesley R; Sadler, Peter J

    2003-10-07

    The 34-kDa periplasmic iron-transport protein (FBP) from Neisseria gonorrhoeae (nFBP) contains Fe(III) and (hydrogen)phosphate (synergistic anion). It has a characteristic ligand-to-metal charge-transfer absorption band ...

  12. High Resolution Genome Wide Binding Event Finding and Motif Discovery Reveals Transcription Factor Spatial Binding Constraints

    E-Print Network [OSTI]

    Guo, Yuchun

    An essential component of genome function is the syntax of genomic regulatory elements that determine how diverse transcription factors interact to orchestrate a program of regulatory control. A precise characterization ...

  13. Relating metal binding to DNA binding in the nickel regulatory protein NikR

    E-Print Network [OSTI]

    Phillips, Christine M. (Christine Marie)

    2010-01-01

    The concentration of transition metals within the cell must be tightly regulated. If the concentration of a given transition metal is too low the cell may not be able to perform life-sustaining processes, while high levels ...

  14. Mutant ATP-binding RNA Aptamers Reveal the Structural Basis for Ligand Binding

    E-Print Network [OSTI]

    Heller, Eric

    loop residues and the stems (Figure 2). The stacking of the ®rst stem is continued by the G7ÁG11 and G8-like arrangement (G8, A9, A10 and AMP). The second stem continues into the internal loop via the G17ÁG30 base its amino group and N1 to G8 and via its N3 to A12. Another important interaction involves the 2H

  15. DNA binding specificity of the p73 DNA-binding domain

    E-Print Network [OSTI]

    Tse, Pui Wah

    2011-01-01

    of DNA recognition by p53 tetramers. Mol Cell 22, 741-753.site as a self-assembled tetramer. Structure 18, 246- Chene,structure of a p53 core tetramer bound to DNA. Oncogene 28,

  16. Investigation of Transcription Factor Binding Sequences and Target Genes using Protein Binding Microarrays

    E-Print Network [OSTI]

    Bolotin, Eugene Leonidovich

    2010-01-01

    64] A. J. Watt, W. D. Garrison, and S. A. Duncan. HNF4: aBattle, K. Si-Tayeb, W. Garrison, S. Chhinder, J. Li, R. J.43, [40] A. J. Watt, W. D. Garrison, and S. A. Duncan. HNF4:

  17. Triplet Acetylenes as Synthetic Equivalents of 1,2-Bicarbenes: Phantom n,* State Controls Reactivity in

    E-Print Network [OSTI]

    Alabugin, Igor

    [3.3.0.02,8 .04,6 ]octanes (homoquadricyclanes). In the case of pyrazinyl acetylenes, the primary acetylene: PET). Dramatically enhanced ISC between -* S1 state and "phantom" n,* triplet excited state

  18. Student Trainee (Accounting)

    Broader source: Energy.gov [DOE]

    The Department of Energy (DOE), Office of Science (SC), Integrated Support Center - Chicago (ISC-CH), Office of the Chief Financial Officer (CR) Pathways Internship is designed to provide students...

  19. Preparing for Cori

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    who are developing highly performant HPC applications for the Xeon Phi. Visit their web site at http:ixpug.org. IXPUG at ISC15 IXPUG is hosting a BoF and Workshop on...

  20. Urban Influences on Stream Chemistry and Biology in the Big Brushy Creek Watershed, South Carolina

    E-Print Network [OSTI]

    , and buildings). As ISC increases in urban areas, the infiltration of precipitation into soils Water Air Soil under baseflow conditions (Hoare, 1984; Smart, Jones, & Sebaugh, 1985; Wahl, McKellar, & Williams, 1997