National Library of Energy BETA

Sample records for u-098 isc bind

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

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

    ISC BIND RUNTIMECHECK Error Lets Remote Users Deny Service Against Recursive Resolvers V-172: ISC BIND RUNTIMECHECK Error Lets Remote Users Deny Service Against Recursive...

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

    Broader source: Energy.gov [DOE]

    A remote server can cause the target connected client to crash. Organizations across the Internet are reporting crashes interrupting service on BIND 9 nameservers performing recursive queries. Affected servers crash after logging an error in query.c with the following message: "INSIST(! dns_rdataset_isassociated(sigrdataset))" Multiple versions are reported as being affected, including all currently supported release versions of ISC BIND 9. ISC is actively investigating the root cause and working to produce patches which avoid the crash.

  3. U-183: ISC BIND DNS Resource Records Handling Vulnerability

    Broader source: Energy.gov [DOE]

    This problem was uncovered while testing with experimental DNS record types. It is possible to add records to BIND with null (zero length) rdata fields.

  4. V-172: ISC BIND RUNTIME_CHECK Error Lets Remote Users Deny Service Against Recursive Resolvers

    Broader source: Energy.gov [DOE]

    A defect exists which allows an attacker to crash a BIND 9 recursive resolver with a RUNTIME_CHECK error in resolver.c

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

    Broader source: Energy.gov [DOE]

    A defect in the affected BIND 9 versions allows an attacker to remotely cause the "named" process to exit using a specially crafted packet. This defect affects both recursive and authoritative servers. The code location of the defect makes it impossible to protect BIND using ACLs configured within named.conf or by disabling any features at compile-time or run-time. A remote attacker would need to be able to send a specially crafted packet directly to a server running a vulnerable version of BIND. There is also the potential for an indirect attack via malware that is inadvertently installed and run, where infected machines have direct access to an organization's nameservers.

  6. IXPUG ISC15 Documents

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

    Training » IXPUG ISC15 Documents IXPUG ISC15 Documents Sort by: Default | Name | Date (low-high) | Date (high-low) | Source | Category BoF: IXPUG ISC15 BoF Introduction July 15, 2015 | Author(s): Thomas Steinke, ZIB | Download File: 1Welcome.pdf | pdf | 98 KB Workshop: Intel® Xeon Phi(tm) Processor "Knights Landing" Architectural Overview Author(s): Avinash Sodani, Senior Principal Engineer, Intel Corporation Chief Architect, Knights Landing Processor | Download File:

  7. IXPUG ISC15 Documents

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

    Luigi Iapichino | Download File: 2bISC15-BoF-Preconditioning.pdf | pdf | 1.2 MB Workshop: Language Impact on Vectorization: Vector Programming in CC++ July 16, 2015 | Author(s):...

  8. IXPUG ISC15 Documents

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

    Processor | Download File: KNL-ISC-2015-Workshop-Keynote.pdf | pdf | 1 MB Workshop: Language Impact on Vectorization: Vector Programming in CC++ July 16, 2015 | Author(s):...

  9. IXPUG ISC15 Documents

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

    Intel® Xeon Phi(tm) Processor "Knights Landing" Architectural Overview Author(s): Avinash Sodani, Senior Principal Engineer, Intel Corporation Chief Architect, Knights Landing Processor | Download File: KNL-ISC-2015-Workshop-Keynote.pdf | pdf | 1 MB BoF: IXPUG ISC15 BoF Introduction July 15, 2015 | Author(s): Thomas Steinke, ZIB | Download File: 1Welcome.pdf | pdf | 98 KB BoF: Performance Optimization of OpenFOAM on Xeon/Xeon Phi July 15, 2015 | Author(s): Nishant Agrawal | Download

  10. IXPUG ISC15 Documents

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

    Language Impact on Vectorization: Vector Programming in C/C++ July 16, 2015 | Author(s): Guilherme Amadio | Download File: Language-Impact-on-Vectorization-Vector-Programming-in-C++.pdf | pdf | 924 KB Workshop: Coding for the Future:Knights Landing and beyond July 16, 2015 | Author(s): CJ Newburn, Intel SW/HW HPC Architect, .Community Builder | Download File: Preparing-Software-for-KNL-ISC15-IXPUG-Keynote.pdf | pdf | 1.1 MB Workshop: Performance Optimization of OpenFOAM on Xeon/Xeon Phi July 16,

  11. IXPUG ISC15 Documents

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

    Vectorization Efficiency Metrics July 16, 2015 | Author(s): Zakhar A. Matveev, CJ Newburn | Download File: Vectorization-Efficiency-Metrics.pdf | pdf | 319 KB Workshop: Coding for the Future:Knights Landing and beyond July 16, 2015 | Author(s): CJ Newburn, Intel SW/HW HPC Architect, .Community Builder | Download File: Preparing-Software-for-KNL-ISC15-IXPUG-Keynote.pdf | pdf | 1.1 MB Workshop: Improving node-level performance in Gadget: data structure and data locality July 16, 2015 | Author(s):

  12. IXPUG ISC15 Documents

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

    Workshop: Language Impact on Vectorization: Vector Programming in C/C++ July 16, 2015 | Author(s): Guilherme Amadio | Download File: Language-Impact-on-Vectorization-Vector-Programming-in-C++.pdf | pdf | 924 KB Workshop: Coding for the Future:Knights Landing and beyond July 16, 2015 | Author(s): CJ Newburn, Intel SW/HW HPC Architect, .Community Builder | Download File: Preparing-Software-for-KNL-ISC15-IXPUG-Keynote.pdf | pdf | 1.1 MB Workshop: Performance Optimization of OpenFOAM on Xeon/Xeon

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

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

    Statements (EIS) | U.S. DOE Office of Science (SC) Office Environmental Assessments (EA) / Environmental Impact Statements (EIS) Integrated Support Center (ISC) ISC Home About Services Freedom of Information Act (FOIA) Privacy Act NEPA Documents ISC-Chicago Office Categorical Exclusion Determinations ISC-Oak Ridge Office Categorical Exclusion Determinations ISC-Chicago Office Environmental Assessments and Environmental Impact Statements ISC-Oak Ridge Office Environmental Assessments and

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

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

    Statements (EIS) | U.S. DOE Office of Science (SC) Environmental Assessments (EA) / Environmental Impact Statements (EIS) Integrated Support Center (ISC) ISC Home About Services Freedom of Information Act (FOIA) Privacy Act NEPA Documents ISC-Chicago Office Categorical Exclusion Determinations ISC-Oak Ridge Office Categorical Exclusion Determinations ISC-Chicago Office Environmental Assessments and Environmental Impact Statements ISC-Oak Ridge Office Environmental Assessments and

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

    Open Energy Info (EERE)

    Sustainable Communities (ISC) Address: 535 Stone Cutters Way Montpelier, Vermont 05602 USA Place: Montpelier, Vermont Zip: 05602 Website: www.iscvt.org References: http:...

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

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

    Office of Science (SC) Office Categorical Exclusion (CX) Determinations Integrated Support Center (ISC) ISC Home About Services Freedom of Information Act (FOIA) Privacy Act NEPA Documents ISC-Chicago Office Categorical Exclusion Determinations ISC-Oak Ridge Office Categorical Exclusion Determinations ISC-Chicago Office Environmental Assessments and Environmental Impact Statements ISC-Oak Ridge Office Environmental Assessments and Environmental Impact Statements Contact Information

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

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

    Office of Science (SC) Categorical Exclusion (CX) Determinations Integrated Support Center (ISC) ISC Home About Services Freedom of Information Act (FOIA) Privacy Act NEPA Documents ISC-Chicago Office Categorical Exclusion Determinations ISC-Oak Ridge Office Categorical Exclusion Determinations ISC-Chicago Office Environmental Assessments and Environmental Impact Statements ISC-Oak Ridge Office Environmental Assessments and Environmental Impact Statements Contact Information Integrated

  18. 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)

    About » Field Offices » ISC Home Integrated Support Center (ISC) ISC Home About Services Freedom of Information Act (FOIA) Privacy Act NEPA Documents Contact Information Integrated Support Center Roxanne Purucker U.S. Department of Energy 9800 S. Cass Avenue Argonne, IL 60439 P: (630) 252-2110 Don F. Thress, Jr. U.S. Department of Energy 200 Administration Road Oak Ridge, TN 37830 P: (865) 576-4444 Integrated Support Center The Office of Science Integrated Support Center proudly facilitates

  19. Quantifying and Reducing Curve-Fitting Uncertainty in Isc: Preprint

    SciTech Connect (OSTI)

    Campanelli, Mark; Duck, Benjamin; Emery, Keith

    2015-09-28

    Current-voltage (I-V) curve measurements of photovoltaic (PV) devices are used to determine performance parameters and to establish traceable calibration chains. Measurement standards specify localized curve fitting methods, e.g., straight-line interpolation/extrapolation of the I-V curve points near short-circuit current, Isc. By considering such fits as statistical linear regressions, uncertainties in the performance parameters are readily quantified. However, the legitimacy of such a computed uncertainty requires that the model be a valid (local) representation of the I-V curve and that the noise be sufficiently well characterized. Using more data points often has the advantage of lowering the uncertainty. However, more data points can make the uncertainty in the fit arbitrarily small, and this fit uncertainty misses the dominant residual uncertainty due to so-called model discrepancy. Using objective Bayesian linear regression for straight-line fits for Isc, we investigate an evidence-based method to automatically choose data windows of I-V points with reduced model discrepancy. We also investigate noise effects. Uncertainties, aligned with the Guide to the Expression of Uncertainty in Measurement (GUM), are quantified throughout.

  20. U-038: BIND 9 Resolver crashes after logging an error in query.c

    Broader source: Energy.gov [DOE]

    A remote server can cause the target connected client to crash. Organizations across the Internet are reporting crashes interrupting service on BIND 9 nameservers performing recursive queries. Affected servers crash after logging an error in query.c with the following message: "INSIST(! dns_rdataset_isassociated(sigrdataset))" Multiple versions are reported as being affected, including all currently supported release versions of ISC BIND 9. ISC is actively investigating the root cause and working to produce patches which avoid the crash.

  1. V-007: McAfee Firewall Enterprise ISC BIND Record Handling Lockup Vulnerability

    Broader source: Energy.gov [DOE]

    McAfee has acknowledged a vulnerability in McAfee Firewall Enterprise, which can be exploited by malicious people to cause a DoS (Denial of Service).

  2. Jackie Chen to give keynote address at ISC High performance conference in

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

    Germany Jackie Chen to give keynote address at ISC High performance conference in Germany - Sandia Energy Energy Search Icon Sandia Home Locations Contact Us Employee Locator Energy & Climate Secure & Sustainable Energy Future Stationary Power Energy Conversion Efficiency Solar Energy Wind Energy Water Power Supercritical CO2 Geothermal Natural Gas Safety, Security & Resilience of the Energy Infrastructure Energy Storage Nuclear Power & Engineering Grid Modernization Battery

  3. 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.

  4. 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.

  5. IXPUG ISC15 Documents

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

    C15-BoF-Preconditioning.pdf | pdf | 1.2 MB Workshop: Language Impact on Vectorization: Vector Programming in CC++ July 16, 2015 | Author(s): Guilherme Amadio | Download File:...

  6. IXPUG ISC15 Documents

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

    Language Impact on Vectorization: Vector Programming in CC++ July 16, 2015 | Author(s): Guilherme Amadio | Download File: Language-Impact-on-Vectorization-Vector-Programming-in-C+...

  7. IXPUG ISC15 Documents

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

    Workshop: Language Impact on Vectorization: Vector Programming in CC++ July 16, 2015 | Author(s): Guilherme Amadio | Download File: Language-Impact-on-Vectorization-Vector-Program...

  8. ISC2005v2.ppt

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

    * In this presentation (ca. 1990) Jack Dongarra lists seven approaches to parallel processing * Note that message passing libraries are a sub-item on 2) Parallel Programming 1994...

  9. ISC15 Workshop for Intel Xeon ...

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

    Intel Xeon Phi TM Processors Guilherme Amadio So Paulo State University (UNESP) Language Impact on Vectorization: Vector Programming in CC++ Vector Programming in CC++ -...

  10. Inhibition of selectin binding

    DOE Patents [OSTI]

    Nagy, Jon O. (Rodeo, CA); Spevak, Wayne R. (Albany, CA); Dasgupta, Falguni (New Delhi, IN); Bertozzi, Caroline (Albany, CA)

    2001-10-09

    This invention provides compositions for inhibiting the binding between two cells, one expressing P- or L-selectin on the surface and the other expressing the corresponding ligand. A covalently crosslinked lipid composition is prepared having saccharides and acidic group on separate lipids. The composition is then interposed between the cells so as to inhibit binding. Inhibition can be achieved at an effective oligosaccharide concentration as low as 10.sup.6 fold below that of the free saccharide. Since selectins are involved in recruiting cells to sites of injury, these composition scan be used to palliate certain inflammatory and immunological conditions.

  11. Inhibition of selectin binding

    DOE Patents [OSTI]

    Nagy, Jon O. (Rodeo, CA); Spevak, Wayne R. (Albany, CA); Dasgupta, Falguni (New Delhi, IN); Bertozzi, Carolyn (Albany, CA)

    1999-10-05

    This invention provides a system for inhibiting the binding between two cells, one expressing P- or L-selectin on the surface and the other expressing the corresponding ligand. A covalently crosslinked lipid composition is prepared having saccharides and acidic group on separate lipids. The composition is then interposed between the cells so as to inhibit binding. Inhibition can be achieved at an effective oligosaccharide concentration as low as 10.sup.6 fold below that of the free saccharide. Since selectins are involved in recruiting cells to sites of injury, this system can be used to palliate certain inflammatory and immunological conditions.

  12. Inhibition of selectin binding

    DOE Patents [OSTI]

    Nagy, Jon O. (Rodeo, CA); Spevak, Wayne R. (Albany, CA); Dasgupta, Falguni (New Delhi, IN); Bertozzi, Caroline (Albany, CA)

    1999-01-01

    This invention provides compositions for inhibiting the binding between two cells, one expressing P- or L-selectin on the surface and the other expressing the corresponding ligand. A covalently crosslinked lipid composition is prepared having saccharides and acidic group on separate lipids. The composition is then interposed between the cells so as to inhibit binding. Inhibition can be achieved at an effective oligosaccharide concentration as low as 10.sup.6 fold below that of the free saccharide. Since selectins are involved in recruiting cells to sites of injury, these composition scan be used to palliate certain inflammatory and immunological conditions.

  13. 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.

  14. 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.

  15. How Dynein Binds to Microtubules

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

    how it binds to microtubules and gives some hints into the fascinating question of how communication passes along the stalk from the MTBD to the rest of the motor. Lucky Break...

  16. How Dynein Binds to Microtubules

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

    How Dynein Binds to Microtubules How Dynein Binds to Microtubules Print Wednesday, 29 April 2009 00:00 Cytoplasmic dynein is a protein complex responsible for the transport of a large variety of cargoes, from specific RNAs and proteins to whole 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 disease-related processes, including the transport of viruses,

  17. 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.

  18. 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.

  19. 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.

  20. ISC-Reducing Congestion through Smart Parking Management | Open...

    Open Energy Info (EERE)

    Sector: Climate, Energy Focus Area: Transportation Resource Type: Case studiesexamples, Lessons learnedbest practices Website: www.iscvt.orgresourcesdocuments...

  1. How Dynein Binds to Microtubules

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

    How Dynein Binds to Microtubules Print Cytoplasmic dynein is a protein complex responsible for the transport of a large variety of cargoes, from specific RNAs and proteins to whole 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 disease-related processes, including the transport of viruses, neurodegeneration, and the mitotic checkpoint malfunctions that lead to

  2. How Dynein Binds to Microtubules

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

    How Dynein Binds to Microtubules Print Cytoplasmic dynein is a protein complex responsible for the transport of a large variety of cargoes, from specific RNAs and proteins to whole 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 disease-related processes, including the transport of viruses, neurodegeneration, and the mitotic checkpoint malfunctions that lead to

  3. How Dynein Binds to Microtubules

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

    How Dynein Binds to Microtubules Print Cytoplasmic dynein is a protein complex responsible for the transport of a large variety of cargoes, from specific RNAs and proteins to whole 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 disease-related processes, including the transport of viruses, neurodegeneration, and the mitotic checkpoint malfunctions that lead to

  4. Erythropoietin binding protein from mammalian serum

    DOE Patents [OSTI]

    Clemons, Gisela K.

    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. Synthetic heparin-binding factor analogs

    DOE Patents [OSTI]

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

    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.

  7. Binding Organic Liquids - Energy Innovation Portal

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

    More Like This Return to Search Binding Organic Liquids Pacific Northwest National Laboratory Contact PNNL About This Technology Technology Marketing Summary Researchers at...

  8. Nicotinamide mononucleotide adenylyltransferase displays alternate binding

    Office of Scientific and Technical Information (OSTI)

    modes for nicotinamide nucleotides (Journal Article) | SciTech Connect Nicotinamide mononucleotide adenylyltransferase displays alternate binding modes for nicotinamide nucleotides Citation Details In-Document Search Title: Nicotinamide mononucleotide adenylyltransferase displays alternate binding modes for nicotinamide nucleotides Authors: Pfoh, Roland ; Pai, Emil F. ; Saridakis, Vivian [1] ; Toronto) [2] + Show Author Affiliations (York) ( Publication Date: 2015-11-23 OSTI Identifier:

  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. 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.

  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. Fragment-Based Exploration of Binding Site Flexibility in Mycobacteriu...

    Office of Scientific and Technical Information (OSTI)

    Fragment-Based Exploration of Binding Site Flexibility in Mycobacterium tuberculosis BioA Citation Details In-Document Search Title: Fragment-Based Exploration of Binding Site ...

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

    DOE Patents [OSTI]

    Mayfield, Stephen

    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.

  14. 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.

  15. Exciton binding energy in semiconductor quantum dots

    SciTech Connect (OSTI)

    Pokutnii, S. I.

    2010-04-15

    In the adiabatic approximation in the context of the modified effective mass approach, in which the reduced exciton effective mass {mu} = {mu}(a) is a function of the radius a of the semiconductor quantum dot, an expression for the exciton binding energy E{sub ex}(a) in the quantum dot is derived. It is found that, in the CdSe and CdS quantum dots with the radii a comparable to the Bohr exciton radii a{sub ex}, the exciton binding energy E{sub ex}(a) is substantially (respectively, 7.4 and 4.5 times) higher than the exciton binding energy in the CdSe and CdS single crystals.

  16. Stabilized sulfur binding using activated fillers

    DOE Patents [OSTI]

    Kalb, Paul D.; Vagin, Vyacheslav P.; Vagin, Sergey P.

    2015-07-21

    A method of making a stable, sulfur binding composite comprising impregnating a solid aggregate with an organic modifier comprising unsaturated hydrocarbons with at least one double or triple covalent bond between adjacent carbon atoms to create a modifier-impregnated aggregate; heating and drying the modifier-impregnated aggregate to activate the surface of the modifier-impregnated aggregate for reaction with sulfur.

  17. 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.

  18. 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.

  19. X-ray crystallographic analysis of adipocyte fatty acid binding...

    Office of Scientific and Technical Information (OSTI)

    binding protein (aP2) modified with 4-hydroxy-2-nonenal Citation Details In-Document Search Title: X-ray crystallographic analysis of adipocyte fatty acid binding protein (aP2) ...

  20. Multidomain Carbohydrate-binding Proteins Involved in Bacteroides...

    Office of Scientific and Technical Information (OSTI)

    Title: Multidomain Carbohydrate-binding Proteins Involved in Bacteroides thetaiotaomicron Starch Metabolism Authors: Cameron, Elizabeth A. ; Maynard, Mallory A. ; Smith, ...

  1. Dual chain synthetic heparin-binding growth factor analogs

    DOE Patents [OSTI]

    Zamora, Paul O.; Pena, Louis A.; Lin, Xinhua

    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.

  2. Dual chain synthetic heparin-binding growth factor analogs

    DOE Patents [OSTI]

    Zamora, Paul O.; Pena, Louis A.; Lin, Xinhua

    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.

  3. Gene encoding herbicide safener binding protein

    DOE Patents [OSTI]

    Walton, Jonathan D.; Scott-Craig, John S.

    1999-01-01

    The cDNA encoding safener binding protein (SafBP), also referred to as SBP1, is set forth in FIG. 5 and SEQ ID No. 1. The deduced amino acid sequence is provided in FIG. 5 and SEQ ID No. 2. Methods of making and using SBP1 and SafBP to alter a plant's sensitivity to certain herbicides or a plant's responsiveness to certain safeners are also provided, as well as expression vectors, transgenic plants or other organisms transfected with said vectors and seeds from said plants.

  4. 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.

  5. Method and apparatus for detecting chemical binding

    DOE Patents [OSTI]

    Warner, Benjamin P.; Havrilla, George J.; Miller, Thomasin C.; Wells, Cyndi A.

    2007-07-10

    The method for screening binding between a target binder and potential pharmaceutical chemicals involves sending a solution (preferably an aqueous solution) of the target binder through a conduit to a size exclusion filter, the target binder being too large to pass through the size exclusion filter, and then sending a solution of one or more potential pharmaceutical chemicals (preferably an aqueous solution) through the same conduit to the size exclusion filter after target binder has collected on the filter. The potential pharmaceutical chemicals are small enough to pass through the filter. Afterwards, x-rays are sent from an x-ray source to the size exclusion filter, and if the potential pharmaceutical chemicals form a complex with the target binder, the complex produces an x-ray fluorescence signal having an intensity that indicates that a complex has formed.

  6. Method And Apparatus For Detecting Chemical Binding

    DOE Patents [OSTI]

    Warner, Benjamin P.; Havrilla, George J.; Miller, Thomasin C.; Wells, Cyndi A.

    2005-02-22

    The method for screening binding between a target binder and potential pharmaceutical chemicals involves sending a solution (preferably an aqueous solution) of the target binder through a conduit to a size exclusion filter, the target binder being too large to pass through the size exclusion filter, and then sending a solution of one or more potential pharmaceutical chemicals (preferably an aqueous solution) through the same conduit to the size exclusion filter after target binder has collected on the filter. The potential pharmaceutical chemicals are small enough to pass through the filter. Afterwards, x-rays are sent from an x-ray source to the size exclusion filter, and if the potential pharmaceutical chemicals form a complex with the target binder, the complex produces an x-ray fluorescence signal having an intensity that indicates that a complex has formed.

  7. 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.

  8. Hardware device to physical structure binding and authentication

    DOE Patents [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.

  9. The Effects of Somatic Hypermutation on Neutralization and Binding...

    Office of Scientific and Technical Information (OSTI)

    Hypermutation on Neutralization and Binding in the PGT121 Family of Broadly Neutralizing HIV Antibodies Citation Details In-Document Search Title: The Effects of Somatic...

  10. Developing Adnectins That Target SRC Co-Activator Binding to...

    Office of Scientific and Technical Information (OSTI)

    Developing Adnectins That Target SRC Co-Activator Binding to PXR: A Structural Approach toward Understanding Promiscuity of PXR Citation Details In-Document Search Title: ...

  11. Structural and functional analysis of FIP2 binding to theendosome...

    Office of Scientific and Technical Information (OSTI)

    Journal Article: Structural and functional analysis of FIP2 binding to the endosome-localised Rab25 GTPase Citation Details In-Document Search Title: Structural and functional ...

  12. Multidomain Carbohydrate-binding Proteins Involved in Bacteroides

    Office of Scientific and Technical Information (OSTI)

    thetaiotaomicron Starch Metabolism (Journal Article) | SciTech Connect Multidomain Carbohydrate-binding Proteins Involved in Bacteroides thetaiotaomicron Starch Metabolism Citation Details In-Document Search Title: Multidomain Carbohydrate-binding Proteins Involved in Bacteroides thetaiotaomicron Starch Metabolism Authors: Cameron, Elizabeth A. ; Maynard, Mallory A. ; Smith, Christopher J. ; Smith, Thomas J. ; Koropatkin, Nicole M. ; Martens, Eric C. [1] ; Danforth) [2] + Show Author

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

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

    The Road to Application Performance on Intel Xeon Phi July 16, 2015 SIMD: CilkPlus and OpenMP Kent Milfeld, Georg Zitzlsberger, Michael Klemm, Carlos Rosales 1 SIMD 2 Single Instruction Multiple Data (SIMD) Data Registers Intel Cilk Plus SIMD Directive Declaration Examples OpenMP SIMD Directive Declaration SIMD loop SIMD CilkPlus OpenMP SIMD mapping Alignment & Elemental Functions Alignment Beyond Present Directives SIMD 3 Single Instruction Multiple Data (SIMD) Data Registers Playground

  14. ISC Conventional Reading Rooms | U.S. DOE Office of Science ...

    Office of Science (SC) Website

    Integrated Support Center Roxanne Purucker U.S. Department of Energy 9800 S. Cass Avenue ... at 865-574-3521, toll free at 800-382-6938, option 6; or via e-mail at DOEIC@oro.doe.gov. ...

  15. 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.

  16. 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:...

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

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

    Complexes with Glutarimidedioxime Sequestering Uranium from Seawater: Binding Strength and Modes of Uranyl Complexes with Glutarimidedioxime Sequestering Uranium from Seawater: Binding Strength and Modes of Uranyl Complexes with Glutarimidedioxime Print Sunday, 14 October 2012 00:00 The ocean is an important source of uranium if it can be extracted economically. Extraction of uranium from seawater is very challenging, not only because it is in an extremely low concentration, but also because

  18. Briefly Bound to Activate: Transient Binding of a Second Catalytic

    Office of Scientific and Technical Information (OSTI)

    Magnesium Activates the Structure and Dynamics of CDK2 Kinase for Catalysis (Journal Article) | SciTech Connect SciTech Connect Search Results Journal Article: Briefly Bound to Activate: Transient Binding of a Second Catalytic Magnesium Activates the Structure and Dynamics of CDK2 Kinase for Catalysis Citation Details In-Document Search Title: Briefly Bound to Activate: Transient Binding of a Second Catalytic Magnesium Activates the Structure and Dynamics of CDK2 Kinase for Catalysis We have

  19. Fragment-Based Exploration of Binding Site Flexibility in Mycobacterium

    Office of Scientific and Technical Information (OSTI)

    tuberculosis BioA (Journal Article) | SciTech Connect Fragment-Based Exploration of Binding Site Flexibility in Mycobacterium tuberculosis BioA Citation Details In-Document Search Title: Fragment-Based Exploration of Binding Site Flexibility in Mycobacterium tuberculosis BioA Authors: Dai, Ran ; Geders, Todd W. ; Liu, Feng ; Park, Sae Woong ; Schnappinger, Dirk ; Aldrich, Courtney C. ; Finzel, Barry C. [1] ; Weill-Med) [2] + Show Author Affiliations (UMM) ( Publication Date: 2015-09-29 OSTI

  20. DNA-Binding Mechanism in Prokaryotic Partition Complex Formation

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

    DNA-Binding Mechanism in Prokaryotic Partition Complex Formation DNA-Binding Mechanism in Prokaryotic Partition Complex Formation Print Wednesday, 29 March 2006 00:00 The faithful inheritance of genetic information, essential for all organisms, requires accurate movement and positioning of replicated DNA to daughter cells during cell division. In cells without distinct nuclei (prokaryotes), this process, called partition or segregation, is mediated by par systems. The prototype system of

  1. Characterization of Selective Binding of Alkali Cations with Carboxylate

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

    Characterization of Selective Binding of Alkali Cations with Carboxylate Characterization of Selective Binding of Alkali Cations with Carboxylate Print Wednesday, 24 September 2008 00:00 During its lifetime, a cell spends a considerable fraction of its energy pumping sodium and calcium out and potassium in. This balancing process is similar to that found in the coils of the DNA double helix, where specific ions nestle and help stabilize this macromolecule. These are only two examples of

  2. Binding Behavior of Dopamine Transporter Key to Understanding Chemical

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

    Reactions in the Brain Binding Behavior of Dopamine Transporter Key to Understanding Chemical Reactions in the Brain Binding Behavior of Dopamine Transporter Key to Understanding Chemical Reactions in the Brain Print Wednesday, 09 December 2015 00:00 Most people have heard of adrenaline, the chemical that causes the "fight or flight" reaction in humans. Most people have also heard of the chemical substances cocaine and methamphetamine, which also elicit a particular (perhaps

  3. Computational Biology: A Recipe for Ligand-Binding Proteins

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

    Computational Biology: A Recipe for Ligand-Binding Proteins Authors: Ghirlanda, G. Title: Computational Biology: A Recipe for Ligand-Binding Proteins Source: Nature Year: 2013 Volume: 501 Pages: 177-178 ABSTRACT: Cellular cross-talk, enzymatic catalysis and regulation of gene expression all depend on molecular recognition. A method that allows the design of proteins with desired recognition sites could thus be revolutionary Date of online publication: Thu, 2013-09-12 Link online:

  4. Structural and functional analysis of FIP2 binding to the

    Office of Scientific and Technical Information (OSTI)

    endosome-localised Rab25 GTPase (Journal Article) | SciTech Connect Journal Article: Structural and functional analysis of FIP2 binding to the endosome-localised Rab25 GTPase Citation Details In-Document Search Title: Structural and functional analysis of FIP2 binding to the endosome-localised Rab25 GTPase Authors: Lall, Patrick ; Horgan, Conor P. ; Oda, Shunichiro ; Franklin, Edward ; Sultana, Azmiri ; Hanscom, Sara R. ; McCaffrey, Mary W. ; Khan, Amir R. [1] ; Cork) [2] + Show Author

  5. Structural basis for biomolecular recognition in overlapping binding sites

    Office of Scientific and Technical Information (OSTI)

    in a diiron enzyme system (Journal Article) | SciTech Connect Structural basis for biomolecular recognition in overlapping binding sites in a diiron enzyme system Citation Details In-Document Search Title: Structural basis for biomolecular recognition in overlapping binding sites in a diiron enzyme system Authors: Acheson, Justin F. ; Bailey, Lucas J. ; Elsen, Nathaniel L. ; Fox, Brian G. [1] + Show Author Affiliations UW Publication Date: 2016-01-22 OSTI Identifier: 1229904 Resource Type:

  6. 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 themore » hexameric 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

  7. Structure and Ca[superscript 2+]-Binding Properties of the Tandem...

    Office of Scientific and Technical Information (OSTI)

    and Casuperscript 2+-Binding Properties of the Tandem Csubscript 2 Domains of E-Syt2 Citation Details In-Document Search Title: Structure and Casuperscript 2+-Binding ...

  8. Molecular dynamics investigation of the substrate binding mechanism in carboxylesterase

    SciTech Connect (OSTI)

    Chen, Qi; Luan, Zheng-Jiao; Cheng, Xiaolin; Xu, Jian-he

    2015-01-01

    A recombinant carboxylesterase, cloned from Pseudomonas putida and designated as rPPE, is capable of catalyzing the bioresolution of racemic 2-acetoxy-2-(2 -chlorophenyl)acetate (rac-AcO-CPA) with excellent (S)-enantioselectivity. Semi-rational design of the enzyme showed that the W187H variant could increase the activity by ~100-fold compared to the wild type (WT) enzyme. In this study, we performed all-atom molecular dynamics (MD) simulations of both apo-rPPE and rPPE in complex with (S)-AcO-CPA to gain insights into the origin of the increased catalysis in the W187H mutant. Our results show differential binding of (S)-AcO-CPA in the WT and W187H enzymes, especially the interactions of the substrate with the two active site residues Ser159 and His286. The replacement of Trp187 by His leads to considerable structural rearrangement in the active site of W187H. Unlike in the WT rPPE, the cap domain in the W187 mutant shows an open conformation in the simulations of both apo and substrate-bound enzymes. This open conformation exposes the catalytic triad to the solvent through a water accessible channel, which may facilitate the entry of the substrate and/or the exit of the product. Binding free energy calculations confirmed that the substrate binds more strongly in W187H than in WT. Based on these computational results, we further predicted that the mutations W187Y and D287G might also be able to increase the substrate binding, thus improve the enzyme s catalytic efficiency. Experimental binding and kinetic assays on W187Y and D287G show improved catalytic efficiency over WT, but not W187H. Contrary to our prediction, W187Y shows slightly decreased substrate binding coupled with a 100 fold increase in turn-over rate, while in D287G the substrate binding is 8 times stronger but with a slightly reduced turn-over rate. Our work provides important molecular-level insights into the binding of the (S)-AcO-CPA substrate to carboxylesterase rPPEs, which will help guide future development of more efficient rPPE variants.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. Binding Behavior of Dopamine Transporter Key to Understanding Chemical

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

    Reactions in the Brain Binding Behavior of Dopamine Transporter Key to Understanding Chemical Reactions in the Brain Print Most people have heard of adrenaline, the chemical that causes the "fight or flight" reaction in humans. Most people have also heard of the chemical substances cocaine and methamphetamine, which also elicit a particular (perhaps desired) human response. What most people do not know is that the same receptors in the human brain recognize the natural, or

  19. Binding Behavior of Dopamine Transporter Key to Understanding Chemical

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

    Reactions in the Brain Binding Behavior of Dopamine Transporter Key to Understanding Chemical Reactions in the Brain Print Most people have heard of adrenaline, the chemical that causes the "fight or flight" reaction in humans. Most people have also heard of the chemical substances cocaine and methamphetamine, which also elicit a particular (perhaps desired) human response. What most people do not know is that the same receptors in the human brain recognize the natural, or

  20. Binding Behavior of Dopamine Transporter Key to Understanding Chemical

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

    Reactions in the Brain Binding Behavior of Dopamine Transporter Key to Understanding Chemical Reactions in the Brain Print Most people have heard of adrenaline, the chemical that causes the "fight or flight" reaction in humans. Most people have also heard of the chemical substances cocaine and methamphetamine, which also elicit a particular (perhaps desired) human response. What most people do not know is that the same receptors in the human brain recognize the natural, or

  1. 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.

  2. DNA-Binding Mechanism in Prokaryotic Partition Complex Formation

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

    DNA-Binding Mechanism in Prokaryotic Partition Complex Formation Print The faithful inheritance of genetic information, essential for all organisms, requires accurate movement and positioning of replicated DNA to daughter cells during cell division. In cells without distinct nuclei (prokaryotes), this process, called partition or segregation, is mediated by par systems. The prototype system of prokaryotic partition is the Escherichia coli P1 plasmid par system, which consists of a centromere

  3. Characterization of Selective Binding of Alkali Cations with Carboxylate

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

    Characterization of Selective Binding of Alkali Cations with Carboxylate Print During its lifetime, a cell spends a considerable fraction of its energy pumping sodium and calcium out and potassium in. This balancing process is similar to that found in the coils of the DNA double helix, where specific ions nestle and help stabilize this macromolecule. These are only two examples of selective ion interactions in biology; there are many others also vital to life. The existence of these interactions

  4. Characterization of Selective Binding of Alkali Cations with Carboxylate

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

    Characterization of Selective Binding of Alkali Cations with Carboxylate Print During its lifetime, a cell spends a considerable fraction of its energy pumping sodium and calcium out and potassium in. This balancing process is similar to that found in the coils of the DNA double helix, where specific ions nestle and help stabilize this macromolecule. These are only two examples of selective ion interactions in biology; there are many others also vital to life. The existence of these interactions

  5. Characterization of Selective Binding of Alkali Cations with Carboxylate

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

    Characterization of Selective Binding of Alkali Cations with Carboxylate Print During its lifetime, a cell spends a considerable fraction of its energy pumping sodium and calcium out and potassium in. This balancing process is similar to that found in the coils of the DNA double helix, where specific ions nestle and help stabilize this macromolecule. These are only two examples of selective ion interactions in biology; there are many others also vital to life. The existence of these interactions

  6. Binding Behavior of Dopamine Transporter Key to Understanding Chemical

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

    Reactions in the Brain Binding Behavior of Dopamine Transporter Key to Understanding Chemical Reactions in the Brain Print Most people have heard of adrenaline, the chemical that causes the "fight or flight" reaction in humans. Most people have also heard of the chemical substances cocaine and methamphetamine, which also elicit a particular (perhaps desired) human response. What most people do not know is that the same receptors in the human brain recognize the natural, or

  7. DNA-Binding Mechanism in Prokaryotic Partition Complex Formation

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

    DNA-Binding Mechanism in Prokaryotic Partition Complex Formation Print The faithful inheritance of genetic information, essential for all organisms, requires accurate movement and positioning of replicated DNA to daughter cells during cell division. In cells without distinct nuclei (prokaryotes), this process, called partition or segregation, is mediated by par systems. The prototype system of prokaryotic partition is the Escherichia coli P1 plasmid par system, which consists of a centromere

  8. Characterization of Selective Binding of Alkali Cations with Carboxylate

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

    Characterization of Selective Binding of Alkali Cations with Carboxylate Print During its lifetime, a cell spends a considerable fraction of its energy pumping sodium and calcium out and potassium in. This balancing process is similar to that found in the coils of the DNA double helix, where specific ions nestle and help stabilize this macromolecule. These are only two examples of selective ion interactions in biology; there are many others also vital to life. The existence of these interactions

  9. Characterization of Selective Binding of Alkali Cations with Carboxylate

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

    Characterization of Selective Binding of Alkali Cations with Carboxylate Print During its lifetime, a cell spends a considerable fraction of its energy pumping sodium and calcium out and potassium in. This balancing process is similar to that found in the coils of the DNA double helix, where specific ions nestle and help stabilize this macromolecule. These are only two examples of selective ion interactions in biology; there are many others also vital to life. The existence of these interactions

  10. Protein Immobilization in Metal-Organic Frameworks by Covalent Binding |

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

    Center for Gas SeparationsRelevant to Clean Energy Technologies | Blandine Jerome Protein Immobilization in Metal-Organic Frameworks by Covalent Binding Previous Next List Xuan Wang, Trevor A. Makal and Hong-Cai Zhou, Aust. J. Chem. 67, 1629-1631 (2014) DOI: 10.1071/CH14104 CH14104_TOC Abstract: Metal-organic frameworks (MOFs), possessing a well defined system of pores, demonstrate extensive potential serving as a platform in biological catalysis. Successful immobilization of enzymes in a

  11. 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.

  12. Gold Binding by Native and Chemically Modified Hops Biomasses

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

    López, M. Laura; Gardea-Torresdey, J. L.; Peralta-Videa, J. R.; de la Rosa, G.; Armendáriz, 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 bindingmore » at 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

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

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

    8: Microsoft Internet Explorer CDwnBindInfo Object Reuse Flaw Lets Remote Users Execute Arbitrary Code V-058: Microsoft Internet Explorer CDwnBindInfo Object Reuse Flaw Lets Remote...

  14. New Insights into the RNA-Binding and E3 Ubiquitin Ligase Activities...

    Office of Scientific and Technical Information (OSTI)

    New Insights into the RNA-Binding and E3 Ubiquitin Ligase Activities of Roquins Citation Details In-Document Search Title: New Insights into the RNA-Binding and E3 Ubiquitin Ligase...

  15. Plasticity of the Quinone-binding Site of the Complex II Homolog...

    Office of Scientific and Technical Information (OSTI)

    Plasticity of the Quinone-binding Site of the Complex II Homolog Quinol:Fumarate Reductase Citation Details In-Document Search Title: Plasticity of the Quinone-binding Site of the...

  16. Discovery of a new ATP-binding motif involved in peptidic azoline...

    Office of Scientific and Technical Information (OSTI)

    Discovery of a new ATP-binding motif involved in peptidic azoline biosynthesis Citation Details In-Document Search Title: Discovery of a new ATP-binding motif involved in peptidic ...

  17. 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.

  18. Reversible CO Binding in Metal-Organic Frameworks | Center for Gas

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

    SeparationsRelevant to Clean Energy Technologies | Blandine Jerome Reversible CO Binding in Metal-Organic Frameworks

  19. Analytical models of calcium binding in a calcium channel

    SciTech Connect (OSTI)

    Liu, Jinn-Liang; Eisenberg, Bob

    2014-08-21

    The anomalous mole fraction effect of L-type calcium channels is analyzed using a Fermi like distribution with the experimental data of Almers and McCleskey [J. Physiol. 353, 585 (1984)] and the atomic resolution model of Lipkind and Fozzard [Biochemistry 40, 6786 (2001)] of the selectivity filter of the channel. Much of the analysis is algebraic, independent of differential equations. The Fermi distribution is derived from the configuration entropy of ions and water molecules with different sizes, different valences, and interstitial voids between particles. It allows us to calculate potentials and distances (between the binding ion and the oxygen ions of the glutamate side chains) directly from the experimental data using algebraic formulas. The spatial resolution of these results is comparable with those of molecular models, but of course the accuracy is no better than that implied by the experimental data. The glutamate side chains in our model are flexible enough to accommodate different types of binding ions in different bath conditions. The binding curves of Na{sup +} and Ca{sup 2+} for [CaCl{sub 2}] ranging from 10{sup −8} to 10{sup −2} M with a fixed 32 mM background [NaCl] are shown to agree with published Monte Carlo simulations. The Poisson-Fermi differential equation—that includes both steric and correlation effects—is then used to obtain the spatial profiles of energy, concentration, and dielectric coefficient from the solvent region to the filter. The energy profiles of ions are shown to depend sensitively on the steric energy that is not taken into account in the classical rate theory. We improve the rate theory by introducing a steric energy that lumps the effects of excluded volumes of all ions and water molecules and empty spaces between particles created by Lennard-Jones type and electrostatic forces. We show that the energy landscape varies significantly with bath concentrations. The energy landscape is not constant.

  20. 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.

  1. 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

  2. Breaking the ties that bind: New hope for biomass fuels

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

    New hope for biomass fuels Breaking the ties that bind: New hope for biomass fuels Researchers have discovered a potential chink in the armor of fibers that make the cell walls of certain inedible plant materials so tough. April 22, 2009 Los Alamos National Laboratory sits on top of a once-remote mesa in northern New Mexico with the Jemez mountains as a backdrop to research and innovation covering multi-disciplines from bioscience, sustainable energy sources, to plasma physics and new materials.

  3. 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.

  4. Highly-Selective and Reversible O2 Binding in

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

    Cr3(1,3,5-benzenetricarboxylate)2 | Center for Gas SeparationsRelevant to Clean Energy Technologies | Blandine Jerome Highly-Selective and Reversible O2 Binding in Cr3(1,3,5-benzenetricarboxylate)2 Previous Next List Leslie J. Murray, Mircea Dinca, Junko Yano, Sachin Chavan, Silvia Bordiga, Craig M. Brown and Jeffrey R. Long, J. Am. Chem. Soc., 2010, 132 (23), pp 7856-7857 DOI: 10.1021/ja1027925 Abstract Image Abstract: Reaction of Cr(CO)6 with trimesic acid in DMF affords the metal-organic

  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. New perspective on glycoside hydrolase binding to lignin from pretreated corn stover

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

    Yarbrough, John M.; Mittal, Ashutosh; Mansfield, Elisabeth; Taylor, II, Larry E.; Hobdey, Sarah E.; Sammond, Deanne W.; Bomble, Yannick J.; Crowley, Michael F.; Decker, Stephen R.; Himmel, Michael E.; et al

    2015-12-18

    In this study, non-specific binding of cellulases to lignin has been implicated as a major factor in the loss of cellulase activity during biomass conversion to sugars. It is believed that this binding may strongly impact process economics through loss of enzyme activities during hydrolysis and enzyme recycling scenarios. The current model suggests glycoside hydrolase activities are lost though non-specific/non-productive binding of carbohydrate-binding domains to lignin, limiting catalytic site access to the carbohydrate components of the cell wall.

  7. U-227: bind-dyndb-ldap DN Escaping Flaw Lets Remote Users Deny Service

    Broader source: Energy.gov [DOE]

    A vulnerability has been reported in bind-dyndb-ldap, which can be exploited by malicious people to cause a DoS (Denial of Service).

  8. 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.

  9. 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.

  10. 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.

  11. 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.

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

    SciTech Connect (OSTI)

    Fagan, P A

    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.

  13. 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.

  14. 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.

  15. X-ray crystallographic analysis of adipocyte fatty acid binding protein

    Office of Scientific and Technical Information (OSTI)

    (aP2) modified with 4-hydroxy-2-nonenal (Journal Article) | SciTech Connect X-ray crystallographic analysis of adipocyte fatty acid binding protein (aP2) modified with 4-hydroxy-2-nonenal Citation Details In-Document Search Title: X-ray crystallographic analysis of adipocyte fatty acid binding protein (aP2) modified with 4-hydroxy-2-nonenal Fatty acid binding proteins (FABP) have been characterized as facilitating the intracellular solubilization and transport of long-chain fatty acyl

  16. Investigation of the mode of binding of a novel series ofN-benzyl...

    Office of Scientific and Technical Information (OSTI)

    of the hepatitis C viral polymerase are described herein. These compounds bind to the hepatitis C virus non-structural protein 5B (NS5B), and co-crystal structures of select...

  17. Capture and release of acid-gasses with acid-gas binding organic compounds

    DOE Patents [OSTI]

    Heldebrant, David J; Yonker, Clement R; Koech, Phillip K

    2015-03-17

    A system and method for acid-gas capture wherein organic acid-gas capture materials form hetero-atom analogs of alkyl-carbonate when contacted with an acid gas. These organic-acid gas capture materials include combinations of a weak acid and a base, or zwitterionic liquids. This invention allows for reversible acid-gas binding to these organic binding materials thus allowing for the capture and release of one or more acid gases. These acid-gas binding organic compounds can be regenerated to release the captured acid gasses and enable these organic acid-gas binding materials to be reused. This enables transport of the liquid capture compounds and the release of the acid gases from the organic liquid with significant energy savings compared to current aqueous systems.

  18. Structure of Human Toll-like Receptor 3 (TLR3) Ligand-binding...

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

    Human Toll-like Receptor 3 (TLR3) Ligand-binding Domain Jungwoo Choe1, Matthew S. Kelker1, and Ian A. Wilson1 1Department of Molecular Biology and The Skaggs Institute for Chemical...

  19. Novel CO2 Binding Mechanism Determined via in-situ Absorption Spectroscopy

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

    & Theory | Center for Gas SeparationsRelevant to Clean Energy Technologies | Blandine Jerome Novel CO2 Binding Mechanism Determined via in-situ Absorption Spectroscopy & Theory

  20. Metal binding in an aluminum based metal-organic framework for carbon

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

    dioxide capture | Center for Gas SeparationsRelevant to Clean Energy Technologies | Blandine Jerome Metal binding in an aluminum based metal-organic framework for carbon dioxide capture

  1. Developing Adnectins That Target SRC Co-Activator Binding to PXR: A

    Office of Scientific and Technical Information (OSTI)

    Structural Approach toward Understanding Promiscuity of PXR (Journal Article) | SciTech Connect Developing Adnectins That Target SRC Co-Activator Binding to PXR: A Structural Approach toward Understanding Promiscuity of PXR Citation Details In-Document Search Title: Developing Adnectins That Target SRC Co-Activator Binding to PXR: A Structural Approach toward Understanding Promiscuity of PXR Authors: Khan, Javed A. ; Camac, Daniel M. ; Low, Simon ; Tebben, Andrew J. ; Wensel, David L. ;

  2. Discovery of a new ATP-binding motif involved in peptidic azoline

    Office of Scientific and Technical Information (OSTI)

    biosynthesis (Journal Article) | SciTech Connect Discovery of a new ATP-binding motif involved in peptidic azoline biosynthesis Citation Details In-Document Search Title: Discovery of a new ATP-binding motif involved in peptidic azoline biosynthesis Authors: Dunbar, Kyle L. ; Chekan, Jonathan R. ; Cox, Courtney L. ; Burkhart, Brandon J. ; Nair, Satish K. ; Mitchell , Douglas A. [1] + Show Author Affiliations (UIUC) Publication Date: 2014-11-20 OSTI Identifier: 1163365 Resource Type: Journal

  3. Memo Is Homologous to Nonheme Iron Dioxygenases and Binds an ErbB2-derived

    Office of Scientific and Technical Information (OSTI)

    Phosphopeptide in Its Vestigial Active Site (Journal Article) | SciTech Connect SciTech Connect Search Results Journal Article: Memo Is Homologous to Nonheme Iron Dioxygenases and Binds an ErbB2-derived Phosphopeptide in Its Vestigial Active Site Citation Details In-Document Search Title: Memo Is Homologous to Nonheme Iron Dioxygenases and Binds an ErbB2-derived Phosphopeptide in Its Vestigial Active Site Authors: Qiu, Chen ; Lienhard, Susanne ; Hynes, Nancy E. ; Badache, Ali ; Leahy, Daniel

  4. The same pocket in menin binds both MLL and JUND but has opposite effects

    Office of Scientific and Technical Information (OSTI)

    on transcription (Journal Article) | SciTech Connect SciTech Connect Search Results Journal Article: The same pocket in menin binds both MLL and JUND but has opposite effects on transcription Citation Details In-Document Search Title: The same pocket in menin binds both MLL and JUND but has opposite effects on transcription Menin is a tumour suppressor protein whose loss or inactivation causes multiple endocrine neoplasia 1 (MEN1), a hereditary autosomal dominant tumour syndrome that is

  5. A Novel Mechanism for Binding of Galactose-terminated Glycans by the C-type

    Office of Scientific and Technical Information (OSTI)

    Carbohydrate Recognition Domain in Blood Dendritic Cell Antigen 2 (Journal Article) | SciTech Connect A Novel Mechanism for Binding of Galactose-terminated Glycans by the C-type Carbohydrate Recognition Domain in Blood Dendritic Cell Antigen 2 Citation Details In-Document Search Title: A Novel Mechanism for Binding of Galactose-terminated Glycans by the C-type Carbohydrate Recognition Domain in Blood Dendritic Cell Antigen 2 Authors: Jégouzo, Sabine A.F. ; Feinberg, Hadar ; Dungarwalla,

  6. Designing artificial metal binding peptides | Center for Bio-Inspired Solar

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

    Fuel Production artificial metal binding peptides 24 Oct 2012 Dong Wang is a graduate student in the Department of Chemistry and Biochemistry at Arizona State University. He is working in the lab of Professor James Allen, who is leading the Subtask 2 of the Bisfuel Center (Water oxidation catalysts). Dong's research project is focused on design and characterization of artificial peptides capable of binding divalent metals with the aim to construct an efficient water oxidation catalyst that

  7. Oligomycin frames a common drug-binding site in the ATP synthase

    SciTech Connect (OSTI)

    Symersky, Jindrich; Osowski, Daniel; Walters, D. Eric; Mueller, David M.

    2015-12-01

    We report the high-resolution (1.9 {angstrom}) crystal structure of oligomycin bound to the subunit c10 ring of the yeast mitochondrial ATP synthase. Oligomycin binds to the surface of the c10 ring making contact with two neighboring molecules at a position that explains the inhibitory effect on ATP synthesis. The carboxyl side chain of Glu59, which is essential for proton translocation, forms an H-bond with oligomycin via a bridging water molecule but is otherwise shielded from the aqueous environment. The remaining contacts between oligomycin and subunit c are primarily hydrophobic. The amino acid residues that form the oligomycin-binding site are 100% conserved between human and yeast but are widely different from those in bacterial homologs, thus explaining the differential sensitivity to oligomycin. Prior genetics studies suggest that the oligomycin-binding site overlaps with the binding site of other antibiotics, including those effective against Mycobacterium tuberculosis, and thereby frames a common 'drug-binding site.' We anticipate that this drug-binding site will serve as an effective target for new antibiotics developed by rational design.

  8. 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.

  9. 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.

  10. 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 alsomore » represents 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

  11. Modulation of FadR Binding Capacity for Acyl-CoA Fatty Acids Through Structure-Guided Mutagenesis

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

    Bacik, John-Paul; Yeager, Chris M.; Twary, Scott N.; Martí-Arbona, Ricardo

    2015-09-18

    FadR is a versatile global regulator in Escherichia coli that controls fatty acid metabolism and thereby modulates the ability of this bacterium to grow using fatty acids or acetate as the sole carbon source. FadR regulates fatty acid metabolism in response to intra-cellular concentrations of acyl-CoA lipids. The ability of FadR to bind acyl-CoA fatty acids is hence of significant interest for the engineering of biosynthetic pathways for the production of lipid-based biofuels and commodity chemicals. Based on the available crystal structure of E. coli bound to myristoyl- CoA, we predicted amino acid positions within the effector binding pocket thatmore » would alter the ability of FadR to bind acyl-CoA fatty acids without affecting DNA binding. We utilized fluorescence polarization to characterize the in-vitro binding properties of wild type and mutant FadR. We found that a Leu102Ala mutant enhanced binding of the effector, likely by increasing the size of the binding pocket for the acyl moiety of the molecule. Conversely, the elimination of the guanidine side chain (Arg213Ala and Arg213Met mutants) of the CoA moiety binding site severely diminished the ability of FadR to bind the acyl-CoA effector. These results demonstrate the ability to fine tune FadR binding capacity. The validation of an efficient method to fully characterize all the binding events involved in the specific activity (effector and DNA operator binding) of FadR has allowed us to increase our understanding of the role of specific amino acids in the binding and recognition of acyl-CoA fatty acids and will greatly facilitate efforts aimed at engineering tunable FadR regulators for synthetic biology.« less

  12. 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.

  13. Nucleotide-binding flexibility in ultrahigh-resolution structures of the SRP GTPase Ffh

    SciTech Connect (OSTI)

    Ramirez, Ursula D.; Focia, Pamela J.; Freymann, Douglas M.

    2008-10-01

    Crystal structures of the Ffh NG GTPase domain at < 1.24 resolution reveal multiple overlapping nucleotide binding modes. Two structures of the nucleotide-bound NG domain of Ffh, the GTPase subunit of the bacterial signal recognition particle (SRP), have been determined at ultrahigh resolution in similar crystal forms. One is GDP-bound and one is GMPPCP-bound. The asymmetric unit of each structure contains two protein monomers, each of which exhibits differences in nucleotide-binding conformation and occupancy. The GDP-bound Ffh NG exhibits two binding conformations in one monomer but not the other and the GMPPCP-bound protein exhibits full occupancy of the nucleotide in one monomer but only partial occupancy in the other. Thus, under the same solution conditions, each crystal reveals multiple binding states that suggest that even when nucleotide is bound its position in the Ffh NG active site is dynamic. Some differences in the positioning of the bound nucleotide may arise from differences in the crystal-packing environment and specific factors that have been identified include the relative positions of the N and G domains, small conformational changes in the P-loop, the positions of waters buried within the active site and shifts in the closing loop that packs against the guanine base. However, loose binding may have biological significance in promoting facile nucleotide exchange and providing a mechanism for priming the SRP GTPase prior to its activation in its complex with the SRP receptor.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. De novo Design of an Artificial bis-[4Fe4S] Binding Protein

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

    De novo Design of an Artificial bis-[4Fe4S] Binding Protein Authors: Roy, A,, Sarrou, I., Vaughn, M.D., Astashkin, A.V., and Ghirlanda, G. Title: De novo Design of an Artificial bis-[4Fe4S] Binding Protein Source: Biochemistry Year: 2013 Volume: 52 Pages: 7586-7594 ABSTRACT: In nature, protein subunits containing multiple iron-sulfur clusters often mediate the delivery of reducing equivalents from metabolic pathways to the active site of redox proteins. The de novo design of redox active

  3. Structural Basis of Wnt Signaling Inhibition by Dickkopf Binding to LRP5/6

    Office of Scientific and Technical Information (OSTI)

    (Journal Article) | SciTech Connect Basis of Wnt Signaling Inhibition by Dickkopf Binding to LRP5/6 Citation Details In-Document Search Title: Structural Basis of Wnt Signaling Inhibition by Dickkopf Binding to LRP5/6 Authors: Ahn, Victoria E. ; Chu, Matthew Ling-Hon ; Choi, Hee-Jung ; Tran, Denise ; Abo, Arie ; Weis, William I. Publication Date: 2011-11-01 OSTI Identifier: 1198118 Type: Published Article Journal Name: Developmental Cell Additional Journal Information: Journal Volume: 21;

  4. Structural Studies of Wnts and Identification of an LRP6 Binding Site

    Office of Scientific and Technical Information (OSTI)

    (Journal Article) | SciTech Connect Structural Studies of Wnts and Identification of an LRP6 Binding Site Citation Details In-Document Search Title: Structural Studies of Wnts and Identification of an LRP6 Binding Site Authors: Chu, Matthew Ling-Hon ; Ahn, Victoria E. ; Choi, Hee-Jung ; Daniels, Danette L. ; Nusse, Roel ; Weis, William I. ; , Publication Date: 2014-05-13 OSTI Identifier: 1131442 Report Number(s): SLAC-REPRINT-2014-111 DOE Contract Number: AC02-76SF00515 Resource Type:

  5. Structure and Ca[superscript 2+]-Binding Properties of the Tandem

    Office of Scientific and Technical Information (OSTI)

    C[subscript 2] Domains of E-Syt2 (Journal Article) | SciTech Connect and Ca[superscript 2+]-Binding Properties of the Tandem C[subscript 2] Domains of E-Syt2 Citation Details In-Document Search Title: Structure and Ca[superscript 2+]-Binding Properties of the Tandem C[subscript 2] Domains of E-Syt2 Authors: Xu, Junjie ; Bacaj, Taulant ; Zhou, Amy ; Tomchick, Diana R. ; Südhof, Thomas C. ; Rizo, Josep [1] ; UTSMC) [2] + Show Author Affiliations (Stanford-MED) ( Publication Date: 2014-12-23

  6. Syntaxin 1a Variants Lacking an N-peptide or Bearing the LE Mutation Bind

    Office of Scientific and Technical Information (OSTI)

    to Munc18a in a Closed Conformation (Journal Article) | SciTech Connect Syntaxin 1a Variants Lacking an N-peptide or Bearing the LE Mutation Bind to Munc18a in a Closed Conformation Citation Details In-Document Search Title: Syntaxin 1a Variants Lacking an N-peptide or Bearing the LE Mutation Bind to Munc18a in a Closed Conformation Authors: Colbert, Karen N. ; Hattendorf, Douglas A. ; Weiss, Thomas M. ; Burkhardt, Pawel ; Fasshauer, Dirk ; Weis, William I. Publication Date: 2014-05-13 OSTI

  7. 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.

  8. 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.

  9. 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.

  10. Nucleotide-binding flexibility in ultrahigh-resolution structures of the SRP GTPase Ffh

    SciTech Connect (OSTI)

    Ramirez, U.D.; Focia, P.J.; Freymann, D.M.

    2008-10-24

    Two structures of the nucleotide-bound NG domain of Ffh, the GTPase subunit of the bacterial signal recognition particle (SRP), have been determined at ultrahigh resolution in similar crystal forms. One is GDP-bound and one is GMPPCP-bound. The asymmetric unit of each structure contains two protein monomers, each of which exhibits differences in nucleotide-binding conformation and occupancy. The GDP-bound Ffh NG exhibits two binding conformations in one monomer but not the other and the GMPPCP-bound protein exhibits full occupancy of the nucleotide in one monomer but only partial occupancy in the other. Thus, under the same solution conditions, each crystal reveals multiple binding states that suggest that even when nucleotide is bound its position in the Ffh NG active site is dynamic. Some differences in the positioning of the bound nucleotide may arise from differences in the crystal-packing environment and specific factors that have been identified include the relative positions of the N and G domains, small conformational changes in the P-loop, the positions of waters buried within the active site and shifts in the closing loop that packs against the guanine base. However, 'loose' binding may have biological significance in promoting facile nucleotide exchange and providing a mechanism for priming the SRP GTPase prior to its activation in its complex with the SRP receptor.

  11. NRC staff review of licensee responses to pressure-locking and thermal-binding issue

    SciTech Connect (OSTI)

    Rathbun, H.J.

    1996-12-01

    Commercial nuclear power plant operating experience has indicated that pressure locking and thermal binding represent potential common mode failure mechanisms that can cause safety-related power-operated gate valves to fail in the closed position, thus rendering redundant safety-related systems incapable of performing their safety functions. In Generic Letter (GL) 95-07, {open_quotes}Pressure Locking and Thermal Binding of Safety-Related Power-Operated Gate Valves,{close_quotes} the U.S. Nuclear Regulatory Commission (NRC) staff requested that nuclear power plant licensees take certain actions to ensure that valves susceptible to pressure locking or thermal binding are capable of performing their safety functions within the current licensing bases of the facility. The NRC staff has received summary information from licensees in response to GL 95-07 describing actions they have taken to prevent the occurrence of pressure locking and thermal binding. The NRC staff has developed a systematic process to help ensure uniform and consistent review of licensee submittals in response to GL 95-07.

  12. 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.

  13. 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.

  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. V-008: Debian Security Advisory | Department of Energy

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

    08: Debian Security Advisory V-008: Debian Security Advisory October 23, 2012 - 6:00am Addthis PROBLEM: Debian Security Advisory PLATFORM: Debian GNU/Linux 6.0 ABSTRACT: Debian update for bind9 REFERENCE LINKS: Debian Security Advisory DSA-2560-1 Debian bugtracking system: Bug 690118 ISC Reference Number: AA-00801 Secunia Advisory SA51054 CVE-2012-5166 IMPACT ASSESSMENT: Medium DISCUSSION: was discovered that BIND, a DNS server, hangs while constructing the additional section of a DNS reply,

  16. Identification of the heparin binding site on adeno-associated virus serotype 3B (AAV-3B)

    SciTech Connect (OSTI)

    Lerch, Thomas F.; Chapman, Michael S.

    2012-02-05

    Adeno-associated virus is a promising vector for gene therapy. In the current study, the binding site on AAV serotype 3B for the heparan sulfate proteoglycan (HSPG) receptor has been characterized. X-ray diffraction identified a disaccharide binding site at the most positively charged region on the virus surface. The contributions of basic amino acids at this and other sites were characterized using site-directed mutagenesis. Both heparin and cell binding are correlated to positive charge at the disaccharide binding site, and transduction is significantly decreased in AAV-3B vectors mutated at this site to reduce heparin binding. While the receptor attachment sites of AAV-3B and AAV-2 are both in the general vicinity of the viral spikes, the exact amino acids that participate in electrostatic interactions are distinct. Diversity in the mechanisms of cell attachment by AAV serotypes will be an important consideration for the rational design of improved gene therapy vectors.

  17. Identification of the heparin binding site on adeno-associated virus serotype 3B (AAV-3B)

    SciTech Connect (OSTI)

    Lerch, Thomas F.; Chapman, Michael S.

    2012-05-24

    Adeno-associated virus is a promising vector for gene therapy. In the current study, the binding site on AAV serotype 3B for the heparan sulfate proteoglycan (HSPG) receptor has been characterized. X-ray diffraction identified a disaccharide binding site at the most positively charged region on the virus surface. The contributions of basic amino acids at this and other sites were characterized using site-directed mutagenesis. Both heparin and cell binding are correlated to positive charge at the disaccharide binding site, and transduction is significantly decreased in AAV-3B vectors mutated at this site to reduce heparin binding. While the receptor attachment sites of AAV-3B and AAV-2 are both in the general vicinity of the viral spikes, the exact amino acids that participate in electrostatic interactions are distinct. Diversity in the mechanisms of cell attachment by AAV serotypes will be an important consideration for the rational design of improved gene therapy vectors.

  18. 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.

  19. 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.

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

    SciTech Connect (OSTI)

    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 sequence determinants 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.

  1. 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 sequencemore » determinants 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

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

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

    Aradi, Bálint; 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 Born–Oppenheimer 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 materialsmore » science, chemistry, and biology.« less

  3. Quenching methods for background reduction in luminescence-based probe-target binding assays

    DOE Patents [OSTI]

    Cai, Hong (Los Alamos, NM); Goodwin, Peter M (Los Alamos, NM); Keller, Richard A. (Los Alamos, NM); Nolan, Rhiannon L. (Santa Fe, NM)

    2007-04-10

    Background luminescence is reduced from a solution containing unbound luminescent probes, each having a first molecule that attaches to a target molecule and having an attached luminescent moiety, and luminescent probe/target adducts. Quenching capture reagent molecules are formed that are capable of forming an adduct with the unbound luminescent probes and having an attached quencher material effective to quench luminescence of the luminescent moiety. The quencher material of the capture reagent molecules is added to a solution of the luminescent probe/target adducts and binds in a proximity to the luminescent moiety of the unbound luminescent probes to quench luminescence from the luminescent moiety when the luminescent moiety is exposed to exciting illumination. The quencher capture reagent does not bind to probe molecules that are bound to target molecules and the probe/target adduct emission is not quenched.

  4. 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 hydrophobicmore » environment, 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

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

    SciTech Connect (OSTI)

    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 materials science, chemistry, and biology.

  6. 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).

  7. Ritonavir binds to and downregulates estrogen receptors: Molecular mechanism of promoting early atherosclerosis

    SciTech Connect (OSTI)

    Xiang, Jin; Wang, Ying; Su, Ke; Liu, Min; Hu, Peng-Chao; Ma, Tian; Li, Jia-Xi; Wei, Lei; Zheng, Zhongliang; Yang, Fang

    2014-10-01

    Estrogenic actions are closely related to cardiovascular disease. Ritonavir (RTV), a human immunodeficiency virus (HIV) protease inhibitor, induces atherosclerosis in an estrogen-related manner. However, how RTV induce pathological phenotypes through estrogen pathway remains unclear. In this study, we found that RTV increases thickness of coronary artery walls of Sprague Dawley rats and plasma free fatty acids (FFA) levels. In addition, RTV could induce foam cell formation, downregulate both estrogen receptor ? (ER?) and ER? expression, upregulate G protein-coupled estrogen receptor (GPER) expression, and all of them could be partially blocked by 17?-estradiol (E2), suggesting RTV acts as an antagonist for E2. Computational modeling shows a similar interaction with ER? between RTV and 2-aryl indoles, which are highly subtype-selective ligands for ER?. We also found that RTV directly bound to ER? and selectively inhibited the nuclear localization of ER?, and residue Leu536 in the hydrophobic core of ligand binding domain (LBD) was essential for the interaction with RTV. In addition, RTV did not change the secondary structure of ER?-LBD like E2, which explained how ER? lost the capacity of nuclear translocation under the treatment of RTV. All of the evidences suggest that ritonavir acts as an antagonist for 17?-estradiol in regulating ? subtype estrogen receptor function and early events of atherosclerosis. - Graphical abstract: RTV directly binds to ER? and Leu536 in the hydrophobic core of ligand binding domain is essential for the interaction. - Highlights: RTV increases the thickness of rat coronary artery wall and foam cell formation. RTV downregulates the expression of ER? and ER?. RTV inhibits ER? promoter activity. RTV directly binds to ER? and the key amino acid is Leu536. RTV inhibits the nuclear translocation of ER? and GPER.

  8. Reversible CO-binding to the Active Site of Nitrogenase | Stanford

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

    Synchrotron Radiation Lightsource Reversible CO-binding to the Active Site of Nitrogenase Tuesday, March 31, 2015 All living organisms depend on the availability of nitrogen for incorporation into the basic biological building blocks such as amino acids and DNA. Globally the largest reservoir for nitrogen is the atmosphere, with an N2 content of roughly 78%. However, as a highly unreactive gas, most organisms are unable to directly utilize dinitrogen due to the severe energy barrier required

  9. Model for Eukaryotic Tail-anchored Protein Binding Based on the Structure

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

    of Get3 Model for Eukaryotic Tail-anchored Protein Binding Based on the Structure of Get3 Targeting of newly synthesized membrane proteins to the endoplasmic reticulum (ER) is an important cellular process. Most membrane proteins are recognized and targeted co-translationally by the signal recognition particle (SRP). A number of membrane proteins (eg. SNAREs, apoptosis factors, and protein translocation components) are 'tail-anchored' by a single carboxy-terminal transmembrane domain. Due to

  10. 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 withmore » different 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

  11. 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 thatmore » 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.« less

  12. 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.

  13. 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 ionsmore » that 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

  14. 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.

  15. 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.

  16. 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.

  17. Kinetic and Crystallgraphic Studies of a Redesigned Manganese-Binding Site in Cytochrome c Peroxidase

    SciTech Connect (OSTI)

    Pfister,T.; Mirarefi, A.; Gengenbach, A.; Zhao, X.; Danstrom , C.; Conatser, N.; Gao, Y.; Robinson, H.; Zukoski, C.; et al.

    2007-01-01

    Manganese peroxidase (MnP) from the white rot fungus Phanerochaete chrysosporium contains a manganese-binding site that plays a critical role in its function. Previously, a Mn{sup II}-binding site was designed into cytochrome c peroxidase (CcP) based on sequence homology (Yeung et al. in Chem. Biol. 4:215-222, 1997; Gengenbach et al. in Biochemistry 38:11425-11432, 1999). Here, we report a redesign of this site based on X-ray structural comparison of MnP and CcP. The variant, CcP(D37E, V45E, H181E), displays 2.5-fold higher catalytic efficiency (k{sub cat}/k{sub M}) than the variant in the original design, mostly due to a stronger k{sub M} of 1.9 mM (vs. 4.1 mM). High-resolution X-ray crystal structures of a metal-free form and a form with Co{sup II} at the designed Mn{sup II} site were also obtained. The metal ion in the engineered metal-binding site overlays well with Mn{sup II} bound in MnP, suggesting that this variant is the closest structural model of the Mn{sup II}-binding site in MnP for which a crystal structure exists. A major difference arises in the distances of the ligands to the metal; the metal-ligand interactions in the CcP variant are much weaker than the corresponding interactions in MnP, probably owing to partial occupancy of metal ion at the designed site, difference in the identity of metal ions (Co{sup II} rather than Mn{sup II}) and other interactions in the second coordination sphere. These results indicate that the metal ion, the ligands, and the environment around the metal-binding site play important roles in tuning the structure and function of metalloenzymes.

  18. 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.

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

    SciTech Connect (OSTI)

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

    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 with different 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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

  4. Binding Energies and Melting Temperatures of Heavy Hadrons in Quark-Gluon Plasma

    SciTech Connect (OSTI)

    Narodetskii, I. M.; Simonov, Yu. A.; Veselov, A. I.

    2011-05-23

    We discuss the consequences of the suggestion that the non-perturbative quark-antiquark potential at T{>=}T{sub c}, where T{sub c} is a temperature of a deconfinement phase transition in QCD can be studied through the modification of the correlation functions, which define the quadratic field correlators of the nonperturbative vaccuum fields. We use the non-perturbative quark-antiquark potential derived within the Field Correlator Method and the screened Coulomb potential with T-dependent Debye mass to calculate J/{psi}, {Upsilon} and {Omega}{sub bbb} binding energies and melting temperatures in the deconfined phase of QCD.

  5. Reversible CO Binding Enables Tunable CO/H2 and CO/N2 Separations in

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

    Metal-Organic Frameworks with Exposed Divalent Metal Cations | Center for Gas SeparationsRelevant to Clean Energy Technologies | Blandine Jerome Reversible CO Binding Enables Tunable CO/H2 and CO/N2 Separations in Metal-Organic Frameworks with Exposed Divalent Metal Cations Previous Next List Eric D. Bloch, Matthew R. Hudson, Jarad A. Mason, Sachin Chavan, Valentina Crocellà, Joshua D. Howe, Kyuho Lee, Allison L. Dzubak, Wendy L. Queen, Joseph M. Zadrozny, Stephen J. Geier, Li-Chiang Lin,

  6. Strong and Reversible Binding of Carbon Dioxide in a Green Metal-Organic

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

    Framework | Center for Gas SeparationsRelevant to Clean Energy Technologies | Blandine Jerome Strong and Reversible Binding of Carbon Dioxide in a Green Metal-Organic Framework Previous Next List Jeremiah J. Gassensmith, Hiroyasu Furukawa, Ronald A. Smaldone, Ross S. Forgan, Youssry Y. Botros, Omar M. Yaghi, and J. Fraser Stoddart, J. Am. Chem. Soc., 2011, 133 (39), pp 15312-15315 DOI: 10.1021/ja206525x Abstract Image Abstract: The efficient capture and storage of gaseous CO2 is a pressing

  7. Nuclear binding energy and symmetry energy of nuclear matter with modern nucleon-nucleon potentials

    SciTech Connect (OSTI)

    Hassaneen, Kh.S.A.; Abo-Elsebaa, H.M.; Sultan, E.A.; Mansour, H.M.M.

    2011-03-15

    Research Highlights: > The nuclear matter is studied within the Brueckner-Hartree-Fock (BHF) approach employing the most recent accurate nucleon-nucleon potentials. > The results come out by approximating the single particle self-consistent potential with a parabolic form. > We discuss the current status of the Coester line, i.e., density and energy of the various saturation points being strongly linearly correlated. > The nuclear symmetry energy is calculated as the difference between the binding energy of pure neutron matter and that of symmetric nuclear matter. - Abstract: The binding energy of nuclear matter at zero temperature in the Brueckner-Hartree-Fock approximation with modern nucleon-nucleon potentials is studied. Both the standard and continuous choices of single particle energies are used. These modern nucleon-nucleon potentials fit the deuteron properties and are phase shifts equivalent. Comparison with other calculations is made. In addition we present results for the symmetry energy obtained with different potentials, which is of great importance in astrophysical calculation.

  8. 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.

  9. 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 β-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, themore » 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.« less

  10. 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.

  11. 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.

  12. 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.

  13. Correlating hydrogen oxidation and evolution activity on platinum at different pH with measured hydrogen binding energy

    SciTech Connect (OSTI)

    Sheng, WC; Zhuang, ZB; Gao, MR; Zheng, J; Chen, JGG; Yan, YS

    2015-01-08

    The hydrogen oxidation/evolution reactions are two of the most fundamental reactions in distributed renewable electrochemical energy conversion and storage systems. The identification of the reaction descriptor is therefore of critical importance for the rational catalyst design and development. Here we report the correlation between hydrogen oxidation/evolution activity and experimentally measured hydrogen binding energy for polycrystalline platinum examined in several buffer solutions in a wide range of electrolyte pH from 0 to 13. The hydrogen oxidation/evolution activity obtained using the rotating disk electrode method is found to decrease with the pH, while the hydrogen binding energy, obtained from cyclic voltammograms, linearly increases with the pH. Correlating the hydrogen oxidation/evolution activity to the hydrogen binding energy renders a monotonic decreasing hydrogen oxidation/evolution activity with the hydrogen binding energy, strongly supporting the hypothesis that hydrogen binding energy is the sole reaction descriptor for the hydrogen oxidation/evolution activity on monometallic platinum.

  14. Operating experience feedback report -- Pressure locking and thermal binding of gate valves. Commercial power reactors: Volume 9

    SciTech Connect (OSTI)

    Hsu, C.

    1993-03-01

    The potential for valve inoperability caused by pressure locking and thermal binding has been known for many years in the nuclear industry. Pressure locking or thermal binding is a common-mode failure mechanism that can prevent a gate valve from opening, and could render redundant trains of safety systems or multiple safety systems inoperable. In spite of numerous generic communications issued in the past by the Nuclear Regulatory Commission (NRC) and industry, pressure locking and thermal binding continues to occur to gate valves installed in safety-related systems of both boding water reactors (BWRs) and pressurized water reactors (PWRs). The generic communications to date have not led to effective industry action to fully identify, evaluate, and correct the problem. This report provides a review of operating events involving these failure mechanisms. As a result of this review this report: (1) identifies conditions when the failure mechanisms have occurred, (2) identifies the spectrum of safety systems that have been subjected to the failure mechanisms, and (3) identifies conditions that may introduce the failure mechanisms under both normal and accident conditions. On the basis of the evaluation of the operating events, the Office for Analysis and Evaluation of Operational Data (AEOD) of the NRC concludes that the binding problems with gate valves are an important safety issue that needs priority NRC and industry attention. This report also provides AEOD`s recommendation for actions to effectively prevent the occurrence of valve binding failures.

  15. Transcription Factors Bind Thousands of Active and InactiveRegions in the Drosophila Blastoderm

    SciTech Connect (OSTI)

    Li, Xiao-Yong; MacArthur, Stewart; Bourgon, Richard; Nix, David; Pollard, Daniel A.; Iyer, Venky N.; Hechmer, Aaron; Simirenko, Lisa; Stapleton, Mark; Luengo Hendriks, Cris L.; Chu, Hou Cheng; Ogawa, Nobuo; Inwood, William; Sementchenko, Victor; Beaton, Amy; Weiszmann, Richard; Celniker, Susan E.; Knowles, David W.; Gingeras, Tom; Speed, Terence P.; Eisen, Michael B.; Biggin, Mark D.

    2008-01-10

    Identifying the genomic regions bound by sequence-specific regulatory factors is central both to deciphering the complex DNA cis-regulatory code that controls transcription in metazoans and to determining the range of genes that shape animal morphogenesis. Here, we use whole-genome tiling arrays to map sequences bound in Drosophila melanogaster embryos by the six maternal and gap transcription factors that initiate anterior-posterior patterning. We find that these sequence-specific DNA binding proteins bind with quantitatively different specificities to highly overlapping sets of several thousand genomic regions in blastoderm embryos. Specific high- and moderate-affinity in vitro recognition sequences for each factor are enriched in bound regions. This enrichment, however, is not sufficient to explain the pattern of binding in vivo and varies in a context-dependent manner, demonstrating that higher-order rules must govern targeting of transcription factors. The more highly bound regions include all of the over forty well-characterized enhancers known to respond to these factors as well as several hundred putative new cis-regulatory modules clustered near developmental regulators and other genes with patterned expression at this stage of embryogenesis. The new targets include most of the microRNAs (miRNAs) transcribed in the blastoderm, as well as all major zygotically transcribed dorsal-ventral patterning genes, whose expression we show to be quantitatively modulated by anterior-posterior factors. In addition to these highly bound regions, there are several thousand regions that are reproducibly bound at lower levels. However, these poorly bound regions are, collectively, far more distant from genes transcribed in the blastoderm than highly bound regions; are preferentially found in protein-coding sequences; and are less conserved than highly bound regions. Together these observations suggest that many of these poorly-bound regions are not involved in early-embryonic transcriptional regulation, and a significant proportion may be nonfunctional. Surprisingly, for five of the six factors, their recognition sites are not unambiguously more constrained evolutionarily than the immediate flanking DNA, even in more highly bound and presumably functional regions, indicating that comparative DNA sequence analysis is limited in its ability to identify functional transcription factor targets.

  16. 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

  17. Selectivity in ligand binding to uranyl compounds: A synthetic, structural, thermodynamic and computational study

    SciTech Connect (OSTI)

    Arnold, John

    2015-01-21

    The uranyl cation (UO??) is the most abundant form of uranium on the planet. It is estimated that 4.5 billion tons of uranium in this form exist in sea water. The ability to bind and extract the uranyl cation from aqueous solution while separating it from other elements would provide a limitless source of nuclear fuel. A large body of research concerns the selective recognition and extraction of uranyl. A stable molecule, the cation has a linear O=U=O geometry. The short U-O bonds (1.78 ) arise from the combination of uranium 5f/6d and oxygen 2p orbitals. Due to the oxygen moieties being multiply bonded, these sites were not thought to be basic enough for Lewis acidic coordination to be a viable approach to sequestration.

  18. 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.

  19. 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).

  20. Method for nucleic acid hybridization using single-stranded DNA binding protein

    DOE Patents [OSTI]

    Tabor, Stanley; Richardson, Charles C.

    1996-01-01

    Method of nucleic acid hybridization for detecting the presence of a specific nucleic acid sequence in a population of different nucleic acid sequences using a nucleic acid probe. The nucleic acid probe hybridizes with the specific nucleic acid sequence but not with other nucleic acid sequences in the population. The method includes contacting a sample (potentially including the nucleic acid sequence) with the nucleic acid probe under hybridizing conditions in the presence of a single-stranded DNA binding protein provided in an amount which stimulates renaturation of a dilute solution (i.e., one in which the t.sub.1/2 of renaturation is longer than 3 weeks) of single-stranded DNA greater than 500 fold (i.e., to a t.sub.1/2 less than 60 min, preferably less than 5 min, and most preferably about 1 min.) in the absence of nucleotide triphosphates.

  1. High throughput screening of ligand binding to macromolecules using high resolution powder diffraction

    DOE Patents [OSTI]

    Von Dreele, Robert B.; D'Amico, Kevin

    2006-10-31

    A process is provided for the high throughput screening of binding of ligands to macromolecules using high resolution powder diffraction data including producing a first sample slurry of a selected polycrystalline macromolecule material and a solvent, producing a second sample slurry of a selected polycrystalline macromolecule material, one or more ligands and the solvent, obtaining a high resolution powder diffraction pattern on each of said first sample slurry and the second sample slurry, and, comparing the high resolution powder diffraction pattern of the first sample slurry and the high resolution powder diffraction pattern of the second sample slurry whereby a difference in the high resolution powder diffraction patterns of the first sample slurry and the second sample slurry provides a positive indication for the formation of a complex between the selected polycrystalline macromolecule material and at least one of the one or more ligands.

  2. 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.

  3. 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.

  4. BuD, a helixloophelix DNA-binding domain for genome modification

    SciTech Connect (OSTI)

    Stella, Stefano; Molina, Rafael; Lpez-Mndez, Blanca; Juillerat, Alexandre; Bertonati, Claudia; Daboussi, Fayza; Campos-Olivas, Ramon; Duchateau, Phillippe; Montoya, Guillermo

    2014-07-01

    Crystal structures of BurrH and the BurrHDNA complex are reported. DNA editing offers new possibilities in synthetic biology and biomedicine for modulation or modification of cellular functions to organisms. However, inaccuracy in this process may lead to genome damage. To address this important problem, a strategy allowing specific gene modification has been achieved through the addition, removal or exchange of DNA sequences using customized proteins and the endogenous DNA-repair machinery. Therefore, the engineering of specific proteinDNA interactions in protein scaffolds is key to providing toolkits for precise genome modification or regulation of gene expression. In a search for putative DNA-binding domains, BurrH, a protein that recognizes a 19 bp DNA target, was identified. Here, its apo and DNA-bound crystal structures are reported, revealing a central region containing 19 repeats of a helixloophelix modular domain (BurrH domain; BuD), which identifies the DNA target by a single residue-to-nucleotide code, thus facilitating its redesign for gene targeting. New DNA-binding specificities have been engineered in this template, showing that BuD-derived nucleases (BuDNs) induce high levels of gene targeting in a locus of the human haemoglobin ? (HBB) gene close to mutations responsible for sickle-cell anaemia. Hence, the unique combination of high efficiency and specificity of the BuD arrays can push forward diverse genome-modification approaches for cell or organism redesign, opening new avenues for gene editing.

  5. 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.

  6. Crystal Structure of an Integron Gene Cassette-Associated Protein from Vibrio cholerae Identifies a Cationic Drug-Binding Module

    SciTech Connect (OSTI)

    Deshpande, Chandrika N.; Harrop, Stephen J.; Boucher, Yan; Hassan, Karl A.; Di Leo, Rosa; Xu, Xiaohui; Cui, Hong; Savchenko, Alexei; Chang, Changsoo; Labbate, Maurizio; Paulsen, Ian T.; Stokes, H.W.; Curmi, Paul M.G.; Mabbutt, Bridget C.

    2012-02-15

    The direct isolation of integron gene cassettes from cultivated and environmental microbial sources allows an assessment of the impact of the integron/gene cassette system on the emergence of new phenotypes, such as drug resistance or virulence. A structural approach is being exploited to investigate the modularity and function of novel integron gene cassettes. We report the 1.8 {angstrom} crystal structure of Cass2, an integron-associated protein derived from an environmental V. cholerae. The structure defines a monomeric beta-barrel protein with a fold related to the effector-binding portion of AraC/XylS transcription activators. The closest homologs of Cass2 are multi-drug binding proteins, such as BmrR. Consistent with this, a binding pocket made up of hydrophobic residues and a single glutamate side chain is evident in Cass2, occupied in the crystal form by polyethylene glycol. Fluorescence assays demonstrate that Cass2 is capable of binding cationic drug compounds with submicromolar affinity. The Cass2 module possesses a protein interaction surface proximal to its drug-binding cavity with features homologous to those seen in multi-domain transcriptional regulators. Genetic analysis identifies Cass2 to be representative of a larger family of independent effector-binding proteins associated with lateral gene transfer within Vibrio and closely-related species. We propose that the Cass2 family not only has capacity to form functional transcription regulator complexes, but represents possible evolutionary precursors to multi-domain regulators associated with cationic drug compounds.

  7. 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.

  8. Structural Basis for a Switch in Receptor Binding Specificity of Two H5N1 Hemagglutinin Mutants

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

    Zhu, Xueyong; Viswanathan, Karthik; Raman, Rahul; Yu, Wenli; Sasisekharan, Ram; Wilson, Ian A.

    2015-11-01

    Avian H5N1 influenza viruses continue to spread in wild birds and domestic poultry with sporadic infection in humans. Receptor binding specificity changes are a prerequisite for H5N1 viruses and other zoonotic viruses to be transmitted among humans. Previous reported hemagglutinin (HA) mutants from ferret-transmissible H5N1 viruses of A/Viet Nam/1203/04 and A/Indonesia/5/05 showed slightly increased, but still very weak, binding to human receptors. From mutagenesis and glycan array studies, we previously identified two H5N1 HA mutants that could more effectively switch receptor specificity to human-like α2-6 linked sialosides with avidity comparable to wild-type H5 HA binding to avian-like α2-3 linked sialosides.more »Here, crystal structures of these two H5 HA mutants free and in complex with human and avian glycan receptor analogues reveal the structural basis for their preferential binding to human receptors. These findings suggest continuous surveillance should be maintained to monitor and assess human-to-human transmission potential of H5N1 viruses.« less

  9. 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.

  10. Minimal Determinants for Binding Activated G alpha from the Structure of a G alpha i1-Peptide Dimer

    SciTech Connect (OSTI)

    Johnston,C.; Lobanova, E.; Shavkunov, A.; Low, J.; Ramer, J.; Blasesius, R.; Fredericks, Z.; willard, F.; Kuhlman, B.; et al.

    2006-01-01

    G-Proteins cycle between an inactive GDP-bound state and an active GTP-bound state, serving as molecular switches that coordinate cellular signaling. We recently used phage display to identify a series of peptides that bind G{alpha}subunits in a nucleotide-dependent manner [Johnston, C. A., Willard, F. S., Jezyk, M. R., Fredericks, Z., Bodor, E. T., Jones, M. B., Blaesius, R., Watts, V. J., Harden, T. K., Sondek, J., Ramer, J. K., and Siderovski, D. P. (2005) Structure 13, 1069-1080]. Here we describe the structural features and functions of KB-1753, a peptide that binds selectively to GDP{center_dot}AlF{sub 4{sup -}}- and GTP{gamma}S-bound states of G{alpha}{sup i} subunits. KB-1753 blocks interaction of G{alpha}{sub transducin} with its effector, cGMP phosphodiesterase, and inhibits transducin-mediated activation of cGMP degradation. Additionally, KB-1753 interferes with RGS protein binding and resultant GAP activity. A fluorescent KB-1753 variant was found to act as a sensor for activated G{alpha} in vitro. The crystal structure of KB-1753 bound to G{alpha}{sub i1}-GDP{center_dot}AlF{sub 4{sup -}} reveals binding to a conserved hydrophobic groove between switch II and 3 helices and, along with supporting biochemical data and previous structural analyses, supports the notion that this is the site of effector interactions for G{alpha}i subunits.

  11. 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.

  12. 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.

  13. 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.

  14. Analysis of hydrogen adsorption and surface binding configuration on tungsten using direct recoil spectrometry

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

    Kolasinski, R. D.; Hammond, K. D.; Whaley, J. A.; Buchenauer, D. A.; Wirth, B. D.

    2014-12-03

    In our work, we apply low energy ion beam analysis to examine directly how the adsorbed hydrogen concentration and binding configuration on W(1 0 0) depend on temperature. We exposed the tungsten surface to fluxes of both atomic and molecular H and D. We then probed the H isotopes adsorbed along different crystal directions using 1–2 keV Ne+ ions. At saturation coverage, H occupies two-fold bridge sites on W(1 0 0) at 25 °C. Moreover, the H coverage dramatically changes the behavior of channeled ions, as does reconstruction of the surface W atoms. For the exposure conditions examined here, wemore » find that surface sites remain populated with H until the surface temperature reaches 200 °C. Then, we observe H rapidly desorbing until only a residual concentration remains at 450 °C. Development of an efficient atomistic model that accurately reproduces the experimental ion energy spectra and azimuthal variation of recoiled H is underway.« less

  15. An Insertion Mutation That Distorts Antibody Binding Site Architecture Enhances Function of a Human Antibody

    SciTech Connect (OSTI)

    Krause, Jens C.; Ekiert, Damian C.; Tumpey, Terrence M.; Smith, Patricia B.; Wilson, Ian A.; Crowe, Jr., James E.

    2011-09-02

    The structural and functional significance of somatic insertions and deletions in antibody chains is unclear. Here, we demonstrate that a naturally occurring three-amino-acid insertion within the influenza virus-specific human monoclonal antibody 2D1 heavy-chain variable region reconfigures the antibody-combining site and contributes to its high potency against the 1918 and 2009 pandemic H1N1 influenza viruses. The insertion arose through a series of events, including a somatic point mutation in a predicted hot-spot motif, introduction of a new hot-spot motif, a molecular duplication due to polymerase slippage, a deletion due to misalignment, and additional somatic point mutations. Atomic resolution structures of the wild-type antibody and a variant in which the insertion was removed revealed that the three-amino-acid insertion near the base of heavy-chain complementarity-determining region (CDR) H2 resulted in a bulge in that loop. This enlarged CDR H2 loop impinges on adjacent regions, causing distortion of the CDR H1 architecture and its displacement away from the antigen-combining site. Removal of the insertion restores the canonical structure of CDR H1 and CDR H2, but binding, neutralization activity, and in vivo activity were reduced markedly because of steric conflict of CDR H1 with the hemagglutinin antigen.

  16. On the Roles of Substrate Binding and Hinge Unfolding in Conformational Changes of Adenylate Kinase

    SciTech Connect (OSTI)

    Brokaw, Jason B.; Chu, Jhih-wei

    2010-11-17

    We characterized the conformational change of adenylate kinase (AK) between open and closed forms by conducting five all-atom molecular-dynamics simulations, each of 100 ns duration. Different initial structures and substrate binding configurations were used to probe the pathways of AK conformational change in explicit solvent, and no bias potential was applied. A complete closed-to-open and a partial open-to-closed transition were observed, demonstrating the direct impact of substrate-mediated interactions on shifting protein conformation. The sampled configurations suggest two possible pathways for connecting the open and closed structures of AK, affirming the prediction made based on available x-ray structures and earlier works of coarse-grained modeling. The trajectories of the all-atom molecular-dynamics simulations revealed the complexity of protein dynamics and the coupling between different domains during conformational change. Calculations of solvent density and density fluctuations surrounding AK did not show prominent variation during the transition between closed and open forms. Finally, we characterized the effects of local unfolding of an important hinge near Pro177 on the closed-to-open transition of AK and identified a novel mechanism by which hinge unfolding modulates protein conformational change. The local unfolding of Pro177 hinge induces alternative tertiary contacts that stabilize the closed structure and prevent the opening transition.

  17. 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.

  18. A Rac1--GDP trimer complex binds zinc with tetrahedral and octahedral coordination, displacing magnesium

    SciTech Connect (OSTI)

    Prehna, G.; Stebbins, C

    2007-01-01

    The Rho family of small GTPases represent well characterized signaling molecules that regulate many cellular functions such as actin cytoskeletal arrangement and the cell cycle by acting as molecular switches. A Rac1-GDP-Zn complex has been crystallized in space group P3221 and its crystal structure has been solved at 1.9 {angstrom} resolution. These trigonal crystals reveal the unexpected ability of Rac1 to coordinate Zn atoms in a tetrahedral fashion by use of its biologically relevant switch I and switch II regions. Upon coordination of zinc, the switch I region is stabilized in the GDP-bound conformation and contributes to a Rac1 trimer in the asymmetric unit. Zinc coordination causes switch II to adopt a novel conformation with a symmetry-related molecule. Additionally, zinc was found to displace magnesium from its octahedral coordination at switch I, although GDP binding remained stable. This structure represents the first reported Rac1-GDP-Zn complex, which further underscores the conformational flexibility and versatility of the small GTPase switch regions.

  19. A Rac1-GDP Trimer Complex Binds Zinc with Tetrahedral and Octahedral Coordination, Displacing Magnesium

    SciTech Connect (OSTI)

    Prehna,G.; Stebbins, E.

    2007-01-01

    The Rho family of small GTPases represent well characterized signaling molecules that regulate many cellular functions such as actin cytoskeletal arrangement and the cell cycle by acting as molecular switches. A Rac1-GDP-Zn complex has been crystallized in space group P3{sub 2}21 and its crystal structure has been solved at 1.9 {angstrom} resolution. These trigonal crystals reveal the unexpected ability of Rac1 to coordinate Zn atoms in a tetrahedral fashion by use of its biologically relevant switch I and switch II regions. Upon coordination of zinc, the switch I region is stabilized in the GDP-bound conformation and contributes to a Rac1 trimer in the asymmetric unit. Zinc coordination causes switch II to adopt a novel conformation with a symmetry-related molecule. Additionally, zinc was found to displace magnesium from its octahedral coordination at switch I, although GDP binding remained stable. This structure represents the first reported Rac1-GDP-Zn complex, which further underscores the conformational flexibility and versatility of the small GTPase switch regions.

  20. 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.

  1. National Environmental Policy Act (NEPA) Documents | U.S. DOE Office of

    Office of Science (SC) Website

    Science (SC) National Environmental Policy Act (NEPA) Documents Integrated Support Center (ISC) ISC Home About Services Freedom of Information Act (FOIA) Privacy Act NEPA Documents ISC-Chicago Office Categorical Exclusion Determinations ISC-Oak Ridge Office Categorical Exclusion Determinations ISC-Chicago Office Environmental Assessments and Environmental Impact Statements ISC-Oak Ridge Office Environmental Assessments and Environmental Impact Statements Contact Information Integrated

  2. 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 Nishina, Hiroshi

    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.

  3. 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.

  4. 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.

  5. 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.

  6. Identical phosphatase mechanisms achieved through distinct modes of binding phosphoprotein substrate

    SciTech Connect (OSTI)

    Pazy, Y.; Motaleb, M.A.; Guarnieri, M.T.; Charon, N.W.; Zhao, R.; Silversmith, R.E.

    2010-04-05

    Two-component signal transduction systems are widespread in prokaryotes and control numerous cellular processes. Extensive investigation of sensor kinase and response regulator proteins from many two-component systems has established conserved sequence, structural, and mechanistic features within each family. In contrast, the phosphatases which catalyze hydrolysis of the response regulator phosphoryl group to terminate signal transduction are poorly understood. Here we present structural and functional characterization of a representative of the CheC/CheX/FliY phosphatase family. The X-ray crystal structure of Borrelia burgdorferi CheX complexed with its CheY3 substrate and the phosphoryl analogue BeF{sub 3}{sup -} reveals a binding orientation between a response regulator and an auxiliary protein different from that shared by every previously characterized example. The surface of CheY3 containing the phosphoryl group interacts directly with a long helix of CheX which bears the conserved (E - X{sub 2} - N) motif. Conserved CheX residues Glu96 and Asn99, separated by a single helical turn, insert into the CheY3 active site. Structural and functional data indicate that CheX Asn99 and CheY3 Thr81 orient a water molecule for hydrolytic attack. The catalytic residues of the CheX-CheY3 complex are virtually superimposable on those of the Escherichia coli CheZ phosphatase complexed with CheY, even though the active site helices of CheX and CheZ are oriented nearly perpendicular to one other. Thus, evolution has found two structural solutions to achieve the same catalytic mechanism through different helical spacing and side chain lengths of the conserved acid/amide residues in CheX and CheZ.

  7. Energy Savings Performance Contracts (ESPCs) | U.S. DOE Office...

    Office of Science (SC) Website

    Energy Savings Performance Contracts (ESPCs) Integrated Support Center (ISC) ISC Home ... Integrated Support Center Roxanne Purucker U.S. Department of Energy 9800 S. Cass Avenue ...

  8. The R6A-1 peptide binds to switch II of G{alpha}{sub i1} but is not a GDP-dissociation inhibitor

    SciTech Connect (OSTI)

    Willard, Francis S. . E-mail: fwillard@med.unc.edu; Siderovski, David P.

    2006-01-27

    Heterotrimeric G-proteins are molecular switches that convert signals from membrane receptors into changes in intracellular physiology. Recently, several peptides that bind heterotrimeric G-protein {alpha} subunits have been isolated including the novel G{alpha}{sub i1} . GDP binding peptides R6A and KB-752. The R6A peptide and its minimized derivative R6A-1 interact with G{alpha}{sub i1} . GDP. Based on spectroscopic analysis of BODIPYFL-GTP{gamma}S binding to G{alpha}{sub i1}, it has been reported that R6A-1 has guanine nucleotide dissociation inhibitor (GDI) activity against G{alpha}{sub i1} [W.W. Ja, R.W. Roberts, Biochemistry 43 (28) (2004) 9265-9275]. Using radioligand binding, we show that R6A-1 is not a GDI for G{alpha}{sub i1} subunits. Furthermore, we demonstrate that R6A-1 reduces the fluorescence quantum yield of the G{alpha}{sub i1}-BODIPYFL-GTP{gamma}S complex, thus explaining the previously reported GDI activity as a fluorescence artifact. We further show that R6A-1 has significant sequence similarity to the guanine nucleotide exchange factor peptide KB-752 that binds to switch II of G{alpha}{sub i1}. We use competitive binding analysis to show that R6A-1 also binds to switch II of G{alpha} subunits.

  9. 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 thenmore » applied 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

  10. 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 ofmore » IgG 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

  11. Numerical calculation of protein-ligand binding rates through solution of the Smoluchowski equation using smoothed particle hydrodynamics

    SciTech Connect (OSTI)

    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 then applied 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.

  12. Electronic Structures, Bonding Configurations, and Band-Gap-Opening Properties of Graphene Binding with Low-Concentration Fluorine

    SciTech Connect (OSTI)

    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 above the 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.

  13. 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.

  14. 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 abovemore » the 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

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. Selective Binding of O2 over N2 in a Redox-Active Metal-Organic Framework

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

    with Open Iron(II) Coordination Sites | Center for Gas SeparationsRelevant to Clean Energy Technologies | Blandine Jerome Selective Binding of O2 over N2 in a Redox-Active Metal-Organic Framework with Open Iron(II) Coordination Sites Previous Next List E. D. Bloch, L. J. Murray, W. L. Queen, S. Chavan, S. N. Maximoff, J. P. Bigi, R. Krishna, V. K. Peterson, F. Grandjean, G. J. Long, B. Smit, S. Bordiga, C. M. Brown, and J. R. Long, J. Am. Chem. Soc. 133 (37), 14814 (2011) DOI:

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. Numerical calculation of protein-ligand binding rates through solution of the Smoluchowski equation using smooth particle hydrodynamics

    SciTech Connect (OSTI)

    Pan, Wenxiao; Daily, Michael D.; Baker, Nathan A.

    2015-12-01

    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. The numerical method is first verified in simple systems and then applied to the calculation of ligand binding to an acetylcholinesterase monomer. Unlike previous studies, a reactive Robin boundary condition (BC), rather than the absolute absorbing (Dirichlet) boundary condition, is considered on the reactive boundaries. This new boundary condition treatment allows for the analysis of enzymes with "imperfect" reaction rates. 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. 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.

  6. 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.

  7. 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.

  8. Molecular-Scale Features that Govern the Effects of O-Glycosylation on a Carbohydrate-Binding Module

    SciTech Connect (OSTI)

    Guan, Xiaoyang; Chaffey, Patrick K.; Zeng, Chen; Greene, Eric R.; Chen, Liqun; Drake, Matthew R.; Chen, Claire; Groobman, Ari; Resch, Michael G.; Himmel, Michael E.; Beckham, Gregg T.; Tan, Zhongping

    2015-09-21

    The protein glycosylation is a ubiquitous post-translational modification in all kingdoms of life. Despite its importance in molecular and cellular biology, the molecular-level ramifications of O-glycosylation on biomolecular structure and function remain elusive. Here, we took a small model glycoprotein and changed the glycan structure and size, amino acid residues near the glycosylation site, and glycosidic linkage while monitoring any corresponding changes to physical stability and cellulose binding affinity. The results of this study reveal the collective importance of all the studied features in controlling the most pronounced effects of O-glycosylation in this system. This study suggests the possibility of designing proteins with multiple improved properties by simultaneously varying the structures of O-glycans and amino acids local to the glycosylation site.

  9. Molecular-Scale Features that Govern the Effects of O-Glycosylation on a Carbohydrate-Binding Module

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

    Guan, Xiaoyang; Chaffey, Patrick K.; Zeng, Chen; Greene, Eric R.; Chen, Liqun; Drake, Matthew R.; Chen, Claire; Groobman, Ari; Resch, Michael G.; Himmel, Michael E.; et al

    2015-09-21

    The protein glycosylation is a ubiquitous post-translational modification in all kingdoms of life. Despite its importance in molecular and cellular biology, the molecular-level ramifications of O-glycosylation on biomolecular structure and function remain elusive. Here, we took a small model glycoprotein and changed the glycan structure and size, amino acid residues near the glycosylation site, and glycosidic linkage while monitoring any corresponding changes to physical stability and cellulose binding affinity. The results of this study reveal the collective importance of all the studied features in controlling the most pronounced effects of O-glycosylation in this system. This study suggests the possibility ofmore » designing proteins with multiple improved properties by simultaneously varying the structures of O-glycans and amino acids local to the glycosylation site.« less

  10. 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.

    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})

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. First-principles investigation on the electronic efficiency and binding energy of the contacts formed by graphene and poly-aromatic hydrocarbon anchoring groups

    SciTech Connect (OSTI)

    Li, Yang; Tu, Xingchen; Wang, Hao; Hou, Shimin; Sanvito, Stefano

    2015-04-28

    The electronic efficiency and binding energy of contacts formed between graphene electrodes and poly-aromatic hydrocarbon (PAH) anchoring groups have been investigated by the non-equilibrium Greens function formalism combined with density functional theory. Our calculations show that PAH molecules always bind in the interior and at the edge of graphene in the AB stacking manner, and that the binding energy increases following the increase of the number of carbon and hydrogen atoms constituting the PAH molecule. When we move to analyzing the electronic transport properties of molecular junctions with a six-carbon alkyne chain as the central molecule, the electronic efficiency of the graphene-PAH contacts is found to depend on the energy gap between the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) of the corresponding PAH anchoring group, rather than its size. To be specific, the smaller is the HOMO-LUMO gap of the PAH anchoring group, the higher is the electronic efficiency of the graphene-PAH contact. Although the HOMO-LUMO gap of a PAH molecule depends on its specific configuration, PAH molecules with similar atomic structures show a decreasing trend for their HOMO-LUMO gap as the number of fused benzene rings increases. Therefore, graphene-conjugated molecule-graphene junctions with high-binding and high-conducting graphene-PAH contacts can be realized by choosing appropriate PAH anchor groups with a large area and a small HOMO-LUMO gap.

  16. 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.

  17. 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.

  18. 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.

  19. Strain-Specific V3 and CD4 Binding Site Autologous HIV-1 Neutralizing Antibodies Select Neutralization-Resistant Viruses

    SciTech Connect (OSTI)

    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; Lloyd, Krissey E.; Hwang, Kwan-Ki; Lu, Xiaozhi; Bonsignori, Mattia; Finzi, Andrs; Vandergrift, Nathan A.; Alam, S. Munir; Ferrari, Guido; Shen, Xiaoying; Tomaras, Georgia D.; Kamanga, Gift; Cohen, Myron S.; Sam, Noel E.; Kapiga, Saidi; Gray, Elin S.; Tumba, Nancy L.; Morris, Lynn; Zolla-Pazner, Susan; Gorny, Miroslaw K.; Mascola, John R.; Hahn, Beatrice H.; Shaw, George M.; Sodroski, Joseph G.; Liao, Hua-Xin; Montefiori, DavidC.; Hraber, PeterT.; Korber, BetteT.; Haynes, BartonF.

    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 tier 2 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.

  20. Free energy of RNA-counterion interactions in a tight-binding model computed by a discrete space mapping

    SciTech Connect (OSTI)

    Henke, Paul S.; Mak, Chi H.

    2014-08-14

    The thermodynamic stability of a folded RNA is intricately tied to the counterions and the free energy of this interaction must be accounted for in any realistic RNA simulations. Extending a tight-binding model published previously, in this paper we investigate the fundamental structure of charges arising from the interaction between small functional RNA molecules and divalent ions such as Mg{sup 2+} that are especially conducive to stabilizing folded conformations. The characteristic nature of these charges is utilized to construct a discretely connected energy landscape that is then traversed via a novel application of a deterministic graph search technique. This search method can be incorporated into larger simulations of small RNA molecules and provides a fast and accurate way to calculate the free energy arising from the interactions between an RNA and divalent counterions. The utility of this algorithm is demonstrated within a fully atomistic Monte Carlo simulation of the P4-P6 domain of the Tetrahymena group I intron, in which it is shown that the counterion-mediated free energy conclusively directs folding into a compact structure.

  1. 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 tiermore » 2 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

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. Binding of flexible and constrained ligands to the Grb2 SH2 domain: structural effects of ligand preorganization

    SciTech Connect (OSTI)

    Clements, John H.; DeLorbe, John E.; Benfield, Aaron P.; Martin, Stephen F.

    2010-10-01

    Structures of the Grb2 SH2 domain complexed with a series of flexible and constrained replacements of the phosphotyrosine residue in tripeptides derived from Ac-pYXN (where X = V, I, E and Q) were compared to determine what, if any, structural differences arise as a result of ligand preorganization. Structures of the Grb2 SH2 domain complexed with a series of pseudopeptides containing flexible (benzyl succinate) and constrained (aryl cyclopropanedicarboxylate) replacements of the phosphotyrosine (pY) residue in tripeptides derived from Ac-pYXN-NH{sub 2} (where X = V, I, E and Q) were elucidated by X-ray crystallography. Complexes of flexible/constrained pairs having the same pY + 1 amino acid were analyzed in order to ascertain what structural differences might be attributed to constraining the phosphotyrosine replacement. In this context, a given structural dissimilarity between complexes was considered to be significant if it was greater than the corresponding difference in complexes coexisting within the same asymmetric unit. The backbone atoms of the domain generally adopt a similar conformation and orientation relative to the ligands in the complexes of each flexible/constrained pair, although there are some significant differences in the relative orientations of several loop regions, most notably in the BC loop that forms part of the binding pocket for the phosphate group in the tyrosine replacements. These variations are greater in the set of complexes of constrained ligands than in the set of complexes of flexible ligands. The constrained ligands make more direct polar contacts to the domain than their flexible counterparts, whereas the more flexible ligand of each pair makes more single-water-mediated contacts to the domain; there was no correlation between the total number of proteinligand contacts and whether the phosphotyrosine replacement of the ligand was preorganized. The observed differences in hydrophobic interactions between the complexes of each flexible/constrained ligand pair were generally similar to those observed upon comparing such contacts in coexisting complexes. The average adjusted B factors of the backbone atoms of the domain and loop regions are significantly greater in the complexes of constrained ligands than in the complexes of the corresponding flexible ligands, suggesting greater thermal motion in the crystalline state in the former complexes. There was no apparent correlation between variations in crystal packing and observed structural differences or similarities in the complexes of flexible and constrained ligands, but the possibility that crystal packing might result in structural variations cannot be rigorously excluded. Overall, it appears that there are more variations in the three-dimensional structure of the protein and the ligand in complexes of the constrained ligands than in those of their more flexible counterparts.

  7. Preferential selection of isomer binding from chiral mixtures: alternate binding modes observed for the E and Z isomers of a series of 5-substituted 2,4-diaminofuro[2,3-d]pyrimidines as ternary complexes with NADPH and human dihydrofolate reductase

    SciTech Connect (OSTI)

    Cody, Vivian; Piraino, Jennifer; Pace, Jim; Li, Wei; Gangjee, Aleem

    2010-12-01

    The structures of six chirally mixed E/Z-isomers of 5-substituted 2,4-diaminofuro[2,3-d]pyrimidines reveals only one isomer is bound in the active site of human DHFR. The configuration of all but one C9-analogue is observed as the E-isomer. The crystal structures of six human dihydrofolate reductase (hDHFR) ternary complexes with NADPH and a series of mixed E/Z isomers of 5-substituted 5-[2-(2-methoxyphenyl)-prop-1-en-1-yl]furo[2,3-d]pyrimidine-2,4-diamines substituted at the C9 position with propyl, isopropyl, cyclopropyl, butyl, isobutyl and sec-butyl (E2E7, Z3) were determined and the results were compared with the resolved E and Z isomers of the C9-methyl parent compound. The configuration of all of the inhibitors, save one, was observed as the E isomer, in which the binding of the furopyrimidine ring is flipped such that the 4-amino group binds in the 4-oxo site of folate. The Z3 isomer of the C9-isopropyl analog has the normal 2,4-diaminopyrimidine ring binding geometry, with the furo oxygen near Glu30 and the 4-amino group interacting near the cofactor nicotinamide ring. Electron-density maps for these structures revealed the binding of only one isomer to hDHFR, despite the fact that chiral mixtures (E:Z ratios of 2:1, 3:1 and 3:2) of the inhibitors were incubated with hDHFR prior to crystallization. Superposition of the hDHFR complexes with E2 and Z3 shows that the 2?-methoxyphenyl ring of E2 is perpendicular to that of Z3. The most potent inhibitor in this series is the isopropyl analog Z3 and the least potent is the isobutyl analog E6, consistent with data that show that the Z isomer makes the most favorable interactions with the active-site residues. The isobutyl moiety of E6 is observed in two orientations and the resultant steric crowding of the E6 analog is consistent with its weaker activity. The alternative binding modes observed for the furopyrimidine ring in these E/Z isomers suggest that new templates can be designed to probe these binding regions of the DHFR active site.

  8. 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.

  9. 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.

    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.

  10. 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 .

  11. Unraveling a Hotspot for TCR Recognition on HLA-A2: Evidence Against the Existence of Peptide-independent TCR Binding Determinants

    SciTech Connect (OSTI)

    Gagnon, Susan J.; Borbulevych, Oleg Y.; Davis-Harrison, Rebecca L.; Baxter, Tiffany K.; Clemens, John R.; Armstrong, Kathryn M.; Turner, Richard V.; Damirjian, Marale; Biddison, William E.; Baker, Brian M.

    2010-07-19

    T cell receptor (TCR) recognition of peptide takes place in the context of the major histocompatibility complex (MHC) molecule, which accounts for approximately two-thirds of the peptide/MHC buried surface. Using the class I MHC HLA-A2 and a large panel of mutants, we have previously shown that surface mutations that disrupt TCR recognition vary with the identity of the peptide. The single exception is Lys66 on the HLA-A2 {alpha}1 helix, which when mutated to alanine disrupts recognition for 93% of over 250 different T cell clones or lines, independent of which peptide is bound. Thus, Lys66 could serve as a peptide-independent TCR binding determinant. Here, we have examined the role of Lys66 in TCR recognition of HLA-A2 in detail. The structure of a peptide/HLA-A2 molecule with the K66A mutation indicates that although the mutation induces no major structural changes, it results in the exposure of a negatively charged glutamate (Glu63) underneath Lys66. Concurrent replacement of Glu63 with glutamine restores TCR binding and function for T cells specific for five different peptides presented by HLA-A2. Thus, the positive charge on Lys66 does not serve to guide all TCRs onto the HLA-A2 molecule in a manner required for productive signaling. Furthermore, electrostatic calculations indicate that Lys66 does not contribute to the stability of two TCR-peptide/HLA-A2 complexes. Our findings are consistent with the notion that each TCR arrives at a unique solution of how to bind a peptide/MHC, most strongly influenced by the chemical and structural features of the bound peptide. This would not rule out an intrinsic affinity of TCRs for MHC molecules achieved through multiple weak interactions, but for HLA-A2 the collective mutational data place limits on the role of any single MHC amino acid side-chain in driving TCR binding in a peptide-independent fashion.

  12. X-ray crystallographic analysis of adipocyte fatty acid binding protein (aP2) modified with 4-hydroxy-2-nonenal

    SciTech Connect (OSTI)

    Hellberg, Kristina; Grimsrud, Paul A.; Kruse, Andrew C.; Banaszak, Leonard J.; Ohlendorf, Douglas H.; Bernlohr, David A.

    2012-07-11

    Fatty acid binding proteins (FABP) have been characterized as facilitating the intracellular solubilization and transport of long-chain fatty acyl carboxylates via noncovalent interactions. More recent work has shown that the adipocyte FABP is also covalently modified in vivo on Cys117 with 4-hydroxy-2-nonenal (4-HNE), a bioactive aldehyde linked to oxidative stress and inflammation. To evaluate 4-HNE binding and modification, the crystal structures of adipocyte FABP covalently and noncovalently bound to 4-HNE have been solved to 1.9 {angstrom} and 2.3 {angstrom} resolution, respectively. While the 4-HNE in the noncovalently modified protein is coordinated similarly to a carboxylate of a fatty acid, the covalent form show a novel coordination through a water molecule at the polar end of the lipid. Other defining features between the two structures with 4-HNE and previously solved structures of the protein include a peptide flip between residues Ala36 and Lys37 and the rotation of the side chain of Phe57 into its closed conformation. Representing the first structure of an endogenous target protein covalently modified by 4-HNE, these results define a new class of in vivo ligands for FABPs and extend their physiological substrates to include bioactive aldehydes.

  13. The nuclear localization of low risk HPV11 E7 protein mediated by its zinc binding domain is independent of nuclear import receptors

    SciTech Connect (OSTI)

    Piccioli, Zachary; McKee, Courtney H.; Leszczynski, Anna; Onder, Zeynep; Hannah, Erin C.; Mamoor, Shahan; Crosby, Lauren; Moroianu, Junona

    2010-11-10

    We investigated the nuclear import of low risk HPV11 E7 protein using 1) transfection assays in HeLa cells with EGFP fusion plasmids containing 11E7 and its domains and 2) nuclear import assays in digitonin-permeabilized HeLa cells with GST fusion proteins containing 11E7 and its domains. The EGFP-11E7 and EGFP-11cE7{sub 39-98} localized mostly to the nucleus. The GST-11E7 and GST-11cE7{sub 39-98} were imported into the nuclei in the presence of either Ran-GDP or RanG19V-GTP mutant and in the absence of nuclear import receptors. This suggests that 11E7 enters the nucleus via a Ran-dependent pathway, independent of nuclear import receptors, mediated by a nuclear localization signal located in its C-terminal domain (cNLS). This cNLS contains the zinc binding domain consisting of two copies of Cys-X-X-Cys motif. Mutagenesis of Cys residues in these motifs changed the localization of the EGFP-11cE7/-11E7 mutants to cytoplasmic, suggesting that the zinc binding domain is essential for nuclear localization of 11E7.

  14. Activated RhoA Binds to the Pleckstrin Homology (PH) Domain of PDZ-RhoGEF, a Potential Site for Autoregulation

    SciTech Connect (OSTI)

    Chen, Zhe; Medina, Frank; Liu, Mu-ya; Thomas, Celestine; Sprang, Stephen R.; Sternweis, Paul C.

    2010-07-19

    Guanine nucleotide exchange factors (GEFs) catalyze exchange of GDP for GTP by stabilizing the nucleotide-free state of the small GTPases through their Dbl homology/pleckstrin homology (DH {center_dot} PH) domains. Unconventionally, PDZ-RhoGEF (PRG), a member of the RGS-RhoGEFs, binds tightly to both nucleotide-free and activated RhoA (RhoA {center_dot} GTP). We have characterized the interaction between PRG and activated RhoA and determined the structure of the PRG-DH {center_dot} PH-RhoA {center_dot} GTP{gamma}S (guanosine 5{prime}-O-[{gamma}-thio]triphosphate) complex. The interface bears striking similarity to a GTPase-effector interface and involves the switch regions in RhoA and a hydrophobic patch in PRG-PH that is conserved among all Lbc RhoGEFs. The two surfaces that bind activated and nucleotide-free RhoA on PRG-DH {center_dot} PH do not overlap, and a ternary complex of PRG-DH {center_dot} PH bound to both forms of RhoA can be isolated by size-exclusion chromatography. This novel interaction between activated RhoA and PH could play a key role in regulation of RhoGEF activity in vivo.

  15. Ion binding compounds, radionuclide complexes, methods of making radionuclide complexes, methods of extracting radionuclides, and methods of delivering radionuclides to target locations

    DOE Patents [OSTI]

    Chen, Xiaoyuan (Syracuse, NY); Wai, Chien M. (Moscow, ID); Fisher, Darrell R. (Richland, WA)

    2000-01-01

    The invention pertains to compounds for binding lanthanide ions and actinide ions. The invention further pertains to compounds for binding radionuclides, and to methods of making radionuclide complexes. Also, the invention pertains to methods of extracting radionuclides. Additionally, the invention pertains to methods of delivering radionuclides to target locations. In one aspect, the invention includes a compound comprising: a) a calix[n]arene group, wherein n is an integer greater than 3, the calix[n]arene group comprising an upper rim and a lower rim; b) at least one ionizable group attached to the lower rim; and c) an ion selected from the group consisting of lanthanide and actinide elements bound to the ionizable group. In another aspect, the invention includes a method of extracting a radionuclide, comprising: a) providing a sample comprising a radionuclide; b) providing a calix[n]arene compound in contact with the sample, wherein n is an integer greater than 3; and c) extracting radionuclide from the sample into the calix[n]arene compound. In yet another aspect, the invention includes a method of delivering a radionuclide to a target location, comprising: a) providing a calix[n]arene compound, wherein n is an integer greater than 3, the calix[n]arene compound comprising at least one ionizable group; b) providing a radionuclide bound to the calix[n]arene compound; and c) providing an antibody attached to the calix[n]arene compound, the antibody being specific for a material found at the target location.

  16. 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.

  17. 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.

  18. 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.

  19. How to Submit a FOIA Request | U.S. DOE Office of Science (SC)

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

    About » Field Offices » ISC Home » Freedom of Information Act (FOIA) » How to Submit a FOIA Request Integrated Support Center (ISC) ISC Home About Services Freedom of Information Act (FOIA) Privacy Act Advisory Exemptions How to Submit a FOIA Request FOIA Request Form Fee Waiver and Reduction Criteria Electronic Reading Room ISC Conventional Reading Rooms Reference Links Privacy Act NEPA Documents Contact Information Integrated Support Center Roxanne Purucker U.S. Department of Energy 9800

  20. Atomistic tight-binding study of electronic structure and interband optical transitions in GaBi{sub x}As{sub 1?x}/GaAs quantum wells

    SciTech Connect (OSTI)

    Usman, Muhammad; O'Reilly, Eoin P.

    2014-02-17

    Large-supercell tight-binding calculations are presented for GaBi{sub x}As{sub 1?x}/GaAs single quantum wells (QWs) with Bi fractions x of 3.125% and 12.5%. Our results highlight significant distortion of the valence band states due to the alloy disorder. A large full-width-half-maximum (FWHM) is estimated in the ground state interband transition energy (?33?meV) at 3.125% Bi, consistent with recent photovoltage measurements for similar Bi compositions. Additionally, the alloy disorder effects are predicted to become more pronounced as the QW width is increased. However, they are less strong at the higher Bi composition (12.5%) required for the design of temperature-stable lasers, with a calculated FWHM of ?23.5?meV at x?=?12.5%.

  1. The Exosporium of B.cereus Contains a Binding Site for gC1qR/p33: Implication in Spore Attachment and/or Entry.

    SciTech Connect (OSTI)

    GHEBREHIWET,B.; TANTRAL, L.; TITMUS, M.A.; PANESSA-WARREN, B.J.; TORTORA, G.T.; WONG, S.S.; WARREN, J.B.

    2008-01-01

    B. cereus, is a member of a genus of aerobic, gram-positive, spore-forming rod-like bacilli, which includes the deadly, B. anthracis. Preliminary experiments have shown that gC1qR binds to B.cereus spores that have been attached to microtiter plates. The present studies were therefore undertaken, to examine if cell surface gC1qR plays a role in B.cereus spore attachment and/or entry. Monolayers of human colon carcinoma (Caco-2) and lung cells were grown to confluency on 6 mm coverslips in shell vials with gentle swirling in a shaker incubator. Then, 2 {micro}l of a suspension of strain SB460 B.cereus spores (3x10{sup 8}/ml, in sterile water), were added and incubated (1-4 h; 36{sup 0} C) in the presence or absence of anti-gC1qR mAb-carbon nanoloops. Examination of these cells by EM revealed that: (1) When B. cereus endospores contacted the apical Caco-2 cell surface, or lung cells, gClqR was simultaneously detectable, indicating upregulation of the molecule. (2) In areas showing spore contact with the cell surface, gClqR expression was often adjacent to the spores in association with microvilli (Caco-2 cells) or cytoskeletal projections (lung cells). (3) Furthermore, the exosporia of the activated and germinating spores were often decorated with mAb-nanoloops. These observations were further corroborated by experiments in which B.cereus spores were readily taken up by monocytes and neutrophils, and this uptake was partially inhibited by mAb 60.11, which recognizes the C1q binding site on gC1qR. Taken together, the data suggest a role, for gC1qR at least in the initial stages of spore attachment and/or entry.

  2. Structures of Human Cyctochrome P450 2E1: Insights Into the Binding of Inhibitors And Both Small Molecular Weight And Fatty Acid Substrates

    SciTech Connect (OSTI)

    Porubsky, P.R.; Meneely, K.M.; Scott, E.E.

    2009-05-21

    Human microsomal cytochrome P-450 2E1 (CYP2E1) monooxygenates >70 low molecular weight xenobiotic compounds, as well as much larger endogenous fatty acid signaling molecules such as arachidonic acid. In the process, CYP2E1 can generate toxic or carcinogenic compounds, as occurs with acetaminophen overdose, nitrosamines in cigarette smoke, and reactive oxygen species from uncoupled catalysis. Thus, the diverse roles that CYP2E1 has in normal physiology, toxicity, and drug metabolism are related to its ability to metabolize diverse classes of ligands, but the structural basis for this was previously unknown. Structures of human CYP2E1 have been solved to 2.2 {angstrom} for an indazole complex and 2.6 {angstrom} for a 4-methylpyrazole complex. Both inhibitors bind to the heme iron and hydrogen bond to Thr{sup 303} within the active site. Complementing its small molecular weight substrates, the hydrophobic CYP2E1 active site is the smallest yet observed for a human cytochrome P-450. The CYP2E1 active site also has two adjacent voids: one enclosed above the I helix and the other forming a channel to the protein surface. Minor repositioning of the Phe{sup 478} aromatic ring that separates the active site and access channel would allow the carboxylate of fatty acid substrates to interact with conserved {sup 216}QXXNN{sup 220} residues in the access channel while positioning the hydrocarbon terminus in the active site, consistent with experimentally observed {omega}-1 hydroxylation of saturated fatty acids. Thus, these structures provide insights into the ability of CYP2E1 to effectively bind and metabolize both small molecule substrates and fatty acids.

  3. 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.; Alfè, 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 showmore » 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 (B₃N₃H₆) 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

  4. 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.

  5. 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..

  6. The roles of RIIbeta linker and N-terminal cyclic nucleotide-binding domain in determining the unique structures of Type IIbeta Protein Kinase A. A small angle X-ray and neutron scattering study

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

    Blumenthal, Donald K.; Copps, Jeffrey; Smith-Nguyen, Eric V.; Zhang, Ping; Heller, William T.; Taylor, Susan S.

    2014-08-11

    Protein kinase A (PKA) is ubiquitously expressed and is responsible for regulating many important cellular functions in response to changes in intracellular cAMP concentrations. Moreover, the PKA holoenzyme is a tetramer (R2:C2), with a regulatory subunit homodimer (R2) that binds and inhibits two catalytic (C) subunits; binding of cAMP to the regulatory subunit homodimer causes activation of the catalytic subunits. Four different R subunit isoforms exist in mammalian cells, and these confer different structural features, subcellular localization, and biochemical properties upon the PKA holoenzymes they form. The holoenzyme containing RIIβ is structurally unique in that the type IIβ holoenzyme ismore » much more compact than the free RIIβ homodimer. We have used small angle x-ray scattering and small angle neutron scattering to study the solution structure and subunit organization of a holoenzyme containing an RIIβ C-terminal deletion mutant (RIIβ(1–280)), which is missing the C-terminal cAMP-binding domain to better understand the structural organization of the type IIβ holoenzyme and the RIIβ domains that contribute to stabilizing the holoenzyme conformation. These results demonstrate that compaction of the type IIβ holoenzyme does not require the C-terminal cAMP-binding domain but rather involves large structural rearrangements within the linker and N-terminal cyclic nucleotide-binding domain of the RIIβ homodimer. The structural rearrangements are significantly greater than seen previously with RIIα and are likely to be important in mediating short range and long range interdomain and intersubunit interactions that uniquely regulate the activity of the type IIβ isoform of PKA.« less

  7. Theory of the electronic structure of dilute bismide and bismide-nitride alloys of GaAs: Tight-binding and k.p models

    SciTech Connect (OSTI)

    Usman, Muhammad; Broderick, Christopher A.; O'Reilly, Eoin P.

    2013-12-04

    The addition of dilute concentrations of bismuth (Bi) into GaAs to form GaBi{sub x}As{sub 1?x} alloys results in a large reduction of the band gap energy (E{sub g}) accompanied by a significant increase of the spin-orbit-splitting energy (?{sub SO}), leading to an E{sub g} < ?{sub SO} regime for x ? 10% which is technologically relevant for the design of highly efficient photonic devices. The quaternary alloy GaBi{sub x}N{sub y}As{sub 1?x?y} offers further flexibility for band gap tuning, because both nitrogen and bismuth can independently induce band gap reduction. This work reports sp{sup 3}s* tight binding and 14-band k?p models for the study of the electronic structure of GaBi{sub x}As{sub 1?x} and GaBi{sub x}N{sub y}As{sub 1?x?y} alloys. Our results are in good agreement with the available experimental data.

  8. 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.

  9. Study of the Mn-binding sites in photosystem II using antibodies raised against lumenal regions of the D1 and D2 reaction center proteins

    SciTech Connect (OSTI)

    Dalmasso, E.A.

    1992-04-01

    The experiments discussed in this thesis focus on identifying the protein segments or specific amino acids which provide ligands to the Mn cluster of photosystem II (PS II). This Mn cluster plays a central role in the oxygen-evolving complex (OEC) of PS II. The Mn cluster is thought to be bound by lumenal regions of the PS II reaction center proteins known as D1 and D2. First, several peptides were synthesized which correspond to specific lumenal segments of the D1 and D2 proteins. Next, polyclonal antibodies were successfully elicited using three of these peptides. The peptides recognized by these antibodies correspond to protein segments of the spinach reaction center proteins: Ile-321 to Ala-344 of D1 (D1-a), Asp-319 to Arg-334 of D1 (D1-b), and Val-300 to Asn-319 of D2 (D2-a). These antibodies were then used in assays which were developed to structurally or functionally probe the potential Mn-binding regions of the D1 and D2 proteins.

  10. Thermodynamic analysis reveals that GTP binding affects the interaction between the {alpha}- and {gamma}-subunits of translation initiation factor 2

    SciTech Connect (OSTI)

    Nakakido, Makoto; Tanaka, Yoshikazu; Sokabe, Masaaki; Tsumoto, Kouhei

    2008-07-11

    Eukaryotic and archaeal translation initiation factors 2, heterotrimers that consist of {alpha}-, {beta}-, and {gamma}-subunits, deliver methionylated initiator tRNA to a small ribosomal subunit in a manner that depends on GTP. To evaluate correlation of the function and association of the subunits, we used isothermal titration calorimetry to analyze the thermodynamics of the interactions between the {alpha}- and {gamma}-subunits in the presence or absence of a nonhydrolyzable GTP analog or GDP. The {alpha}-subunits bound to the {gamma}-subunit with large heat capacity change ({delta}C{sub p}) values. The {delta}H and {delta}C{sub p} values for the interaction between the {alpha}- and {gamma}-subunits varied in the presence of the GTP analog but not in the presence of GDP. These results suggest that the binding of both the {alpha}-subunit and GTP changes the conformation of the switch region of the {gamma}-subunit and increases the affinity of the {gamma}-subunit for tRNA.

  11. Accumulated SET protein up-regulates and interacts with hnRNPK, increasing its binding to nucleic acids, the Bcl-xS repression, and cellular proliferation

    SciTech Connect (OSTI)

    Almeida, Luciana O.; Garcia, Cristiana B.; Matos-Silva, Flavia A.; Curti, Carlos; Leopoldino, Andria M.

    2014-02-28

    Highlights: hnRNPK is a new target of SET. SET regulates hnRNPK. SET and hnRNPK accumulation promotes tumorigenesis. SET accumulation is a potential model to study genes regulated by SET-hnRNPK. - Abstract: SET and hnRNPK are proteins involved in gene expression and regulation of cellular signaling. We previously demonstrated that SET accumulates in head and neck squamous cell carcinoma (HNSCC); hnRNPK is a prognostic marker in cancer. Here, we postulate that SET and hnRNPK proteins interact to promote tumorigenesis. We performed studies in HEK293 and HNSCC (HN6, HN12, and HN13) cell lines with SET/hnRNPK overexpression and knockdown, respectively. We found that SET and/or hnRNPK protein accumulation increased cellular proliferation. SET accumulation up-regulated hnRNPK mRNA and total/phosphorylated protein, promoted hnRNPK nuclear location, and reduced Bcl-x mRNA levels. SET protein directly interacted with hnRNPK, increasing both its binding to nucleic acids and Bcl-xS repression. We propose that hnRNPK should be a new target of SET and that SEThnRNPK interaction, in turn, has potential implications in cell survival and malignant transformation.

  12. How Dynein Binds to Microtubules

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

    energy stored in adenosine triphosphate (ATP) molecules into mechanical work. Some motor proteins, such as myosin, are found in muscle fibers, and their functioning ultimately...

  13. How Dynein Binds to Microtubules

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

    Motor proteins are excellent examples of "nanotechnology" in Nature. These fascinating protein molecules convert the chemical energy stored in adenosine triphosphate (ATP)...

  14. BPA FINAL Binding Arbitration policy

    Broader source: Energy.gov [DOE]

    Alternative dispute resolution (ADR) encompasses a variety of methods that parties may use to resolve disputes without litigation. Arbitration is a private, less formal process in which parties...

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. Design of HIV-1 Protease Inhibitors with Amino-bis-tetrahydrofuran Derivatives as P2-Ligands to Enhance Backbone-Binding Interactions. Synthesis, Biological Evaluation, and Protein-Ligand X-ray Studies

    SciTech Connect (OSTI)

    Ghosh, Arun K.; Martyr, Cuthbert D.; Osswald, Heather L.; Sheri, Venkat Reddy; Kassekert, Luke A.; Chen, Shujing; Agniswamy, Johnson; Wang, Yuan-Fang; Hayashi, Hironori; Aoki, Manabu; Weber, Irene T.; Mitsuya, Hiroaki

    2015-10-30

    Structure-based design, synthesis, and biological evaluation of a series of very potent HIV-1 protease inhibitors are described. In an effort to improve backbone ligandbinding site interactions, we have incorporated basic-amines at the C4 position of the bis-tetrahydrofuran (bis-THF) ring. We speculated that these substituents would make hydrogen bonding interactions in the flap region of HIV-1 protease. Synthesis of these inhibitors was performed diastereoselectively. A number of inhibitors displayed very potent enzyme inhibitory and antiviral activity. Inhibitors 25f, 25i, and 25j were evaluated against a number of highly-PI-resistant HIV-1 strains, and they exhibited improved antiviral activity over darunavir. Two high resolution X-ray structures of 25f- and 25g-bound HIV-1 protease revealed unique hydrogen bonding interactions with the backbone carbonyl group of Gly48 as well as with the backbone NH of Gly48 in the flap region of the enzyme active site. These ligandbinding site interactions are possibly responsible for their potent activity.

  1. Privacy Act Advisory | U.S. DOE Office of Science (SC)

    Office of Science (SC) Website

    Privacy Act Advisory Integrated Support Center (ISC) ISC Home About Services Freedom of Information Act (FOIA) Privacy Act Advisory Exemptions How to Submit a FOIA Request Fee Waiver and Reduction Criteria Electronic Reading Room ISC Conventional Reading Rooms Reference Links Privacy Act NEPA Documents Contact Information Integrated Support Center Roxanne Purucker U.S. Department of Energy 9800 S. Cass Avenue Argonne, IL 60439 P: (630) 252-2110 Don F. Thress, Jr. U.S. Department of Energy 200

  2. Reference Links | U.S. DOE Office of Science (SC)

    Office of Science (SC) Website

    Reference Links Integrated Support Center (ISC) ISC Home About Services Freedom of Information Act (FOIA) Privacy Act Advisory Exemptions How to Submit a FOIA Request Fee Waiver and Reduction Criteria Electronic Reading Room ISC Conventional Reading Rooms Reference Links Privacy Act NEPA Documents Contact Information Integrated Support Center Roxanne Purucker U.S. Department of Energy 9800 S. Cass Avenue Argonne, IL 60439 P: (630) 252-2110 Don F. Thress, Jr. U.S. Department of Energy 200

  3. Exemptions | U.S. DOE Office of Science (SC)

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

    Exemptions Integrated Support Center (ISC) ISC Home About Services Freedom of Information Act (FOIA) Privacy Act Advisory Exemptions How to Submit a FOIA Request Fee Waiver and Reduction Criteria Electronic Reading Room ISC Conventional Reading Rooms Reference Links Privacy Act NEPA Documents Contact Information Integrated Support Center Roxanne Purucker U.S. Department of Energy 9800 S. Cass Avenue Argonne, IL 60439 P: (630) 252-2110 Don F. Thress, Jr. U.S. Department of Energy 200

  4. FOIA Request Form | U.S. DOE Office of Science (SC)

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

    How to Submit a FOIA Request » FOIA Request Form Integrated Support Center (ISC) ISC Home About Services Freedom of Information Act (FOIA) Privacy Act Advisory Exemptions How to Submit a FOIA Request FOIA Request Form Fee Waiver and Reduction Criteria Electronic Reading Room ISC Conventional Reading Rooms Reference Links Privacy Act NEPA Documents Contact Information Integrated Support Center Roxanne Purucker U.S. Department of Energy 9800 S. Cass Avenue Argonne, IL 60439 P: (630) 252-2110 Don

  5. Fee Waiver and Reduction Criteria | U.S. DOE Office of Science (SC)

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

    Fee Waiver and Reduction Criteria Integrated Support Center (ISC) ISC Home About Services Freedom of Information Act (FOIA) Privacy Act Advisory Exemptions How to Submit a FOIA Request Fee Waiver and Reduction Criteria Electronic Reading Room ISC Conventional Reading Rooms Reference Links Privacy Act NEPA Documents Contact Information Integrated Support Center Roxanne Purucker U.S. Department of Energy 9800 S. Cass Avenue Argonne, IL 60439 P: (630) 252-2110 Don F. Thress, Jr. U.S. Department of

  6. CRF

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

    CRF Home/CRF - Jackie Chen talking Permalink Gallery Jackie Chen to give keynote address at ISC High performance conference in Germany CRF, News, Transportation Energy, Uncategorized Jackie Chen to give keynote address at ISC High performance conference in Germany By Michael Padilla Jackie Chen, distinguished member of technical staff at the Combustion Research Facility, is scheduled to deliver the keynote address on Tuesday, June 21, at the ISC High Performance conference in Frankfurt, Germany.

  7. China-Partnership for Climate Action | Open Energy Information

    Open Energy Info (EERE)

    Jump to: navigation, search Name Partnership for Climate Action - China AgencyCompany Organization Institute for Sustainable Communities (ISC) Partner World Resources Institute...

  8. 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

    SciTech Connect (OSTI)

    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 epitope peptide 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.

  9. 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.

  10. 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 epitopemore » peptide 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

  11. 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.

  12. 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.

  13. Method of identity analyte-binding peptides

    DOE Patents [OSTI]

    Kauvar, Lawrence M. (San Francisco, CA)

    1990-01-01

    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.

  14. 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.

  15. Critical interpretation of CH and OH stretching regions for infrared spectra of methanol clusters (CH{sub 3}OH){sub n} (n = 25) using self-consistent-charge density functional tight-binding molecular dynamics simulations

    SciTech Connect (OSTI)

    Nishimura, Yoshifumi; Lee, Yuan-Pern; Irle, Stephan; Witek, Henryk A.

    2014-09-07

    Vibrational infrared (IR) spectra of gas-phase OH???O methanol clusters up to pentamer are simulated using self-consistent-charge density functional tight-binding method using two distinct methodologies: standard normal mode analysis and Fourier transform of the dipole time-correlation function. The twofold simulations aim at the direct critical assignment of the CH stretching region of the recently recorded experimental spectra [H.-L. Han, C. Camacho, H. A. Witek, and Y.-P. Lee, J. Chem. Phys. 134, 144309 (2011)]. Both approaches confirm the previous assignment (ibid.) of the CH stretching bands based on the B3LYP/ANO1 harmonic frequencies, showing that ?{sub 3}, ?{sub 9}, and ?{sub 2} CH stretching modes of the proton-accepting (PA) and proton-donating (PD) methanol monomers experience only small splittings upon the cluster formation. This finding is in sharp discord with the assignment based on anharmonic B3LYP/VPT2/ANO1 vibrational frequencies (ibid.), suggesting that some procedural faults, likely related to the breakdown of the perturbational vibrational treatment, led the anharmonic calculations astray. The IR spectra based on the Fourier transform of the dipole time-correlation function include new, previously unaccounted for physical factors such as non-zero temperature of the system and large amplitude motions of the clusters. The elevation of temperature results in a considerable non-homogeneous broadening of the observed IR signals, while the presence of large-amplitude motions (methyl group rotations and PA-PD flipping), somewhat surprisingly, does not introduce any new features in the spectrum.

  16. Structures of Pseudomonas aeruginosa ?-ketoacyl-(acyl-carrier-protein) synthase II (FabF) and a C164Q mutant provide templates for antibacterial drug discovery and identify a buried potassium ion and a ligand-binding site that is an artefact of the crystal form

    SciTech Connect (OSTI)

    Baum, Bernhard; Lecker, Laura S. M.; Zoltner, Martin; Jaenicke, Elmar; Schnell, Robert; Hunter, William N.; Brenk, Ruth

    2015-07-28

    Three crystal structures of recombinant P. aeruginosa FabF are reported: the apoenzyme, an active-site mutant and a complex with a fragment of a natural product inhibitor. The characterization provides reagents and new information to support antibacterial drug discovery. Bacterial infections remain a serious health concern, in particular causing life-threatening infections of hospitalized and immunocompromised patients. The situation is exacerbated by the rise in antibacterial drug resistance, and new treatments are urgently sought. In this endeavour, accurate structures of molecular targets can support early-stage drug discovery. Here, crystal structures, in three distinct forms, of recombinant Pseudomonas aeruginosa ?-ketoacyl-(acyl-carrier-protein) synthase II (FabF) are presented. This enzyme, which is involved in fatty-acid biosynthesis, has been validated by genetic and chemical means as an antibiotic target in Gram-positive bacteria and represents a potential target in Gram-negative bacteria. The structures of apo FabF, of a C164Q mutant in which the binding site is altered to resemble the substrate-bound state and of a complex with 3-(benzoylamino)-2-hydroxybenzoic acid are reported. This compound mimics aspects of a known natural product inhibitor, platensimycin, and surprisingly was observed binding outside the active site, interacting with a symmetry-related molecule. An unusual feature is a completely buried potassium-binding site that was identified in all three structures. Comparisons suggest that this may represent a conserved structural feature of FabF relevant to fold stability. The new structures provide templates for structure-based ligand design and, together with the protocols and reagents, may underpin a target-based drug-discovery project for urgently needed antibacterials.

  17. Personal Property Management | U.S. DOE Office of Science (SC)

    Office of Science (SC) Website

    Personal Property Management Integrated Support Center (ISC) ISC Home About Services Freedom of Information Act (FOIA) Privacy Act NEPA Documents Contact Information Integrated Support Center Roxanne Purucker U.S. Department of Energy 9800 S. Cass Avenue Argonne, IL 60439 P: (630) 252-2110 Don F. Thress, Jr. U.S. Department of Energy 200 Administration Road Oak Ridge, TN 37830 P: (865) 576-4444 Services Personal Property Management Print Text Size: A A A FeedbackShare Page The ISC's Personal

  18. Quality Management | U.S. DOE Office of Science (SC)

    Office of Science (SC) Website

    Quality Management Integrated Support Center (ISC) ISC Home About Services Freedom of Information Act (FOIA) Privacy Act NEPA Documents Contact Information Integrated Support Center Roxanne Purucker U.S. Department of Energy 9800 S. Cass Avenue Argonne, IL 60439 P: (630) 252-2110 Don F. Thress, Jr. U.S. Department of Energy 200 Administration Road Oak Ridge, TN 37830 P: (865) 576-4444 Services Quality Management Print Text Size: A A A FeedbackShare Page The ISC provides quality assurance

  19. Jobs | U.S. DOE Office of Science (SC)

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

    About » Jobs Integrated Support Center (ISC) ISC Home About Jobs Services Freedom of Information Act (FOIA) Privacy Act NEPA Documents Contact Information Integrated Support Center Roxanne Purucker U.S. Department of Energy 9800 S. Cass Avenue Argonne, IL 60439 P: (630) 252-2110 Don F. Thress, Jr. U.S. Department of Energy 200 Administration Road Oak Ridge, TN 37830 P: (865) 576-4444 About Jobs Print Text Size: A A A Subscribe FeedbackShare Page Current Open Federal Positions The ISC is a

  20. An accurate and efficient computational protocol for obtaining the complete basis set limits of the binding energies of water clusters at the MP2 and CCSD(T) levels of theory: Application to (H?O)m, m=2-6, 8, 11, 16 and 17

    SciTech Connect (OSTI)

    Miliordos, Evangelos; Xantheas, Sotiris S.

    2015-06-21

    We report MP2 and CCSD(T) binding energies with basis sets up to pentuple zeta quality for the m = 2-6, 8 clusters. Or best CCSD(T)/CBS estimates are -4.99 kcal/mol (dimer), -15.77 kcal/mol (trimer), -27.39 kcal/mol (tetramer), -35.9 0.3 kcal/mol (pentamer), -46.2 0.3 kcal/mol (prism hexamer), -45.9 0.3 kcal/mol (cage hexamer), -45.4 0.3 kcal/mol (book hexamer), -44.3 0.3 kcal/mol (ring hexamer), -73.0 0.5 kcal/mol (D2d octamer) and -72.9 0.5 kcal/mol (S4 octamer). We have found that the percentage of both the uncorrected (dimer) and BSSE-corrected (dimerCPe) binding energies recovered with respect to the CBS limit falls into a narrow range for each basis set for all clusters and in addition this range was found to decrease upon increasing the basis set. Relatively accurate estimates (within < 0.5%) of the CBS limits can be obtained when using the 2/3, 1/3 (for the AVDZ set) or the , (for the AVTZ, AVQZ and AV5Z sets) mixing ratio between dimere and dimerCPe. Based on those findings we propose an accurate and efficient computational protocol that can be used to estimate accurate binding energies of clusters at the MP2 (for up to 100 molecules) and CCSD(T) (for up to 30 molecules) levels of theory. This work was supported by the US Department of Energy, Office of Science, Office of Basic Energy Sciences, Division of Chemical Sciences, Geosciences and Biosciences. Pacific Northwest National Laboratory (PNNL) is a multi program national laboratory operated for DOE by Battelle. This research also used resources of the National Energy Research Scientific Computing Center, which is supported by the Office of Science of the U.S. Department of Energy under Contract No. AC02-05CH11231.

  1. Improved algorithms for estimating the effects of pollution impacts from area and open pit sources

    SciTech Connect (OSTI)

    Petersen, W.B.; Perry, S.G.

    1995-11-01

    Title II, Part B, Section 234 of the Clean Air Act Amendments of 1990 provide for a reexamination of the current Environmental Protection Agency`s methods for modeling fugitive particulate (PM10) from open-pit surface coal mines. ISC2 is specifically named as the method that needs further study. To address the requirements of the Act, an open pit algorithm has been developed. The algorithm uses the pit depth and dimensions, height of emissions above the pit floor, and the wind direction to (1) estimate the fraction of particulate that leaves the pit (escape fraction) and (2) to calculate the sub-area dimensions. Although the development work for the area source and open pit algorithms was done with ISC2, both are incorporated in ISC3. In this paper the authors will refer to the model incorporating these algorithms as ISC3.

  2. 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...

  3. CX-010766: Categorical Exclusion Determination

    Broader source: Energy.gov [DOE]

    Interim Storage Area for Interim Storage Containers (ISCs) at the Radioactive Scrap and Waste Facility (RSWF) CX(s) Applied: B6.6 Date: 08/16/2013 Location(s): Idaho Offices(s): Nuclear Energy

  4. Sandia Energy - Test and Evaluation

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

    such as thin films, advanced inverters, and CPV. For example, the lab can customize its multi-sun tester to characterize CPV cells with an Isc less than 1 Amp, and can accommodate...

  5. PowerPoint Presentation

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

    Coding for the Future: Knights Landing and beyond CJ Newburn, SW/HW HPC Architect, . Community Builder July 16, 2015 ISC15 IXPUG Workshop: The Road to Application Performance on Intel® Xeon Phi(tm) Coprocessor Copyright © 2015, Intel Corporation. All rights reserved. Chris J. Newburn (CJ), ISC15 IXPUG Workshop Optimization Notice Outline A plan for optimization Trends that are here to stay New features that involve SW enabling How development tools help How analysis tools help Manual steps

  6. Microsoft Word - DOE-ID-INL-13-020.doc

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

    0 SECTION A. Project Title: Interim Storage Area for Interim Storage Containers (ISCs) at the Radioactive Scrap and Waste Facility (RSWF) SECTION B. Project Description: Currently, dedicated space is unavailable for above-grade storage of Interim Storage Containers (ISCs) containing 55-gal drums of remote handled transuranic waste (RH-TRU). In the past this waste was packaged in specially constructed liners and placed into the RSWF. When ready for transfer this waste would then be removed from

  7. Privacy Act | U.S. DOE Office of Science (SC)

    Office of Science (SC) Website

    Privacy Act Integrated Support Center (ISC) ISC Home About Services Freedom of Information Act (FOIA) Privacy Act Compilation of Systems of Records Energy Employees Occupational Illness Compensation Program Act (EEOICPA) How to Submit a Privacy Act Request Reference Links NEPA Documents Contact Information Integrated Support Center Roxanne Purucker U.S. Department of Energy 9800 S. Cass Avenue Argonne, IL 60439 P: (630) 252-2110 Don F. Thress, Jr. U.S. Department of Energy 200 Administration

  8. Compilation of Systems of Records | U.S. DOE Office of Science (SC)

    Office of Science (SC) Website

    Compilation of Systems of Records Integrated Support Center (ISC) ISC Home About Services Freedom of Information Act (FOIA) Privacy Act Compilation of Systems of Records Energy Employees Occupational Illness Compensation Program Act (EEOICPA) How to Submit a Privacy Act Request Reference Links NEPA Documents Contact Information Integrated Support Center Roxanne Purucker U.S. Department of Energy 9800 S. Cass Avenue Argonne, IL 60439 P: (630) 252-2110 Don F. Thress, Jr. U.S. Department of Energy

  9. Public Affairs and Intergovernmental Relations | U.S. DOE Office of Science

    Office of Science (SC) Website

    (SC) Public Affairs and Intergovernmental Relations Integrated Support Center (ISC) ISC Home About Services Freedom of Information Act (FOIA) Privacy Act NEPA Documents Contact Information Integrated Support Center Roxanne Purucker U.S. Department of Energy 9800 S. Cass Avenue Argonne, IL 60439 P: (630) 252-2110 Don F. Thress, Jr. U.S. Department of Energy 200 Administration Road Oak Ridge, TN 37830 P: (865) 576-4444 Services Public Affairs and Intergovernmental Relations Print Text Size: A

  10. Reservation Management | U.S. DOE Office of Science (SC)

    Office of Science (SC) Website

    Reservation Management Integrated Support Center (ISC) ISC Home About Services Freedom of Information Act (FOIA) Privacy Act NEPA Documents Contact Information Integrated Support Center Roxanne Purucker U.S. Department of Energy 9800 S. Cass Avenue Argonne, IL 60439 P: (630) 252-2110 Don F. Thress, Jr. U.S. Department of Energy 200 Administration Road Oak Ridge, TN 37830 P: (865) 576-4444 Services Reservation Management Print Text Size: A A A FeedbackShare Page Related Links Emergency

  11. NREL Innovation Improves Safety of Electric Vehicle Batteries - News

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

    Feature | NREL Innovation Improves Safety of Electric Vehicle Batteries October 30, 2015 A man holds a sheet of copper discs. NREL Senior Engineer Mathew Keyser holds a sheet of copper discs, one of the metal components that comprise the NREL Internal Short Circuit (ISC) device, capable of emulating latent defects that can cause escalating temperatures in lithium ion batteries and lead to thermal runaway. Industry can use the NREL ISC device to evaluate solutions intended to address this

  12. Information Management | U.S. DOE Office of Science (SC)

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

    Information Management Integrated Support Center (ISC) ISC Home About Services Freedom of Information Act (FOIA) Privacy Act NEPA Documents Contact Information Integrated Support Center Roxanne Purucker U.S. Department of Energy 9800 S. Cass Avenue Argonne, IL 60439 P: (630) 252-2110 Don F. Thress, Jr. U.S. Department of Energy 200 Administration Road Oak Ridge, TN 37830 P: (865) 576-4444 Services Information Management Print Text Size: A A A FeedbackShare Page Integrated Support Center

  13. Phosphoprotein binding agents and methods of their use

    DOE Patents [OSTI]

    Goshe, Michael B.; Conrads, Thomas P.; Veenstra, Timothy D.; Panisko, Ellen A.

    2004-11-16

    The invention provides reagents and methods for characterizing (i.e., identification and/or quantitation) the phosphorylation states of proteins. Proteins may be post-transcriptionally modified such that they contain phosphate groups at either some or all of their serine, threonine, tyrosine, histidine, and/or lysine amino acid residues. In many cases the extent to which a protein is phosphorylated determines it bioactivity, i.e., its ability to effect cell functions such as differentiation, division, and metabolism. Hence, a powerful tool for diagnosing various diseases and for furthering the understanding of protein--protein interactions is provided.

  14. DNA-Binding Mechanism in Prokaryotic Partition Complex Formation

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

    other invaders from outside our bodies can be deadly foes that bring disease and death. In either case, understanding how bacteria multiply and grow not only increases our...

  15. Briefly Bound to Activate: Transient Binding of a Second Catalytic...

    Office of Scientific and Technical Information (OSTI)

    Authors: Bao, Zhao Qin ; Jacobsen, Douglas M. ; Young, Matthew A. 1 + Show Author Affiliations (Michigan-Med) Publication Date: 2014-10-02 OSTI Identifier: 1031377 Resource Type: ...

  16. Electrical Tuning of Exciton Binding Energies in Monolayer WS...

    Office of Scientific and Technical Information (OSTI)

    Date: 2015-09-16 OSTI Identifier: 1215790 Type: Publisher's Accepted Manuscript Journal Name: Physical Review Letters Additional Journal Information: Journal Volume: 115;...

  17. Structural Basis of Wnt Signaling Inhibition by Dickkopf Binding...

    Office of Scientific and Technical Information (OSTI)

    Additional Journal Information: Journal Volume: 21; Journal Issue: 5; Journal ID: ISSN 1534-5807 Publisher: Elsevier Sponsoring Org: USDOE Country of Publication: Country unknown...

  18. Boron compounds as anion binding agents for nonaqueous battery electrolytes

    DOE Patents [OSTI]

    Lee, Hung Sui (East Setauket, NY); Yang, Xia-Oing (Port Jefferson Station, NY); McBreen, James (Bellport, NY); Xiang, Caili (Upton, NY)

    2000-02-08

    Novel fluorinated boron-based compounds which act as anion receptors in non-aqueous battery electrolytes are provided. When added to non-aqueous battery electrolytes, the fluorinated boron-based compounds of the invention enhance ionic conductivity and cation transference number of non-aqueous electrolytes. The fluorinated boron-based anion receptors include borane and borate compounds bearing different fluorinated alkyl and aryl groups.

  19. DNA polymerase having modified nucleotide binding site for DNA sequencing

    DOE Patents [OSTI]

    Tabor, S.; Richardson, C.

    1997-03-25

    A modified gene encoding a modified DNA polymerase is disclosed. The modified polymerase incorporates dideoxynucleotides at least 20-fold better compared to the corresponding deoxynucleotides as compared with the corresponding naturally-occurring DNA polymerase. 6 figs.

  20. DNA polymerase having modified nucleotide binding site for DNA sequencing

    DOE Patents [OSTI]

    Tabor, Stanley; Richardson, Charles

    1997-01-01

    Modified gene encoding a modified DNA polymerase wherein the modified polymerase incorporates dideoxynucleotides at least 20-fold better compared to the corresponding deoxynucleotides as compared with the corresponding naturally-occurring DNA polymerase.

  1. Probing Product Binding in Cellulase Enzymes (Fact Sheet)

    SciTech Connect (OSTI)

    Not Available

    2012-08-01

    Simulations uncover potential new strategies for increasing the desired effects of enzymes for biofuels.

  2. Visually Relating Gene Expression and in vivo DNA Binding Data...

    Office of Scientific and Technical Information (OSTI)

    Number: DE-AC02-05CH11231 Resource Type: Conference Resource Relation: Conference: IEEE International Conference on Bioinformatics and Biomedicine 2011 (IEEE BIBM 2011)...

  3. Characterization of Selective Binding of Alkali Cations with...

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

    x-rays, such as provided by the ALS. The team's measurements indicated carboxylate groups characteristic of proteins preferred sodium over potassium ions. These results lend...

  4. Paul D. Boyer, Adenosine Triphosphate (ATP), and the Binding...

    Office of Scientific and Technical Information (OSTI)

    Using Walker's methodology, one of Boyer's former graduate students "did some elegant ... Boyer Award Lecture Series, University of Wisconsin Journey Page 2, research at UCLA Paul ...

  5. A Novel Mechanism for Binding of Galactose-terminated Glycans...

    Office of Scientific and Technical Information (OSTI)

    Resource Type: Journal Article Resource Relation: Journal Name: J. Biol. Chem.; Journal Volume: 290; Journal Issue: (27) ; 07, 2015 Research Org: Advanced Photon Source (APS), ...

  6. Memo Is Homologous to Nonheme Iron Dioxygenases and Binds an...

    Office of Scientific and Technical Information (OSTI)

    Resource Type: Journal Article Resource Relation: Journal Name: J. Biol. Chem.; Journal Volume: 283; Journal Issue: (5) ; 02, 2008 Research Org: Advanced Photon Source (APS), ...

  7. Visually Relating Gene Expression and in vivo DNA Binding Data...

    Office of Scientific and Technical Information (OSTI)

    analysis tools exist for each data type alone, there is a lack of tools that can easily explore the relationship between them. We propose an approach that uses the average...

  8. Defining How Botulinum Toxin Binds to the Synaptotagmin Receptor...

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

    II (Syt-II) recognition domain (1) and botulinum toxin with two different neutralizing monoclonal antibodies (2). To compliment the structural work, biochemical, mutagenesis,...

  9. Binding Behavior of Dopamine Transporter Key to Understanding...

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

    Understanding Chemical Reactions in the Brain Print Most people have heard of ... What most people do not know is that the same receptors in the human brain recognize the ...

  10. Services | U.S. DOE Office of Science (SC)

    Office of Science (SC) Website

    Services Integrated Support Center (ISC) ISC Home About Services Freedom of Information Act (FOIA) Privacy Act NEPA Documents Contact Information Integrated Support Center Roxanne Purucker U.S. Department of Energy 9800 S. Cass Avenue Argonne, IL 60439 P: (630) 252-2110 Don F. Thress, Jr. U.S. Department of Energy 200 Administration Road Oak Ridge, TN 37830 P: (865) 576-4444 Services Print Text Size: A A A FeedbackShare Page Service Plan of the SC Integrated Support Center .pdf file (410KB)

  11. Environment, Safety and Health (ES&H) | U.S. DOE Office of Science (SC)

    Office of Science (SC) Website

    Environment, Safety and Health (ES&H) Integrated Support Center (ISC) ISC Home About Services Freedom of Information Act (FOIA) Privacy Act NEPA Documents Contact Information Integrated Support Center Roxanne Purucker U.S. Department of Energy 9800 S. Cass Avenue Argonne, IL 60439 P: (630) 252-2110 Don F. Thress, Jr. U.S. Department of Energy 200 Administration Road Oak Ridge, TN 37830 P: (865) 576-4444 Services Environment, Safety and Health (ES&H) Print Text Size: A A A FeedbackShare

  12. Real Property Management | U.S. DOE Office of Science (SC)

    Office of Science (SC) Website

    Real Property Management Integrated Support Center (ISC) ISC Home About Services Freedom of Information Act (FOIA) Privacy Act NEPA Documents Contact Information Integrated Support Center Roxanne Purucker U.S. Department of Energy 9800 S. Cass Avenue Argonne, IL 60439 P: (630) 252-2110 Don F. Thress, Jr. U.S. Department of Energy 200 Administration Road Oak Ridge, TN 37830 P: (865) 576-4444 Services Real Property Management Print Text Size: A A A FeedbackShare Page Real Property Management

  13. Safeguards & Security | U.S. DOE Office of Science (SC)

    Office of Science (SC) Website

    Safeguards & Security Integrated Support Center (ISC) ISC Home About Services Freedom of Information Act (FOIA) Privacy Act NEPA Documents Contact Information Integrated Support Center Roxanne Purucker U.S. Department of Energy 9800 S. Cass Avenue Argonne, IL 60439 P: (630) 252-2110 Don F. Thress, Jr. U.S. Department of Energy 200 Administration Road Oak Ridge, TN 37830 P: (865) 576-4444 Services Safeguards & Security Print Text Size: A A A FeedbackShare Page Security and Emergency

  14. Small Business Program Management | U.S. DOE Office of Science (SC)

    Office of Science (SC) Website

    Small Business Program Management Integrated Support Center (ISC) ISC Home About Services Freedom of Information Act (FOIA) Privacy Act NEPA Documents Contact Information Integrated Support Center Roxanne Purucker U.S. Department of Energy 9800 S. Cass Avenue Argonne, IL 60439 P: (630) 252-2110 Don F. Thress, Jr. U.S. Department of Energy 200 Administration Road Oak Ridge, TN 37830 P: (865) 576-4444 Services Small Business Program Management Print Text Size: A A A FeedbackShare Page Related

  15. Contractor Human Resources | U.S. DOE Office of Science (SC)

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

    Contractor Human Resources Integrated Support Center (ISC) ISC Home About Services Freedom of Information Act (FOIA) Privacy Act NEPA Documents Contact Information Integrated Support Center Roxanne Purucker U.S. Department of Energy 9800 S. Cass Avenue Argonne, IL 60439 P: (630) 252-2110 Don F. Thress, Jr. U.S. Department of Energy 200 Administration Road Oak Ridge, TN 37830 P: (865) 576-4444 Services Contractor Human Resources Print Text Size: A A A FeedbackShare Page Contractor Human Resources

  16. Major Contracts Awarded | U.S. DOE Office of Science (SC)

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

    Major Contracts Awarded Integrated Support Center (ISC) ISC Home About Services Freedom of Information Act (FOIA) Privacy Act NEPA Documents Contact Information Integrated Support Center Roxanne Purucker U.S. Department of Energy 9800 S. Cass Avenue Argonne, IL 60439 P: (630) 252-2110 Don F. Thress, Jr. U.S. Department of Energy 200 Administration Road Oak Ridge, TN 37830 P: (865) 576-4444 Acquisition and Assistance Major Contracts Awarded Print Text Size: A A A FeedbackShare Page « Return to

  17. Management and Operating (M&O) Contracts | U.S. DOE Office of Science (SC)

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

    Management and Operating (M&O) Contracts Integrated Support Center (ISC) ISC Home About Services Freedom of Information Act (FOIA) Privacy Act NEPA Documents Contact Information Integrated Support Center Roxanne Purucker U.S. Department of Energy 9800 S. Cass Avenue Argonne, IL 60439 P: (630) 252-2110 Don F. Thress, Jr. U.S. Department of Energy 200 Administration Road Oak Ridge, TN 37830 P: (865) 576-4444 Acquisition and Assistance Management and Operating (M&O) Contracts Print Text

  18. Cori Training

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

    Training Cori Training Intel OpenMP Training @ NERSC Key Actions for Optimizing KNL Performance Tuning and Functional Debugging for Xeon-Phi OpenMP and Vectorization Training IXPUG ISC15 Documents Last edited: 2015-04-28 00:10:29

  19. PROJECT PROFILE: Institute for Sustainable Communities (Solar Market Pathways)

    Broader source: Energy.gov [DOE]

    As the National Coordinator for the SunShot Initiative’s Solar Market Pathways program, the Institute for Sustainable Communities (ISC) will create a learning network that enables communications, coordination and shared learning across the other 14 organizations in the program.

  20. A 5;#8242; cytosine binding pocket in Puf3p specifies regulation...

    Office of Scientific and Technical Information (OSTI)

    Argonne, IL (US) Sponsoring Org: NIH Country of Publication: United States Language: ENGLISH Word Cloud More Like This Full Text Journal Articles DOI: 10.1073pnas.0812079106...

  1. Structures of Minimal Catalytic Fragments of Topoisomerase V Reveals Conformational Changes Relevant for DNA Binding

    SciTech Connect (OSTI)

    Rajan, Rakhi; Taneja, Bhupesh; Mondragn, Alfonso

    2010-12-03

    Topoisomerase V is an archaeal type I topoisomerase that is unique among topoisomerases due to presence of both topoisomerase and DNA repair activities in the same protein. It is organized as an N-terminal topoisomerase domain followed by 24 tandem helix-hairpin-helix (HhH) motifs. Structural studies have shown that the active site is buried by the (HhH) motifs. Here we show that the N-terminal domain can relax DNA in the absence of any HhH motifs and that the HhH motifs are required for stable protein-DNA complex formation. Crystal structures of various topoisomerase V fragments show changes in the relative orientation of the domains mediated by a long bent linker helix, and these movements are essential for the DNA to enter the active site. Phosphate ions bound to the protein near the active site helped model DNA in the topoisomerase domain and show how topoisomerase V may interact with DNA.

  2. The semi-empirical tight-binding model for carbon allotropes between diamond and graphite

    SciTech Connect (OSTI)

    Lytovchenko, V.; Kurchak, A.; Strikha, M.

    2014-06-28

    The new carbon allotropes between diamond and graphite have come under intensive examination during the last decade due to their numerous technical applications. The modification of energy gap in thin films of these allotropes was studied experimentally using optical methods. The proposed simple model of carbon clusters with variable lengths of chemical bonds allows us to imitate the transfer from diamond and diamond-like to graphite-like structures, as well as the corresponding modification of hybridization sp{sup 3}/sp{sup 2} for diamond-like and sp{sub z} for graphite-like phases. This enables us to estimate various allotropes parameters, like the gap E{sub g}, energies of valence E{sub v}, and conduction E{sub c} band edges, and the value of electronic affinity, i.e., optical work function X, which are all of practical importance. The obtained estimations correspond to the experimental data.

  3. Methods for enhancing the degradation of cellulosic material with chitin binding proteins

    DOE Patents [OSTI]

    Xu, Feng

    2015-08-25

    The present invention relates to methods for degrading or converting a cellulosic material and for producing substances from the cellulosic material.

  4. Methods for enhancing the degradation of cellulosic material with chitin binding proteins

    DOE Patents [OSTI]

    Xu, Feng

    2015-03-31

    The present invention relates to methods for degrading or converting a cellulosic material and for producing substances from the cellulosic material.

  5. Reversible CO-binding to the Active Site of Nitrogenase | Stanford...

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

    reaction. A common factor for all these "N2-fixing" systems is that only a single enzyme has apparently emerged that is capable of catalyzing this reduction. The biological...

  6. V-204: A specially crafted query can cause BIND to terminate...

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

    affected source distributions may crash with assertion failures triggered in the same fashion. IMPACT: A specially crafted DNS query could cause the DNS service to terminate...

  7. The same pocket in menin binds both MLL and JUND but has opposite...

    Office of Scientific and Technical Information (OSTI)

    Menin is a tumour suppressor protein whose loss or inactivation causes multiple endocrine ... Menin also interacts with mixed lineage leukaemia protein 1 (MLL1), a histone H3 lysine 4 ...

  8. Force transduction and lipid binding in MscL: A continuum-molecular approach

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

    Vanegas, Juan M.; Arroyo, Marino; Fotiadis, Dimitrios

    2014-12-01

    The bacterial mechanosensitive channel MscL, a small protein mainly activated by membrane tension, is a central model system to study the transduction of mechanical stimuli into chemical signals. Mutagenic studies suggest that MscL gating strongly depends on both intra-protein and interfacial lipid-protein interactions. However, there is a gap between this detailed chemical information and current mechanical models of MscL gating. Here, we investigate the MscL bilayer-protein interface through molecular dynamics simulations, and take a combined continuum-molecular approach to connect chemistry and mechanics. We quantify the effect of membrane tension on the forces acting on the surface of the channel, andmore » identify interactions that may be critical in the force transduction between the membrane and MscL. We find that the local stress distribution on the protein surface is largely asymmetric, particularly under tension, with the cytoplasmic side showing significantly larger and more localized forces, which pull the protein radially outward. The molecular interactions that mediate this behavior arise from hydrogen bonds between the electronegative oxygens in the lipid headgroup and a cluster of positively charged lysine residues on the amphipathic S1 domain and the C-terminal end of the second trans-membrane helix. We take advantage of this strong interaction (estimated to be 10–13 kT per lipid) to actuate the channel (by applying forces on protein-bound lipids) and explore its sensitivity to the pulling magnitude and direction. We conclude by highlighting the simple motif that confers MscL with strong anchoring to the bilayer, and its presence in various integral membrane proteins including the human mechanosensitive channel K2P1 and bovine rhodopsin.« less

  9. Surface Binding and Organization of Sensitizing Dyes on Metal Oxide Single Crystal Surfaces

    SciTech Connect (OSTI)

    Parkinson, Bruce

    2010-06-04

    Even though investigations of dye-sensitized nanocrystalline semiconductors in solar cells has dominated research on dye-sensitized semiconductors over the past two decades. Single crystal electrodes represent far simpler model systems for studying the sensitization process with a continuing train of studies dating back more than forty years. Even today single crystal surfaces prove to be more controlled experimental models for the study of dye-sensitized semiconductors than the nanocrystalline substrates. We analyzed the scientific advances in the model sensitized single crystal systems that preceded the introduction of nanocrystalline semiconductor electrodes. It then follows the single crystal research to the present, illustrating both their striking simplicity of use and clarity of interpretation relative to nanocrystalline electrodes. Researchers have employed many electrochemical, photochemical and scanning probe techniques for studying monolayer quantities of sensitizing dyes at specific crystallographic faces of different semiconductors. These methods include photochronocoulometry, electronic spectroscopy and flash photolysis of dyes at potential-controlled semiconductor electrodes and the use of total internal reflection methods. In addition, we describe the preparation of surfaces of single crystal SnS2 and TiO2 electrodes to serve as reproducible model systems for charge separation at dye sensitized solar cells. This process involves cleaving the SnS2 electrodes and a photoelectrochemical surface treatment for TiO2 that produces clean surfaces for sensitization (as verified by AFM) resulting in near unity yields for electron transfer from the molecular excited dyes into the conduction band.

  10. High-stringency screening of target-binding partners using a microfluidic device

    DOE Patents [OSTI]

    Soh, Hyongsok; Lou, Xinhui; Lagally, Eric

    2015-12-01

    The invention provides a method of screening a library of candidate agents by contacting the library with a target in a reaction mixture under a condition of high stringency, wherein the target includes a tag that responds to a controllable force applied to the tag, and passing the members of the library through a microfluidic device in a manner that exposes the library members to the controllable force, thereby displacing members of the library that are bound to the target relative to their unbound counterparts. Kits and systems for use with the methods of the invention are also provided.

  11. Matlab MEX-binding for SUNDIALS v2.1.1

    Energy Science and Technology Software Center (OSTI)

    2005-05-19

    sundialsTB is a Matlab interface to the SUNDIALS (Suite of Nonlinear, Algebraic/Differential equation Solvers).

  12. Secondary PDZ domain-binding site on class B plexins enhances...

    Office of Scientific and Technical Information (OSTI)

    Argonne, IL (US) Sponsoring Org: NIHOTHER Country of Publication: United States Language: ENGLISH Word Cloud More Like This Full Text Journal Articles DOI: 10.1073pnas.150893111

  13. Molecular mechanism of hydrocarbons binding to the metalorganic framework

    SciTech Connect (OSTI)

    Sun, Xiuquan; Wick, Collin D.; Thallapally, Praveen K.; McGrail, B. Peter; Dang, Liem X.

    2011-01-07

    The adsorption and diffusivity of methane, ethane, n-butane, n-hexane and cyclohexane in a metal organic framework (MOF) with the organic linker tetrakis[4-(carboxyphenyl)oxamethyl]methane, the metal salt, Zn2+, and organic pillar, 4,4-bipyridin was studied using molecular dynamics simulations. For the n-alkanes, the longer the chain, the lower the free energy of adsorption, which was attributed to a greater number of contacts between the alkane and MOF. Cyclohexane had a slightly higher adsorption free energy than n-hexane. Furthermore, for cyclo- and n-hexane, there were no significant differences in adsorption free energies between systems with low to moderate loadings. The diffusivity of the n-alkanes was found to strongly depend on chain length with slower diffusion for longer chains. Cyclohexane had no effective diffusion, suggesting that the selectivity the MOF has towards n-hexane over cyclohexane is the result of kinetics instead of energetics. This work was supported by the U.S. Department of Energy's (DOE) Office of Basic Energy Sciences, Chemical Sciences program. The Pacific Northwest National Laboratory is operated by Battelle for DOE.

  14. Study of lysozyme mobility and binding free energy during adsorption on a graphene surface

    SciTech Connect (OSTI)

    Nakano, C. Masato; Ma, Heng; Wei, Tao

    2015-04-13

    Understanding protein adsorption is a key to the development of biosensors and anti-biofouling materials. Hydration essentially controls the adsorption process on hydrophobic surfaces, but its effect is complicated by various factors. Here, we present an ideal model system to isolate hydration effects—lysozyme adsorption on a flat hydrophobic graphene surface. Our all-atom molecular dynamics and molecular-mechanics/Poisson-Boltzmann surface area computation study reveal that lysozyme on graphene displays much larger diffusivity than in bulk water. Protein's hydration free energy within the first hydration shell is dominated by the protein-water electrostatic interactions and acts as an energy barrier for protein adsorption. On the other hand, the surface tension, especially that from the hydrophobic graphene, can effectively weaken the barrier to promote adsorption.

  15. U-101: Mozilla Firefox / Thunderbird / SeaMonkey XBL Binding Use-After-Free Vulnerability

    Broader source: Energy.gov [DOE]

    A vulnerability has been reported in multiple Mozilla products, which can be exploited by malicious people to compromise a user's system.

  16. T-617: BIND RPZ Processing Flaw Lets Remote Users Deny Service

    Broader source: Energy.gov [DOE]

    When a name server is configured with a response policy zone (RPZ), queries for type RRSIG can trigger a server crash.

  17. Improving the Regeneration of CO?-Binding Organic Liquids with a Polarity Change

    SciTech Connect (OSTI)

    Mathias, Paul M.; Afshar, Kash; Zheng, Feng; Bearden, Mark D.; Freeman, Charles J.; Andrea, Tamer; Koech, Phillip K.; Kutnyakov, Igor V.; Zwoster, Andy; Smith, Arnold R.; Jessop, Philip G.; Nik, Omid Ghafari; Heldebrant, David J.

    2013-01-01

    This paper describes an unusual solvent regeneration method unique to CO?BOLs and other switchable ionic liquids; utilizing changes in polarity to shift the free energy of the system. The degree of CO? loading in CO?BOLs is known to control the polarity of the solvent; conversely, polarity could be exploited as a means to control CO? loading. In this process, a chemically inert non-polar antisolvent is added to aid in de-complexing CO? from a CO?-rich CO?BOL. The addition of this polarity assist reduces temperatures required for regeneration of CO?BOLs by as much as 76 C. The lower regeneration temperatures realized with this polarity change allow for reduced solvent attrition and thermal degradation. Furthermore, the polarity assist shows considerable promise for reducing regeneration energy of CO?BOL solvents, and separation of the CO?BOL from the antisolvent is as simple as cooling the mixture below the upper critical solution temperature. Vapour-liquid equilibrium and liquid-liquid equilibrium measurements of a candidate CO?BOL with CO? with and without an antisolvent were completed. From this data, we present the evidence and impacts of a polarity change on a CO?BOL. Thermodynamic models and analysis of the system were constructed using ASPEN Plus, and forecasts preliminary process configurations and feasibility are also presented. Lastly, projections of solvent performance for removing CO? from a sub-critical coal fired power plant (total net power and parasitic load) are presented with and without this polarity assist and compared to DOEs Case 10 MEA baseline.

  18. SC'14 HPC Dev. Workshop Session Presentation Template

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

    Xeon Phi(tm) Processor "Knights Landing" Architectural Overview Avinash Sodani, Senior Principal Engineer, Intel Corporation Chief Architect, Knights Landing Processor Copyright © 2015, Intel Corporation. All rights reserved Avinash Sodani ISC 2015 Intel® Xeon Phi (tm) Workshop. Next Intel® Xeon Phi(tm) Processor: Knights Landing First self-boot Xeon Phi(tm) processor that is binary compatible with main line IA Excellent scalar and vector performance Integration of Memory on

  19. Emergency Information Homepage | U.S. DOE Office of Science (SC)

    Office of Science (SC) Website

    Emergency Information Home Emergency Information Emergency Information Home Public Notifications Emergency Vocabulary Sheltering in Place Evacuation ISC Home Print Text Size: A A A FeedbackShare Page Oak Ridge conducts world-leading research that is advancing our nation's energy and national security portfolios. These activities are vital to securing America's future, but they can also pose potential risks. To help protect against possible incidents, the Emergency Management division works daily

  20. Emergency Vocabulary | U.S. DOE Office of Science (SC)

    Office of Science (SC) Website

    Emergency Vocabulary Emergency Information Emergency Information Home Public Notifications Emergency Vocabulary Sheltering in Place Evacuation ISC Home Emergency Vocabulary Print Text Size: A A A FeedbackShare Page In the event of an emergency on the Oak Ridge Reservation, you will hear one of the following terms during public announcements. Each term indicates the magnitude of the event and will help you understand any necessary protective actions. Operational Emergency: an event that does not

  1. Evacuation | U.S. DOE Office of Science (SC)

    Office of Science (SC) Website

    Evacuation Emergency Information Emergency Information Home Public Notifications Emergency Vocabulary Sheltering in Place Evacuation ISC Home Evacuation Print Text Size: A A A FeedbackShare Page Evacuations are ordered if a hazardous release could affect people in a specific area. If you are directed by local news or our website to evacuate your home or workplace please follow these guidelines: Write down the evacuation route and designated shelter provided by an EAS station. Instructions will

  2. Public Notifications | U.S. DOE Office of Science (SC)

    Office of Science (SC) Website

    Public Notifications Emergency Information Emergency Information Home Public Notifications Emergency Vocabulary Sheltering in Place Evacuation ISC Home Public Notifications Print Text Size: A A A FeedbackShare Page Warning sirens are placed around Oak Ridge's three major sites -- the Oak Ridge National Laboratory, Y-12 National Security Complex, and East Tennessee Technology Park. In the unlikely event of an off-site emergency, sirens will sound to alert area residents. If you hear the sirens,

  3. Sheltering in Place | U.S. DOE Office of Science (SC)

    Office of Science (SC) Website

    Sheltering in Place Emergency Information Emergency Information Home Public Notifications Emergency Vocabulary Sheltering in Place Evacuation ISC Home Sheltering in Place Print Text Size: A A A FeedbackShare Page If you are advised to shelter-in-place by local news or our website, please follow these instructions: Bring everyone inside (including pets). Close all doors and windows. Turn off and close all ventilation systems, including: Air conditioning Attic & exhaust fans Furnaces Fireplace

  4. Internal Short Circuit Device for Improved Lithium-Ion Battery Design -

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

    Energy Innovation Portal Vehicles and Fuels Vehicles and Fuels Energy Storage Energy Storage Find More Like This Return to Search Internal Short Circuit Device for Improved Lithium-Ion Battery Design National Renewable Energy Laboratory Contact NREL About This Technology Publications: PDF Document Publication NREL Internal Short Circuit (ISC) Fact Sheet (321 KB) Technology Marketing Summary Energy storage cells (also referred to herein as "cells" or "batteries") sold for

  5. NREL: Measurements and Characterization - Current Versus Voltage

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

    Current Versus Voltage The National Renewable Energy Laboratory (NREL) Device Performance group uses current versus voltage (I-V) measurement systems to assess the main performance parameters for photovoltaic (PV) cells and modules. I-V measurement systems determine the output performance of devices, including: open-circuit voltage (Voc), short-circuit current (Isc), fill factor (FF), maximum power output of the device (Pmax), voltage at maximum power (Vmax), current at maximum power (Imax), and

  6. Supplement Analysis

    Energy Savers [EERE]

    Supplement Analysis to the LCLS-ll Environmental Assessment, July. 2014 U.S. DEPARTMENT OF Office of *ENERGY 1 Science SLAG Site Office SLAC National Accelerator Laboratory 2575 Sand Hill Road, MS-8A Menlo Park, CA 94025 DATE: September 15, 2015 MEMORANDUM FOR: Paul Golan, Site Manager, SLAC Site Office THROUGH: James Elmore, ISC-OR NEPA Compliance Officer, Oak Ridge Office FROM: Mitzi Heard, NEPA Coornator, SLAC Site Office SUBJECT: Supplement Analysis to SLAC LCLS-I1 Environmental Assessment.

  7. Anion A HX Clusters with Reduced Electron Binding Energies: Proton vs Hydrogen Atom Relocation Upon Electron Detachment

    SciTech Connect (OSTI)

    Wang, Xue B.; Kass, Steven R.

    2014-12-10

    Clustering an anion with one or more neutral molecules is a stabilizing process that enhances the oxidation potential of the complex relative to the free ion. Several hydrogen bond clusters (i.e., A HX, where A = H2PO4 and CF3CO2 and HX = MeOH, PhOH, and Me2NOH or Et2NOH) are examined by photoelectron spectroscopy and M06-2X and CCSD(T) computations. Remarkably, these species are experimentally found to have adiabatic detachment energies that are smaller than those for the free ion and reductions of 0.47 to 1.87 eV are predicted computationally. Hydrogen atom and proton transfers upon vertical photodetachment are two limiting extremes on the neutral surface in a continuum of mechanistic pathways that account for these results, and the whole gamut of possibilities are predicted to occur.

  8. A Multi-Route Model of Nicotine-Cotinine Pharmacokinetics, Pharmacodynamics and Brain Nicotinic Acetylcholine Receptor Binding in Humans

    SciTech Connect (OSTI)

    Teeguarden, Justin G.; Housand, Conrad; Smith, Jordan N.; Hinderliter, Paul M.; Gunawan, Rudy; Timchalk, Charles

    2013-02-01

    The pharmacokinetics of nicotine, the pharmacologically active alkaloid in tobacco responsible for addiction, are well characterized in humans. We developed a physiologically based pharmacokinetic/pharmacodynamic model of nicotine pharmacokinetics, brain dosimetry and brain nicotinic acetylcholine receptor (nAChRs) occupancy. A Bayesian framework was applied to optimize model parameters against multiple human data sets. The resulting model was consistent with both calibration and test data sets, but in general underestimated variability. A pharmacodynamic model relating nicotine levels to increases in heart rate as a proxy for the pharmacological effects of nicotine accurately described the nicotine related changes in heart rate and the development and decay of tolerance to nicotine. The PBPK model was utilized to quantitatively capture the combined impact of variation in physiological and metabolic parameters, nicotine availability and smoking compensation on the change in number of cigarettes smoked and toxicant exposure in a population of 10,000 people presented with a reduced toxicant (50%), reduced nicotine (50%) cigarette Across the population, toxicant exposure is reduced in some but not all smokers. Reductions are not in proportion to reductions in toxicant yields, largely due to partial compensation in response to reduced nicotine yields. This framework can be used as a key element of a dosimetry-driven risk assessment strategy for cigarette smoke constituents.

  9. V-058: Microsoft Internet Explorer CDwnBindInfo Object Reuse Flaw Lets Remote Users Execute Arbitrary Code

    Broader source: Energy.gov [DOE]

    A vulnerability was reported in Microsoft Internet Explorer. A remote user can cause arbitrary code to be executed on the target user's system.

  10. T-633: BIND RRSIG RRsets Negative Caching Off-by-one Bug Lets Remote Users Deny Service

    Broader source: Energy.gov [DOE]

    A remote DNS server can supply very large RRSIG RRsets in a negative response to trigger an off-by-one error in a buffer size check and cause the target requesting named process to crash. A remote user can cause named to crash.

  11. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    Switch to Detail View for this search SciTech Connect Search Results Page 1 of 1 Search for: All records Creators/Authors contains: "CNR-ISC" × Sort by Relevance Sort by Date (newest first) Sort by Date (oldest first) Sort by Relevance « Prev Next » Everything7 Electronic Full Text0 Citations7 Multimedia0 Datasets0 Software0 Filter Results Filter by Subject temperature dependence (4) condensed matter physics, superconductivity and superfluidity (3) liquids (3) phase transformations

  12. Microsoft Word - S00416.doc

    Office of Legacy Management (LM)

    ;: A~1ENDED NOTICE OF RESIDUAL RADIOACTIVE CONTAMINATION T HIS NOTICE IS TO A L ERT B UYERS O R DE VELOPERS THAT RESIDU AL RAD IO A CT IVE CONTA MI NATIO N mrs O N THE P RO PERTY HERE IN DESC RI B ED . / EXISTS RECITALS A. WH EREAS , the current owner of the property known as the Salt Lake Vitro Site situated in the ~ county of Salt Lake , Salt Lake City , Utah . and more particularly described on Exhibit 1 attached herelol~'j,\ isC entral Valley Water Reclamation Facility Board located at 800

  13. Photoelectron imaging and theoretical study on the structure and chemical binding of the mixed-ligand M(I) complexes, [HMSH]{sup ?} (M = Cu, Ag, and Au)

    SciTech Connect (OSTI)

    Qin, Zhengbo; Liu, Zhiling; Cong, Ran; Xie, Hua; Tang, Zichao, E-mail: zctang@dicp.ac.cn, E-mail: fanhj@dicp.ac.cn; Fan, Hongjun, E-mail: zctang@dicp.ac.cn, E-mail: fanhj@dicp.ac.cn [State Key Laboratory of Molecular Reaction Dynamics, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023 (China)] [State Key Laboratory of Molecular Reaction Dynamics, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023 (China)

    2014-03-21

    We have reported a combined photoelectron imaging and theoretical study on gaseous mixed-ligand M(I) complexes of [HMSH]{sup ?} (M = Cu, Ag, and Au). With the aid of Franck-Condon simulations, vibrationally resolved photoelectron spectra yield accurate electron affinities of 3.269(6), 3.669(10), and 3.591(6) eV for [HCuSH], [HAgSH], and [HAuSH], respectively. And low-frequency modes are observed: 368(12) cm{sup ?1} for [HCuSH], 286(12) cm{sup ?1} for [HAgSH], and 327(12) cm{sup ?1} for [HAuSH], respectively. Extensive theoretical calculations are performed to aid in the spectral assignments and the calculated values agree well with the experimental observations. Although the S and H atoms have little discrepancy in electronegativity (2.20 for H and 2.54 for S), distinct bonding properties are demonstrated between HM and MS bond. It is revealed that there exists significant ionic bonding between MS in [HMSH]{sup ?} (M = Cu, Ag, and Au), while a gradual transition from ionic behavior between HCu in [HCuSH]{sup ?} to quite strong covalent bonding between HAu in [HAuSH]{sup ?}, supported by a variety of chemical bonding analyses.

  14. CO2-Binding Organic Liquids Gas Capture with Polarity-Swing-Assisted Regeneration Full Technology Feasibility Study B1 - Solvent-based Systems

    SciTech Connect (OSTI)

    Heldebrant, David J

    2014-08-31

    PNNL, Fluor Corporation and Queens University (Kingston, ON) successfully completed a three year comprehensive study of the CO2BOL water-lean solvent platform with Polarity Swing Assisted Regeneration (PSAR). This study encompassed solvent synthesis, characterization, environmental toxicology, physical, thermodynamic and kinetic property measurements, Aspen Plus™ modeling and bench-scale testing of a candidate CO2BOL solvent molecule. Key Program Findings The key program findings are summarized as follows: • PSAR favorably reduced stripper duties and reboiler temperatures with little/no impact to absorption column • >90% CO2 capture was achievable at reasonable liquid-gas ratios in the absorber • High rich solvent viscosities (up to 600 cP) were successfully demonstrated in the bench-scale system. However, the projected impacts of high viscosity to capital cost and operational limits compromised the other levelized cost of electricity benefits. • Low thermal conductivity of organics significantly increased the required cross exchanger surface area, and potentially other heat exchange surfaces. • CO2BOL had low evaporative losses during bench-scale testing • There was no evidence of foaming during bench scale testing • Current CO2BOL formulation costs project to be $35/kg • Ecotoxicity (Water Daphnia) was comparable between CO2BOL and MEA (169.47 versus 103.63 mg/L) • Full dehydration of the flue gas was determined to not be economically feasible. However, modest refrigeration (13 MW for the 550 MW reference system) was determined to be potentially economically feasible, and still produce a water-lean condition for the CO2BOLs (5 wt% steady-state water loading). • CO2BOLs testing with 5 wt% water loading did not compromise anhydrous performance behavior, and showed actual enhancement of CO2 capture performance. • Mass transfer of CO2BOLs was not greatly impeded by viscosity • Facile separation of antisolvent from lean CO2BOL was demonstrated on the bench cart • No measurable solvent degradation was observed over 4 months of testing – even with 5 wt% water present

  15. FlaF is a β-sandwich protein that anchors the archaellum in the archaeal cell envelope by binding the S-layer protein

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

    Banerjee, Ankan; Tsai, Chi -Lin; Chaudhury, Paushali; Tripp, Patrick; Arvai, Andrew  S.; Ishida, Justin  P.; Tainer, John  A.; Albers, Sonja -Verena

    2015-05-01

    Archaea employ the archaellum, a type IV pilus-like nanomachine, for swimming motility. In the crenarchaeon Sulfolobus acidocaldarius, the archaellum consists of seven proteins: FlaB/X/G/F/H/I/J. FlaF is conserved and essential for archaellum assembly but no FlaF structures exist. Here, we truncated the FlaF N terminus and solved 1.5-Å and 1.65-Å resolution crystal structures of this monotopic membrane protein. Structures revealed an N-terminal α-helix and an eight-strand β-sandwich, immunoglobulin-like fold with striking similarity to S-layer proteins. Crystal structures, X-ray scattering, and mutational analyses suggest dimer assembly is needed for in vivo function. The sole cell envelope component of S. acidocaldarius is amore » paracrystalline S-layer, and FlaF specifically bound to S-layer protein, suggesting that its interaction domain is located in the pseudoperiplasm with its N-terminal helix in the membrane. From these data, FlaF may act as the previously unknown archaellum stator protein that anchors the rotating archaellum to the archaeal cell envelope.« less

  16. High-Throughput Methodology for Discovery of Metal-Organic Frameworks with a High Binding Energy (New Joint UC-Berkeley/Symyx DoD/DLA Project) (presentation)

    Broader source: Energy.gov [DOE]

    Presented at the U.S. Department of Energy's Hydrogen Storage Meeting held June 26, 2007 in Bethesda, Maryland.

  17. Approaches to efficiently estimate solvation and explicit water energetics in ligand binding: the use of WaterMap [WaterMap and Its Implementation in Drug Discovery

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

    Yang, Yue; Wong, Sergio E.; Lightstone, Felice C.

    2012-09-08

    Solvents play quite an important role in most chemical and biological processes. It is widely accepted that the presence of water or other solvents in many chemical reactions can result in much lower energy barrier. In enzymatic catalysis, water mediated reaction pathways have been observed in various studies. In addition, different conformation flexibility and hydrogen bond patterns have been discovered for cyclic peptides in the presence of membrane and water, further illustrating the impact of solvent in biological activities such like membrane penetration. moreover, as will be discussed later in this review, water also plays a critical role in host-guestmore » chemistry and thus is essential to drug design. As such, it is not surprising that accounting for solvents is critical in drug discovery since drugs must modulate biological systems.« less

  18. FlaF is a ?-sandwich protein that anchors the archaellum in the archaeal cell envelope by binding the S-layer protein

    SciTech Connect (OSTI)

    Banerjee, Ankan; Tsai, Chi -Lin; Chaudhury, Paushali; Tripp, Patrick; Arvai, Andrew S.; Ishida, Justin P.; Tainer, John A.; Albers, Sonja -Verena

    2015-05-01

    Archaea employ the archaellum, a type IV pilus-like nanomachine, for swimming motility. In the crenarchaeon Sulfolobus acidocaldarius, the archaellum consists of seven proteins: FlaB/X/G/F/H/I/J. FlaF is conserved and essential for archaellum assembly but no FlaF structures exist. Here, we truncated the FlaF N terminus and solved 1.5- and 1.65- resolution crystal structures of this monotopic membrane protein. Structures revealed an N-terminal ?-helix and an eight-strand ?-sandwich, immunoglobulin-like fold with striking similarity to S-layer proteins. Crystal structures, X-ray scattering, and mutational analyses suggest dimer assembly is needed for in vivo function. The sole cell envelope component of S. acidocaldarius is a paracrystalline S-layer, and FlaF specifically bound to S-layer protein, suggesting that its interaction domain is located in the pseudoperiplasm with its N-terminal helix in the membrane. From these data, FlaF may act as the previously unknown archaellum stator protein that anchors the rotating archaellum to the archaeal cell envelope.

  19. NREL/NASA Internal Short-Circuit Instigator in Lithium Ion Cells; NREL (National Renewable Energy Laboratory)

    SciTech Connect (OSTI)

    Long, Dirk; Ireland, John; Pesaran, Ahmad; Darcy, Eric; Shoesmith, Mark; McCarthy, Ben

    2013-11-14

    NREL has developed a device to test one of the most challenging failure mechanisms of lithium-ion (Li-ion) batteries -- a battery internal short circuit. Many members of the technical community believe that this type of failure is caused by a latent flaw that results in a short circuit between electrodes during use. As electric car manufacturers turn to Li-ion batteries for energy storage, solving the short circuit problem becomes more important. To date, no reliable and practical method exists to create on-demand internal shorts in Li-ion cells that produce a response that is relevant to the ones produced by field failures. NREL and NASA have worked to establish an improved ISC cell-level test method that simulates an emergent internal short circuit, is capable of triggering the four types of cell internal shorts, and produces consistent and reproducible results. Internal short circuit device design is small, low-profile and implantable into Li-ion cells, preferably during assembly. The key component is an electrolyte-compatible phase change material (PCM). The ISC is triggered by heating the cell above PCM melting temperature (presently 40 degrees C 60 degrees C). In laboratory testing, the activated device can handle currents in excess of 300 A to simulate hard shorts (< 2 mohms). Phase change from non-conducting to conducting has been 100% successful during trigger tests.

  20. V, Ii. Pat-SC&~, Ciructor, Elvision of Techdcal Jkitiseru

    Office of Legacy Management (LM)

    V, Ii. Pat-SC&~, Ciructor, Elvision of Techdcal Jkitiseru I?. J. !%.Ltl2, Jr., chief, 5isC81bleDU3 Cperstions jw;ta, Prodcc' s.on Giviaion S-A-fiCi : PC: 3JS:?dl please '& advised that zrrangezkenta ?a-Je hem mde M.ti All.e~~ny ~~IWZI ta roll a% *Qdr %tcrylLct, 3. Y. plant on tkx3 firsC, xeclr4z.i of ZY&I m .nLh, %I=& shro*sgh June 1352, and -nil& !Sethlehe:a Stotl to roll at +,hai.r T~ckaxinna, 3. Y. plan% on the second n;ze:tznd of tk23 -IFx-xlth. 3: aould suaost, hcesvcr,

  1. Trajectory surface hopping study of the O({sup 3}P) + C{sub 2}H{sub 2} reaction dynamics: Effect of collision energy on the extent of intersystem crossing

    SciTech Connect (OSTI)

    Rajak, Karunamoy; Maiti, Biswajit

    2014-01-28

    Intersystem crossing (ISC) dynamics plays an important role in determining the product branching in the O({sup 3}P) + C{sub 2}H{sub 2} reaction despite the necessarily small spin-orbit coupling constant values. In this study we investigate the effect of collision energy on the extent of the contribution of a spin non-conserving route through ISC dynamics to the product distributions at the initial collision energies 8.2, 9.5, and 13.1 kcal/mol. A direct dynamics trajectory surface hopping method is employed with potential energy surfaces generated at the unrestricted B3LYP/6-31G(d,p) level of theory to perform nonadiabatic dynamics. To make our calculation simpler, nonadibatic transitions were only considered at the triplet-singlet intersections. At the crossing points, Landau-Zener transition probabilities were calculated using spin-orbit coupling constant values computed at the same geometry. The Landau-Zener model for the title reaction is validated against a more rigorous Tully's fewest switches method and found to be working reasonably well as expected because of weak spin-orbit coupling. We have compared our results with the recent crossed molecular beam experiments and observed a very good agreement with respect to the primary product branching ratios. Our calculation revealed that there is no noticeable effect of the initial collision energy on the overall product distributions that corroborates the recent experimental findings. Our calculation indicates, however, that the extent of intersystem crossing contributions varies significantly with collision energy, needed to be verified, experimentally.

  2. Calcium accumulated by sickle cell anemia red cells does not affect their potassium (86Rb+) flux components

    SciTech Connect (OSTI)

    Ortiz, O.E.; Lew, V.L.; Bookchin, R.M.

    1986-03-01

    We investigate here the hypothesis that the high Ca content of sickle cell anemia (SS) red cells may produce a sustained activation of the Ca2+-dependent K+ permeability (Gardos effect) and that the particularly high Ca levels in the dense SS cell fraction rich in irreversibly sickled cells (ISCs) might account for the Na pump inhibition observed in these cells. We measured active and passive 86Rb+ influx (as a marker for K+) in density-fractionated SS cells before and after extraction of their excess Ca by exposure to the Ca ionophore (A23187) and ethylene glycol tetra-acetic acid and with or without adenosine triphosphate depletion or addition of quinine. None of these maneuvers revealed any evidence of a Ca2+-dependent K leak in SS discocytes or dense cells. Na pump inhibition in the dense SS cells was associated with normal activation by external K+ and a low Vmax that persisted after Ca extraction from the cells. These results are consistent with our recent findings that the excess Ca in these cells is compartmentalized in intracellular inside-out vesicles and unavailable as free Ca2+ to the inner membrane surface. Although the steady-state free cytoplasmic Ca2+ in oxygenated SS cells must be below the levels needed to activate the K+ channel, possible brief activation of the channels of some SS cells resulting from transient elevations of cell Ca2+ during deoxygenation-induced sickling cannot be excluded. The dense, ISC-rich SS cell fraction showed a Ca2+-independent increase in the ouabain-resistant, nonsaturable component of 86Rb+ influx that, if uncompensated by Na+ gain, could contribute to the dehydration of these cells.

  3. Evaluation of Single Nucleotide Polymorphisms (SNPs) in the p53 Binding Protein 1 (TP53BP1) Gene in Breast Cancer Patients Treated With Breast-Conserving Surgery and Whole-Breast Irradiation (BCS + RT)

    SciTech Connect (OSTI)

    Haffty, Bruce G.; Goyal, Sharad; Kulkarni, Diptee; Green, Camille; Vazquez, Alexi; Schiff, Devora; Moran, Meena S.; Yang Qifeng; Ganesan, Shridar; Hirsfield, Kim M.

    2011-06-01

    Purpose: TP53BP1 is a key component of radiation-induced deoxyribonucleic acid damage repair. The purpose of this study was to evaluate the significance of a known common single nucleotide polymorphism in this gene (rs560191) in patients treated with breast-conserving surgery and whole-breast irradiation (BCS + RT). Methods and Materials: The population consisted of 176 premenopausal women treated with BCS + RT (median follow-up, 12 years). Genomic deoxyribonucleic acid was processed by use of TaqMan assays. Each allele for rs560191 was either C or G, so each patient was therefore classified as CC, CG, or GG. Patients were grouped as GG if they were homozygous for the variant G allele or CC-CG if they carried at least one copy of the common C allele (CC or CG). Results: Of the 176 women, 124 (71%) were CC-CG and 52 (29%) were GG. The mean age was 44 years for GG vs. 38 years for CC-CG (p < 0.001). GG was more common in African-American women than white women (69% vs. 13%, p < 0.001) and more commonly estrogen receptor negative (70% vs. 49%, p = 0.02). There were no significant correlations of rs560191 with other critical variables. Despite the fact that GG patients were older, the 10-year rate of local relapses was higher (22% for GG vs. 12% for CC-CG, p = 0.04). Conclusions: This novel avenue of investigation of polymorphisms in radiation repair/response genes in patients treated with BCS + RT suggests a correlation to local relapse. Additional evaluation is needed to assess the biological and functional significance of these single nucleotide polymorphisms, and larger confirmatory validation studies will be required to determine the clinical implications.

  4. Structure of a Putative Metal-Chelate Type ABC Transporter: An...

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

    nucleotide binding HI1470 subunits are in green and pink. The HI14701 transporter from Haemophilus influenzae belongs to the family of binding protein dependent bacterial ABC...

  5. An effective theory for the four-body system (Journal Article...

    Office of Scientific and Technical Information (OSTI)

    We compute the binding energies of the 4He tetramer and of alpha-particle. The ... Subject: 73 NUCLEAR PHYSICS AND RADIATION PHYSICS; ALPHA PARTICLES; BINDING ENERGY; ...

  6. Regulatory Interactions in ProKaryotes from RegTransBase () ...

    Office of Scientific and Technical Information (OSTI)

    of a protein (or RNA) directly binding to DNA or RNA mapping or prediction of binding ... Host Website: Lawrence Berkeley National Laboratory (LBNL) Sponsoring Org: USDOE Office of ...

  7. Experimental Investigation and High Resolution Simulation of In-Situ Combustion Processes

    SciTech Connect (OSTI)

    Margot Gerritsen; Tony Kovscek

    2008-04-30

    This final technical report describes work performed for the project 'Experimental Investigation and High Resolution Numerical Simulator of In-Situ Combustion Processes', DE-FC26-03NT15405. In summary, this work improved our understanding of in-situ combustion (ISC) process physics and oil recovery. This understanding was translated into improved conceptual models and a suite of software algorithms that extended predictive capabilities. We pursued experimental, theoretical, and numerical tasks during the performance period. The specific project objectives were (i) identification, experimentally, of chemical additives/injectants that improve combustion performance and delineation of the physics of improved performance, (ii) establishment of a benchmark one-dimensional, experimental data set for verification of in-situ combustion dynamics computed by simulators, (iii) develop improved numerical methods that can be used to describe in-situ combustion more accurately, and (iv) to lay the underpinnings of a highly efficient, 3D, in-situ combustion simulator using adaptive mesh refinement techniques and parallelization. We believe that project goals were met and exceeded as discussed.

  8. Q;ON-

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

    theBPA service standards and only then make a binding application for service. The second issue is if the binding notice must be no less than three years under all...

  9. Evaluation of Novel Design Strategies for Developing Zinc Finger Nucleases Tools for Treating Human Diseases

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

    Bach, Christian; Sherman, William; Pallis, Jani; Patra, Prabir; Bajwa, Hassan

    2014-01-01

    Zinc finger nucleases (ZFNs) are associated with cell death and apoptosis by binding at countless undesired locations. This cytotoxicity is associated with the binding ability of engineered zinc finger domains to bind dissimilar DNA sequences with high affinity. In general, binding preferences of transcription factors are associated with significant degenerated diversity and complexity which convolutes the design and engineering of precise DNA binding domains. Evolutionary success of natural zinc finger proteins, however, evinces that nature created specific evolutionary traits and strategies, such as modularity and rank-specific recognition to cope with binding complexity that are critical for creating clinical viable toolsmore » to precisely modify the human genome. Our findings indicate preservation of general modularity and significant alteration of the rank-specific binding preferences of the three-finger binding domain of transcription factor SP1 when exchanging amino acids in the 2nd finger.« less

  10. News Item

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

    Enhanced CO2 Capture in Metal-Organic Frameworks CO2 binding in BTT-type metal-organic framework: the highly porous MOF structure and, inset, detail of the CO2 binding site...

  11. Antibody Recognition of the Influenza Hemagglutinin by Receptor...

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

    to have neutralizing activity against divergent HA subtypes such as H3, H1, H2, and H5.2 The antibody binding site was mapped near the HA receptor binding site on the basis of...

  12. Identification and characterization of a bacterial hydrosulphide...

    Office of Scientific and Technical Information (OSTI)

    ... Country of Publication: United States Language: ENGLISH Subject: 08 HYDROGEN; BINDING ENERGY; BIOCHEMISTRY; BIOLOGY; BIOPHYSICS; CLOSTRIDIUM; CRYSTAL STRUCTURE; CYTOCHROME OXIDASE; ...

  13. DNA polymerase with modified processivity

    DOE Patents [OSTI]

    Bedford, Ella; Tabor, Stanley; Richardson, Charles C.

    1999-01-01

    Chimeric DNA polymerase having a DNA polymerase domain and processivity factor binding domain not naturally associated with DNA polymerase domain.

  14. Reoxidation of Bioreduced Uranium Under Reducing Conditions ...

    Office of Scientific and Technical Information (OSTI)

    Subject: 45 MILITARY TECHNOLOGY, WEAPONRY, AND NATIONAL DEFENSE; ACTINIDES; BINDING ENERGY; CALCIUM; CARBON; CARBONATES; ELECTRONS; GROUND WATER; MINING; NUCLEAR WEAPONS;...

  15. Drug development and manufacturing

    DOE Patents [OSTI]

    Warner, Benjamin P.; McCleskey, T. Mark; Burrell, Anthony K.

    2015-10-13

    X-ray fluorescence (XRF) spectrometry has been used for detecting binding events and measuring binding selectivities between chemicals and receptors. XRF may also be used for estimating the therapeutic index of a chemical, for estimating the binding selectivity of a chemical versus chemical analogs, for measuring post-translational modifications of proteins, and for drug manufacturing.

  16. Methods for production of proteins in host cells

    DOE Patents [OSTI]

    Donnelly, Mark; Joachimiak, Andrzej

    2004-01-13

    The present invention provides methods for the production of proteins, particularly toxic proteins, in host cells. The invention provides methods which use a fusion protein comprising a chaperonin binding domain in host cells induced or regulated to have increased levels of chaperonin which binds the chaperonin binding domain.

  17. Polypeptides having endoglucanase activity and polynucleotides encoding same

    DOE Patents [OSTI]

    Spodsberg, Nikolaj; Shagasi, Tarana

    2015-06-30

    The present invention relates to isolated polypeptides having endoglucanase activity, catalytic domains, cellulose binding domains and polynucleotides encoding the polypeptides, catalytic domains or cellulose binding domains. The invention also relates to nucleic acid constructs, vectors, and host cells comprising the polynucleotides as well as methods of producing and using the polypeptides, catalytic domains or cellulose binding domains.

  18. Annex D-200 Area Interim Storage Area Final Safety Analysis Report [FSAR] [Section 1 & 2

    SciTech Connect (OSTI)

    CARRELL, R D

    2002-07-16

    The 200 Area Interim Storage Area (200 Area ISA) at the Hanford Site provides for the interim storage of non-defense reactor spent nuclear fuel (SNF) housed in aboveground dry cask storage systems. The 200 Area ISA is a relatively simple facility consisting of a boundary fence with gates, perimeter lighting, and concrete and gravel pads on which to place the dry storage casks. The fence supports safeguards and security and establishes a radiation protection buffer zone. The 200 Area ISA is nominally 200,000 ft{sup 2} and is located west of the Canister Storage Building (CSB). Interim storage at the 200 Area ISA is intended for a period of up to 40 years until the materials are shipped off-site to a disposal facility. This Final Safety Analysis Report (FSAR) does not address removal from storage or shipment from the 200 Area ISA. Three different SNF types contained in three different dry cask storage systems are to be stored at the 200 Area ISA, as follows: (1) Fast Flux Test Facility Fuel--Fifty-three interim storage casks (ISC), each holding a core component container (CCC), will be used to store the Fast Flux Test Facility (FFTF) SNF currently in the 400 Area. (2) Neutron Radiography Facility (NRF) TRIGA'--One Rad-Vault' container will store two DOT-6M3 containers and six NRF TRIGA casks currently stored in the 400 Area. (3) Commercial Light Water Reactor Fuel--Six International Standards Organization (ISO) containers, each holding a NAC-I cask4 with an inner commercial light water reactor (LWR) canister, will be used for commercial LWR SNF from the 300 Area. An aboveground dry cask storage location is necessary for the spent fuel because the current storage facilities are being shut down and deactivated. The spent fuel is being transferred to interim storage because there is no permanent repository storage currently available.

  19. Characterization and dispersion of pollutant releases from the abrasive blasting of lead paint from steel bridges

    SciTech Connect (OSTI)

    Lee, M.; Rana, B.

    1999-07-01

    The characterization of airborne and spent material for abrasive blasting of steel paint was performed as part of the Environmental Impact Statement for Lead Paint Removal Operations on New York City Department of Transportation Bridges1. Laboratory tests were performed on painted steel components of the Williamsburg Bridge, to determine the sizes of particles typically released into the air as aerosol and onto the ground as bulk material, as a result of accidental releases from abrasive blasting operations. Two of the most commonly used abrasives for paint removal on steel structures, recyclable steel grit and expendable abrasives were subjected to the laboratory tests. The results of the tests were used to determine the percentage of existing paint and abrasive which becomes airborne and the resultant particle size distributions, which were employed in the air quality concentration and deposition modeling for the EIS. Particle size distributions of the airborne material indicated that the profiles of airborne lead and particulate matter have a mean particle size between 15 and 21 microns. Spent abrasives and paint chips that settle on the floor are larger in size with a mean diameter greater than 259 microns, although up to 6% of this material has a mean diameter less than 50 microns. The percentage of paint and expendable abrasives that become airborne as a result of abrasive blasting were estimated to be as high as 9.0 and 12.4%, respectively. Potential release rates were derived for total accumulation (duration of the project), annual, quarterly, 24-hour, and 1-hour time averaging periods for abrasives, lead, and other metals. Pollutant releases were simulated as individual sources at multiple release heights with the Environment Protection Agency's ISC3ST model for six representative bridges near potential places of public exposure.

  20. Neighborhood level health risk assessment of lead paint removal activities from elevated steel bridges

    SciTech Connect (OSTI)

    Conway, R.F.; Cohen, J.T.; Bowers, T.

    1999-07-01

    The New York City Department of Transportation (NYCDOT) has adopted strict containment and monitoring procedures during paint removal activities on its bridges because of the increasing awareness about lead poisoning in children in urban environments and the potential risk of lead-based paint releases during those activities. NYCDOT owns nearly 800 bridges scattered throughout New York City. Before undertaking paint removal activities as part of its ongoing preventive maintenance and rehabilitation program, NYCDOT recently conducted an analysis to determine the public health risk posed to children living near them. The analysis the first of its kind to assess the actual public health risk potential during both routine operations and upset conditions, or accidental releases evaluated the total and incremental blood lead levels from paint removal activities on more than 5,000 children from 6 months to 6 years old. Increases in baseline blood lead levels were estimated using several models, including EPA's Integrated Exposure Uptake Biokinetic (IEUBK) Model. This model estimates steady-state blood lead levels in children, reflecting exposure to lead in multiple media over an extended period of time. Increases in lead exposure from paint removal activities in the area surrounding the bridges was estimated using EPA's Industrial Source Complex (ISC3) model to calculate ambient air and deposition levels. Potential releases from the containment and ancillary equipment used in the paint removal process were modeled based on different release scenarios ranging from routine operations to complete failure of containment. To estimate the paint removal activities' contribution to long-term exterior dust lead levels (and its related interior component), a stochastic simulation model was developed for each block in the study area.

  1. Development of pollutant release estimates due to abrasive blasting for lead paint removal from New York City Department of Transportation steel bridges

    SciTech Connect (OSTI)

    Lee, M.; Domanski, J.

    1999-07-01

    The use of abrasive blasting techniques in the removal of lead paint from steel bridges is a subject of public health and environmental concerns. This process creates airborne dust that must be appropriately contained to prevent inhalation or ingestion exposure during the removal activity, since some of that dust contains lead and other metals. Lead particles, if not appropriately contained, can also settle in local soils or on and within buildings, and can ultimately be inhaled or ingested. Potential worst case release scenarios for the release of dust and pollutants from paint removal operations were developed as part of the analysis framework for the Environmental Impact Statement for Lead Paint Removal Operations on New York City Department of Transportation Bridges. A multi-step analytical framework was developed for the Environmental Impact Statement (EIS), aimed at characterizing and quantifying a series of worst case scenarios for the release of contaminated material into the environment. The pollutants that the analysis focused on were lead, respirable particulates (PM10), Total Suspended Particulates (TSP) and other metals. Samples of existing paint obtained from various surfaces of representative bridges were analyzed to determine average paint dry film thickness and the concentration of metals in the paint for each of the representative bridges. Samples of expendable abrasives were analyzed to determine the concentration of metals within the abrasives. Six scenarios were developed to encompass the range of potential releases that can occur during blasting operations. Two subcategories of hypothetical release events were developed for each scenario-- reasonable worst case events and maximum worst case events. Air quality dispersion modeling with the Environmental Protection Agency's ISC3ST model was employed with the predicted release rates.

  2. Highly Concentrated Palladium Hydrides/Deuterides; Theory

    SciTech Connect (OSTI)

    Papaconstantopoulos, Dimitrios

    2013-11-26

    Accomplishments are reported in these areas: tight-binding molecular dynamics study of palladium; First-principles calculations and tight-binding molecular dynamics simulations of the palladium-hydrogen system; tight-binding studies of bulk properties and hydrogen vacancies in KBH{sub 4}; tight-binding study of boron structures; development of angular dependent potentials for Pd-H; and density functional and tight-binding calculations for the light-hydrides NaAlH4 and NaBH4

  3. A proposal for positive cooperativity in anion-cation binding in yttrium and lutetium complexes based on o-amino-substituted phenolate ligands. On the way to coordination polymers by self-assembly. Molecular structures of [ClLu(OAr){sub 3}Na] (X-ray) and [ClY(OAr{prime}){sub 3}Y(OAr{prime}){sub 3}Na] (X-ray and {sup 89}Y-NMR)

    SciTech Connect (OSTI)

    Hogerheide, M.P.; Ringelberg, S.N.; Grove, D.M.

    1996-02-28

    The authors prepared the hetero(poly)metallic complexes [ClM(OAr){sub 3}Na] (M = Lu (3a), Y (3b)) and [ClY(OAr`){sub 3}Y(OAR`){sub 3}Na] (4) (OAr = OC{sub 6}H{sub 2}(CH{sub 2}NMe{sub 2}){sub 2}-2,6,Me-4; OAr` = OC{sub 6}H{sub 4}(CH{sub 2}NMe{sub 2})-2). Structural analysis was afforded by NMR spectroscopy and X-ray diffraction. The structures show evidence for anion-cation cooperativity in bonding and are discussed in detail for the compounds in both the solid state and in solution.

  4. Optical apparatus and method for sensing uranyl

    DOE Patents [OSTI]

    Baylor, L.C.; Buchanan, B.R.

    1994-01-01

    An optical sensing device for uranyl and other substances, a method for making an optical sensing device and a method for chemically binding uranyl and other indicators to glass, quartz, cellulose and similar substrates. The indicator, such as arsenazo III, is immobilized on the substrate using a chemical binding process. The immobilized arsenazo III causes uranyl from a fluid sample to bind irreversibly to the substrate at its active sites, thus causing absorption of a portion of light transmitted through the substrate. Determination of the amount of light absorbed, using conventional means, yields the concentration of uranyl present in the sample fluid. The binding of uranyl on the substrate can be reversed by subsequent exposure of the substrate to a solution of 2,6-pyridinedicarboxylic acid. The chemical binding process is suitable for similarly binding other indicators, such as bromocresol green.

  5. Fiber optic detector and method for using same for detecting chemical species

    DOE Patents [OSTI]

    Baylor, Lewis C. (North Augusta, SC); Buchanan, Bruce R. (Perkiomenville, PA)

    1995-01-01

    An optical sensing device for uranyl and other substances, a method for making an optical sensing device and a method for chemically binding uranyl and other indicators to glass, quartz, cellulose and similar substrates. The indicator, such as arsenazo III, is immobilized on the substrate using a chemical binding process. The immobilized arsenazo III causes uranyl from a fluid sample to bind irreversibly to the substrate at its active sites, thus causing absorption of a portion of light transmitted through the substrate. Determination of the amount of light absorbed, using conventional means, yields the concentration of uranyl present in the sample fluid. The binding of uranyl on the substrate can be reversed by subsequent exposure of the substrate to a solution of 2,6-pyridinedicarboxylic acid. The chemical binding process is suitable for similarly binding other indicators, such as bromocresol green.

  6. Stanford Synchrotron Radiation Lightsource

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

    The Long-sought Structure of α-Catenin Defines Its Functions for Cell-cell Interactions June 2013 SSRL Science Summary by Manuel Gnida, SLAC Office of Communications Figure Full-length α-catenin crystal structure reveals its dimeric asymmetric arrangement. The individual domains are colored individually (dimerization domain in yellow, vinculin binding domain in green, M-fragment in cyan, and the F-actin binding domain in magenta). A: View onto the vinculin binding domains. B: View onto the

  7. Computational study of Gleevec and G6G reveals molecular determinants of kinase inhibitor selectivity

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

    Lin, Yen -Lin; Meng, Yilin; Huang, Lei; Roux, Benoît

    2014-10-22

    Gleevec is a potent inhibitor of Abl tyrosine kinase but not of the highly homologous c-Src kinase. Because the ligand binds to an inactive form of the protein in which an Asp-Phe-Gly structural motif along the activation loop adopts a so-called DFG-out conformation, it was suggested that binding specificity was controlled by a “conformational selection” mechanism. In this context, the binding affinity displayed by the kinase inhibitor G6G poses an intriguing challenge. Although it possesses a chemical core very similar to that of Gleevec, G6G is a potent inhibitor of both Abl and c-Src kinases. Both inhibitors bind to themore » DFG-out conformation of the kinases, which seems to be in contradiction with the conformational selection mechanism. To address this issue and display the hidden thermodynamic contributions affecting the binding selectivity, molecular dynamics free energy simulations with explicit solvent molecules were carried out. Relative to Gleevec, G6G forms highly favorable van der Waals dispersive interactions upon binding to the kinases via its triazine functional group, which is considerably larger than the corresponding pyridine moiety in Gleevec. Upon binding of G6G to c-Src, these interactions offset the unfavorable free energy cost of the DFG-out conformation. When binding to Abl, however, G6G experiences an unfavorable free energy penalty due to steric clashes with the phosphate-binding loop, yielding an overall binding affinity that is similar to that of Gleevec. Such steric clashes are absent when G6G binds to c-Src, due to the extended conformation of the phosphate-binding loop.« less

  8. Microsoft Word - DOE-ID-15-061 Alabama EC B3-6.doc

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

    61 SECTION A. Project Title: Understanding the Interactions of Seawater Ions with Amidoxime through X-Ray Crystallography - The University of Alabama SECTION B. Project Description The University of Alabama (UA) proposes to understand how metal ions from seawater bind to uranium-selective amidoxime functionalized sorbents by experimentally determining the structures of metal complexes with molecules simulating the possible binding sites and characterizing these binding sites spectroscopically to

  9. Molecular Structure of the Brucella abortus Metalloprotein RicA, a

    Office of Scientific and Technical Information (OSTI)

    Rab2-Binding Virulence Effector (Journal Article) | SciTech Connect Molecular Structure of the Brucella abortus Metalloprotein RicA, a Rab2-Binding Virulence Effector Citation Details In-Document Search Title: Molecular Structure of the Brucella abortus Metalloprotein RicA, a Rab2-Binding Virulence Effector Authors: Herrou, Julien ; Crosson, Sean [1] + Show Author Affiliations UC Publication Date: 2014-10-02 OSTI Identifier: 1111169 Resource Type: Journal Article Resource Relation: Journal

  10. Analyses of Candida Cdc13 Orthologues Revealed a Novel OB Fold Dimer

    Office of Scientific and Technical Information (OSTI)

    Arrangement, Dimerization-Assisted DNA Binding, and Substantial Structural Differences between Cdc13 and RPA70 (Journal Article) | SciTech Connect Analyses of Candida Cdc13 Orthologues Revealed a Novel OB Fold Dimer Arrangement, Dimerization-Assisted DNA Binding, and Substantial Structural Differences between Cdc13 and RPA70 Citation Details In-Document Search Title: Analyses of Candida Cdc13 Orthologues Revealed a Novel OB Fold Dimer Arrangement, Dimerization-Assisted DNA Binding, and

  11. Structural basis for Tetrahymena telomerase processivity factor Teb1

    Office of Scientific and Technical Information (OSTI)

    binding to single-stranded telomeric-repeat DNA (Journal Article) | SciTech Connect SciTech Connect Search Results Journal Article: Structural basis for Tetrahymena telomerase processivity factor Teb1 binding to single-stranded telomeric-repeat DNA Citation Details In-Document Search Title: Structural basis for Tetrahymena telomerase processivity factor Teb1 binding to single-stranded telomeric-repeat DNA Authors: Zeng, Zhixiong ; Min, Bosun ; Huang, Jing ; Hong, Kyungah ; Yang, Yuting ;

  12. Attorney General's signed concurrence letter approved October 9, 2009 |

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

    Department of Energy Attorney General's signed concurrence letter approved October 9, 2009 Attorney General's signed concurrence letter approved October 9, 2009 Attorney General Consulation on binding Arbitration Guidance PDF icon AG Concurrence for BPA More Documents & Publications Letter from DOJ regarding Boneeville Power Administration's Guidance on the Use of Binding Arbitration for BPA Contracts Oct 2009 final concurrence letter for BPA BPA FINAL Binding Arbitration policy

  13. DNA Nanostructures as Models for Evaluating the Role of Enthalpy and

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

    Entropy in Polyvalent Binding Nanostructures as Models for Evaluating the Role of Enthalpy and Entropy in Polyvalent Binding Authors: Nangreave, J., Yan, H., and Liu, Y. Title: DNA Nanostructures as Models for Evaluating the Role of Enthalpy and Entropy in Polyvalent Binding Source: Journal of the American Chemical Society Year: 2011 Volume: 133 Pages: 4490-4497 ABSTRACT: DNA nanotechnology allows the design and construction of nanoscale objects that have finely tuned dimensions,

  14. Structures of P-glycoprotein reveal its conformational flexibility and an

    Office of Scientific and Technical Information (OSTI)

    epitope on the nucleotide-binding domain (Journal Article) | SciTech Connect SciTech Connect Search Results Journal Article: Structures of P-glycoprotein reveal its conformational flexibility and an epitope on the nucleotide-binding domain Citation Details In-Document Search Title: Structures of P-glycoprotein reveal its conformational flexibility and an epitope on the nucleotide-binding domain Authors: Ward, Andrew B. ; Szewczyk, Paul ; Grimard, Vinciane ; Lee, Chang-Wook ; Martinez, Lorena

  15. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    ... M2 receptor, offers possibilities for the design of mAChR subtype-selective ligands. ... Furthermore, molecular dynamics simulations suggest that tiotropium binds transiently to ...

  16. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    ... Multidomain Carbohydrate-binding Proteins Involved in Bacteroides thetaiotaomicron Starch Metabolism Cameron, Elizabeth A. ; Maynard, Mallory A. ; Smith, Christopher J. ; Smith, ...

  17. Nanolipoprotein particles and related compositions, methods and systems

    DOE Patents [OSTI]

    Hoeprich, Paul D; Fischer, Nicholas O; Mason, Peter W; Blanchette, Craig D

    2014-11-11

    Functionalized nanolipoprotein particle presenting an anchor substrate compound for binding with a corresponding anchor compound presented on a target molecule, and related compositions methods and systems.

  18. Expression of eukaryotic polypeptides in chloroplasts

    DOE Patents [OSTI]

    Mayfield, Stephen P.

    2013-06-04

    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.

  19. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    Filter Results Filter by Subject membranes (2) architecture (1) binding energy (1) biochemistry (1) biology (1) biophysics (1) clostridium (1) crystal structure (1) cytochrome ...

  20. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    ... Filter Results Filter by Subject applied life sciences (1) basic biological sciences (1) binding energy (1) biochemistry (1) biology (1) biophysics (1) chromatin (1) clostridium ...

  1. SSRL HEADLINES July 2003

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

    Synthase Complementing Protein as a Novel Antibacterial Drug Target (contacts: Irimpan Mathews; Ashley Deacon) SSRL scientists have determined key binding sites in an enzyme family...

  2. Jeffrey Long | Center for Gas SeparationsRelevant to Clean Energy...

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

    Research Within the CGS, the Long group is synthesizing and characterizing new metal-organic frameworks (MOFs) with functionalized surfaces that enable selective binding of one...

  3. Protein Flips Lipids Across Membranes

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

    Protein Flips Lipids Across Membranes Print Found ubiquitously in both bacteria and humans, membrane proteins of the adenosine triphosphate (ATP)-binding cassette (ABC) transporter...

  4. Comments to NAESB Long Term Competition (Rollover Rights) Business...

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

    However, BPA disagrees with the prescriptive nature of the standards which obligate the TSP to bind the challenger at the very beginning of the competition process. BPA is...

  5. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    ... States) Inhalation Toxicology Research Institute ... February 2015 Emission mechanisms in Al-rich AlGaNAlN ... were calculated by two methods, a tight-binding method ...

  6. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    Covalent agonists for studying G protein-coupled receptor activation Weichert, Dietmar ; ... X-ray crystallographic analysis of adipocyte fatty acid binding protein (aP2) modified ...

  7. Directory

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

    NEUP Final Report 11-3049 NEUP Final Report 11-3049 Selectivity in Ligand Binding to Uranyl Compounds: A Synthetic, Structural, Thermodynamic and Comput... (Properties) 52915...

  8. Becoming a Customer

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

    parts of the OATT and Transmission Services Business Practices to best understand the terms and conditions of open access transmission service that determine the binding rights...

  9. Tax Credits, Rebates & Savings | Department of Energy

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

    Photovoltaics Solar Easements Ohio's solar-easement provisions are similar to those in effect in other states. Ohio law allows property owners to create binding solar easements...

  10. Structure and Receptor Specificity of an Avian Flu Antigen

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

    combined effects could allow the Viet04 virus to escape entrapment by mucins in the lungs and increase binding to susceptible human epithelial cells. These mutations therefore...

  11. LANL: AOT & LANSCE The Pulse June 2010

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

    protein, which enables humans to breathe. Hb efficiently transports oxygen (O 2 ) from lungs to tissues. Hb's ability to function properly depends tremendously on binding hydrogen...

  12. High-Order Membrane Complexes from Activated G-Protein Subunits

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

    processes initiated in response to external (extracellular) signals such as hormones, neurotransmitters, or light are regulated by a complex dance involving GTP-binding...

  13. Eta-mesic nuclei: Past, present, future Haider, Q. [Fordham Univ...

    Office of Scientific and Technical Information (OSTI)

    Liu, Lon -Chang Los Alamos National Lab. (LANL), Los Alamos, NM (United States) 73 NUCLEAR PHYSICS AND RADIATION PHYSICS Eta-mesic nuclei; final-state interaction; binding...

  14. TITLE AUTHORS SUBJECT SUBJECT RELATED DESCRIPTION PUBLISHER AVAILABILI...

    Office of Scientific and Technical Information (OSTI)

    NY United States Liu Lon Chang Los Alamos National Lab LANL Los Alamos NM United States NUCLEAR PHYSICS AND RADIATION PHYSICS Eta mesic nuclei final state interaction binding...

  15. Renewable Energy Rights

    Broader source: Energy.gov [DOE]

    Vermont law forbids ordinances, bylaws, deed restrictions, covenants, declarations, or similar binding agreements from prohibiting (or having the effect of prohibiting) the use of solar collectors,...

  16. How 3D Printers Work | Department of Energy

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

    blueprint is created, the printer needs to be prepared. This includes refilling the raw materials (such as plastics, metal powders or binding solutions) and preparing the build...

  17. Cubic nitride templates (Patent) | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    The process includes solutions of one or more metal precursor and soluble polymers having binding properties for the one or more metal precursor. After a coating operation, the ...

  18. Beneficial Use of Carbon Dioxide in Precast Concrete Production...

    Office of Scientific and Technical Information (OSTI)

    in binding matrix. Two typical precast products are examined for their capacity to store carbon dioxide during the production. They are concrete blocks and fiber-cement panels. ...

  19. PYGridWare wsdl2python: python client stub generator

    Energy Science and Technology Software Center (OSTI)

    2003-08-01

    PyGridWare wsdl2python stub generator is used to automatically generate Python bindings to a Web Service given a Web Service Description Language (WSDL) file.

  20. SSRL HEADLINES May 2007

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

    structure of an ATP-binding Cassette (ABC) transporter called HI14701 from the bacteria Haemophilus influenzae. This particular transporter, which is a member of a large family...

  1. ALSNews Vol. 368

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

    Binding Behavior of Dopamine Transporter Key to Understanding Chemical Reactions in the Brain Scientists working at the ALS recently solved the crystallographic structures of...

  2. OSTIblog Posts by Moderator | OSTI, US Dept of Energy, Office of Scientific

    Office of Scientific and Technical Information (OSTI)

    and Technical Information Moderator Moderator's picture Ideas That Bind Published on Sep 10, 2009 by David Kaiser (MIT) and Luis Bettencourt (LANL)

  3. Nuclear localization of the DNA repair scaffold XRCC1: Uncovering the functional role of a bipartite NLS

    SciTech Connect (OSTI)

    Kirby, Thomas W.; Gassman, Natalie R.; Smith, Cassandra E.; Pedersen, Lars C.; Gabel, Scott A.; Sobhany, Mack; Wilson, Samuel H.; London, Robert E.

    2015-08-25

    We have characterized the nuclear localization signal (NLS) of XRCC1 structurally using X-ray crystallography and functionally using fluorescence imaging. Crystallography and binding studies confirm the bipartite nature of the XRCC1 NLS interaction with Importin α (Impα) in which the major and minor binding motifs are separated by >20 residues, and resolve previous inconsistent determinations. Binding studies of peptides corresponding to the bipartite NLS, as well as its major and minor binding motifs, to both wild-type and mutated forms of Impα reveal pronounced cooperative binding behavior that is generated by the proximity effect of the tethered major and minor motifs of the NLS. The cooperativity stems from the increased local concentration of the second motif near its cognate binding site that is a consequence of the stepwise binding behavior of the bipartite NLS. We predict that the stepwise dissociation of the NLS from Impα facilitates unloading by providing a partially complexed intermediate that is available for competitive binding by Nup50 or the Importin β binding domain. This behavior gives a basis for meeting the intrinsically conflicting high affinity and high flux requirements of an efficient nuclear transport system.

  4. News Item

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

    the interaction of nanoparticles with cells. We have investigated how proteins found in blood serum affect the cellular binding of protein-nanoparticle complexes. Using...

  5. Electronic and spin transport properties of graphene nanoribbon...

    Office of Scientific and Technical Information (OSTI)

    (QUAMBOs), a first-principles tight binding (TB) scheme based on density functional theory (DFT), combined with a non-equilibrium Green's function. For electronic transport,...

  6. Ancient Proteins Help Unravel a Modern Cancer Drug's Mechanism

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

    Print The cancer drug Gleevec is extremely specific, binding and inhibiting only the cancer-causing tyrosine protein kinase Blc-Abl, while not targeting homologous protein...

  7. Gas sensor incorporating a porous framework

    DOE Patents [OSTI]

    Yaghi, Omar M.; Czaja, Alexander U.; Wang, Bo; Furukawa, Hiroyasu; Galatsis, Kosmas; Wang, Kang L.

    2013-07-09

    The disclosure provides sensor for gas sensing including CO.sub.2 gas sensors comprising a porous framework sensing area for binding an analyte gas.

  8. ALSNews Vol. 365

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

    Gleevec is extremely specific, binding and inhibiting only the cancer-causing tyrosine protein kinase Blc-Abl, while not targeting homologous protein kinases found in normal,...

  9. SLAC-PUB-8640

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

    those solutions represented, it was not the proton. Heisenberg suggested that a new force was needed to explain the binding of protons inside the nucleus. Stern's measurement...

  10. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    ... Surface and molecular analogues display similar properties, in terms of DEAS binding constants absorption maxima and luminescence properties (intense emission band assigned to a ...

  11. NEAR-IR TWO PHOTON MICROSCOPY IMAGING OF SILICA NANOPARTICLES...

    Office of Scientific and Technical Information (OSTI)

    Surface and molecular analogues display similar properties, in terms of DEAS binding constants absorption maxima and luminescence properties (intense emission band assigned to a ...

  12. ALS Capabilities Reveal How Like Can Attract Like

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

    by water-binding energy, as predicted by theory. The chemical information that one can extract from such experimental data alone is limited, so researchers interpreted the spectra...

  13. T-572: VMware ESX/ESXi SLPD denial of service vulnerability

    Broader source: Energy.gov [DOE]

    VMware ESX/ESXi SLPD denial of service vulnerability and ESX third party updates for Service Console packages bind, pam, and rpm.

  14. Anomalous liquid scintillation counting of chromium-51

    SciTech Connect (OSTI)

    Charig, A.; Blake-Haskins, J.; Eigen, E.

    1985-12-01

    Unusual behavior of chromium-51 in liquid scintillation cocktail is described. Rapidly declining count rate is attributed to first-order binding of chromate to glass vials.

  15. Molecular Structure of the Brucella abortus Metalloprotein RicA...

    Office of Scientific and Technical Information (OSTI)

    Journal Article: Molecular Structure of the Brucella abortus Metalloprotein RicA, a Rab2-Binding Virulence Effector Citation Details In-Document Search Title: Molecular Structure ...

  16. Ancient Proteins Help Unravel a Modern Cancer Drug's Mechanism

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

    Ancient Proteins Help Unravel a Modern Cancer Drug's Mechanism Print The cancer drug Gleevec is extremely specific, binding and inhibiting only the cancer-causing tyrosine protein...

  17. Nuclear localization of the DNA repair scaffold XRCC1: Uncovering the functional role of a bipartite NLS

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

    Kirby, Thomas W.; Gassman, Natalie R.; Smith, Cassandra E.; Pedersen, Lars C.; Gabel, Scott A.; Sobhany, Mack; Wilson, Samuel H.; London, Robert E.

    2015-08-25

    We have characterized the nuclear localization signal (NLS) of XRCC1 structurally using X-ray crystallography and functionally using fluorescence imaging. Crystallography and binding studies confirm the bipartite nature of the XRCC1 NLS interaction with Importin α (Impα) in which the major and minor binding motifs are separated by >20 residues, and resolve previous inconsistent determinations. Binding studies of peptides corresponding to the bipartite NLS, as well as its major and minor binding motifs, to both wild-type and mutated forms of Impα reveal pronounced cooperative binding behavior that is generated by the proximity effect of the tethered major and minor motifs ofmore » the NLS. The cooperativity stems from the increased local concentration of the second motif near its cognate binding site that is a consequence of the stepwise binding behavior of the bipartite NLS. We predict that the stepwise dissociation of the NLS from Impα facilitates unloading by providing a partially complexed intermediate that is available for competitive binding by Nup50 or the Importin β binding domain. This behavior gives a basis for meeting the intrinsically conflicting high affinity and high flux requirements of an efficient nuclear transport system.« less

  18. Toward Design of a Universal Flu Vaccine

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

    large structural differences from CR9114, indicating that, while they bind to a similar region on various viruses, they employ different strategies for neutralizing those...

  19. SO2907, A Putative TonB-dependent Receptor, Is Involved in Dissimilato...

    Office of Scientific and Technical Information (OSTI)

    Iron binding assays using isothermal titration calorimetry and fluorescence tryptophan ... RESPIRATION; STRAINS; TITRATION; TRYPTOPHAN; VALENCE Word Cloud More Like This Full ...

  20. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    ... Previous bioinformatics analysis revealed a putative oligonucleotideoligosaccharide-binding (OB) fold at the N terminus of Stn1 (Stn1N) that shows limited sequence similarity to ...