Sample records for isc bind deleted

  1. 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.

  2. DsrR, a Novel IscA-like Protein Lacking Iron- and Fe-S-Binding...

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

    scaffolds. However, DsrR does not retain the Fe-S- or the iron-binding ability of these proteins, which is due to the lack of all three highly conserved cysteine residues of...

  3. IXPUG ISC Documents

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

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

  4. IXPUG ISC Documents

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

    AFDC Printable Version Share this resource Send a link to EERE: Alternative Fuels Data Center Home Page to someone by E-mail Share EERE: Alternative Fuels Data Center Home Page on Facebook Tweet about EERE: Alternative Fuels Data Center Home Page on Twitter Bookmark EERE: Alternative1 First Use of Energy for All Purposes (Fuel and Nonfuel), 2002; Level: National5Sales for4,645U.S. DOEThe Bonneville PowerCherries 82981-1cnHigh School footballHydrogenIT | National NuclearIWTUBoF: IXPUG ISC15 BoF

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

    E-Print Network [OSTI]

    Sancho, Javier

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

  6. CCAAT/enhancer binding protein {beta} deletion increases mitochondrial function and protects mice from LXR-induced hepatic steatosis

    SciTech Connect (OSTI)

    Rahman, Shaikh M., E-mail: rmizanoor@hotmail.com [Department of Pediatrics, School of Medicine, University of Colorado Denver, Aurora, CO 80045 (United States); Choudhury, Mahua; Janssen, Rachel C.; Baquero, Karalee C. [Department of Pediatrics, School of Medicine, University of Colorado Denver, Aurora, CO 80045 (United States)] [Department of Pediatrics, School of Medicine, University of Colorado Denver, Aurora, CO 80045 (United States); Miyazaki, Makoto [Division of Renal Diseases and Hypertension, School of Medicine, University of Colorado Denver, Aurora, CO 80045 (United States)] [Division of Renal Diseases and Hypertension, School of Medicine, University of Colorado Denver, Aurora, CO 80045 (United States); Friedman, Jacob E. [Department of Pediatrics, School of Medicine, University of Colorado Denver, Aurora, CO 80045 (United States) [Department of Pediatrics, School of Medicine, University of Colorado Denver, Aurora, CO 80045 (United States); Department of Biochemistry and Molecular Genetics, School of Medicine, University of Colorado Denver, Aurora, CO 80045 (United States)

    2013-01-04T23:59:59.000Z

    Highlights: Black-Right-Pointing-Pointer LXR agonist activation increases liver TG accumulation by increasing lipogenesis. Black-Right-Pointing-Pointer C/EBP{beta}{sup -/-} mouse prevents LXR activation-mediated induction of hepatic lipogenesis. Black-Right-Pointing-Pointer C/EBP{beta} deletion increases mitochondrial transport chain function. Black-Right-Pointing-Pointer Beneficial effects of LXR activation on liver cholesterol metabolism did not change. Black-Right-Pointing-Pointer C/EBP{beta} inhibition might have important therapeutic potential. -- Abstract: Drugs designed specifically to activate liver X receptors (LXRs) have beneficial effects on lowering cholesterol metabolism and inflammation but unfortunately lead to severe hepatic steatosis. The transcription factor CCAAT/enhancer binding protein beta (C/EBP{beta}) is an important regulator of liver gene expression but little is known about its involvement in LXR-based steatosis and cholesterol metabolism. The present study investigated the role of C/EBP{beta} expression in LXR agonist (T0901317)-mediated alteration of hepatic triglyceride (TG) and lipogenesis in mice. C/EBP{beta} deletion in mice prevented LXR agonist-mediated induction of lipogenic gene expression in liver in conjunction with significant reduction of liver TG accumulation. Surprisingly, C/EBP{beta}{sup -/-} mice showed a major increase in liver mitochondrial electron chain function compared to WT mice. Furthermore, LXR activation in C/EBP{beta}{sup -/-} mice increased the expression of liver ATP-binding cassette transporter ABCG1, a gene implicated in cholesterol efflux and reducing blood levels of total and LDL-cholesterol. Together, these findings establish a central role for C/EBP{beta} in the LXR-mediated steatosis and mitochondrial function, without impairing the influence of LXR activation on lowering LDL and increasing HDL-cholesterol. Inactivation of C/EBP{beta} might therefore be an important therapeutic strategy to prevent LXR activation-mediated adverse effects on liver TG metabolism without disrupting its beneficial effects on cholesterol metabolism.

  7. Interim storage cask (ISC), a concrete and steel dry storage cask

    SciTech Connect (OSTI)

    Grenier, R.M.; Koploy, M.A. [General Atomics, San Diego, CA (United States)

    1995-12-31T23:59:59.000Z

    General Atomics (GA) has designed and is currently fabricating the Interim Storage Cask (ISC) for Westinghouse Hanford Company (WHC). The ISC is a dry storage cask that will safely store a Core Component Container (CCC) with Fast Flux Test Facility (FFTF) spent fuel assemblies or fuel pin containers for a period of up to 50 years at the US Department of Energy (DOE) Hanford site. The cask may also be used to transfer the fuel to different areas within the Hanford site. The ISC is designed to stringent criteria from both 10CFR71 and 10CFR72 for safe storage and on-site transportation of FFTF spent fuel and fuel pin containers. The cask design uses a combination of steel and concrete materials to achieve a cost-effective means of storing spent fuel. The casks will be extensively tested before use to verify that the design and construction meet the design requirements.

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

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

    the target resolver to crash IMPACT: Triggering this defect will cause the affected server to exit with an error, denying service to recursive DNS clients that use that...

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

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

    AFDC Printable Version Share this resource Send a link to EERE: Alternative Fuels Data Center Home Page to someone by E-mail Share EERE: Alternative Fuels Data Center Home Page on Facebook Tweet about EERE: Alternative Fuels Data Center Home Page on Twitter Bookmark EERE: Alternative1 First Use of Energy for All Purposes (Fuel and Nonfuel), 2002; Level: National5Sales for4,645 3,625 1,006 492 742EnergyOn April 23, 2014,Zaleski -BlueprintThisVulnerabilities |Vulnerability |PROBLEM:|Department

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

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

    AFDC Printable Version Share this resource Send a link to EERE: Alternative Fuels Data Center Home Page to someone by E-mail Share EERE: Alternative Fuels Data Center Home Page on Facebook Tweet about EERE: Alternative Fuels Data Center Home Page on Twitter Bookmark EERE: Alternative1 First Use of Energy for All Purposes (Fuel and Nonfuel), 2002; Level: National5Sales for4,645 3,625 1,006 492 742EnergyOn April 23,EnergyChicopeeTechnologyfactTuscarora Phase IIDOE OGain Unauthorizedquery.c |

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

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

    AFDC Printable Version Share this resource Send a link to EERE: Alternative Fuels Data Center Home Page to someone by E-mail Share EERE: Alternative Fuels Data Center Home Page on Facebook Tweet about EERE: Alternative Fuels Data Center Home Page on Twitter Bookmark EERE: Alternative1 First Use of Energy for All Purposes (Fuel and Nonfuel), 2002; Level: National5Sales for4,645 3,625 1,006 492 742Energy China 2015of 2005UNSDepartmentFebruaryPhase|PotomacDepartment ofConduct

  12. Improving the fidelity of deletion

    SciTech Connect (OSTI)

    Adhikari, Satyabrata; Choudhury, B. S. [Department of Mathematics, Bengal Engineering and Science University, Howrah-711103, West Bengal (India)

    2006-05-15T23:59:59.000Z

    In this work we study the quantum deletion machine with two transformers, and show that the deletion machine with a single transformer performs better than the deletion machine with more than two transformers. We also observe that the fidelity of deletion depends on the blank state used in the deleter, and so for different blank states the fidelity is different. Further, we study the Pati-Braunsein deleter with transformer.

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

    Office of Science (SC) Website

    AFDC Printable Version Share this resource Send a link to EERE: Alternative Fuels Data Center Home Page to someone by E-mail Share EERE: Alternative Fuels Data Center Home Page on Facebook Tweet about EERE: Alternative Fuels Data Center Home Page on Twitter Bookmark EERE: Alternative1 First Use of Energy for All Purposes (Fuel and Nonfuel), 2002; Level:Energy: Grid Integration Redefining What'sis Taking Over OurThe Iron4 Self-Scrubbing:,,ofOpportunitieshighlights/ The Office» HowHumanISC

  14. REVIEW OF FAST FLUX TEST FACILITY (FFTF) FUEL EXPERIMENTS FOR STORAGE IN INTERIM STORAGE CASKS (ISC)

    SciTech Connect (OSTI)

    CHASTAIN, S.A.

    2005-10-24T23:59:59.000Z

    Appendix H, Section H.3.3.10.11 of the Final Safety Analysis Report (FSAR), provides the limits to be observed for fueled components authorized for storage in the Fast Flux Test Facility (FFTF) spent fuel storage system. Currently, the authorization basis allows standard driver fuel assemblies (DFA), as described in the FSAR Chapter 17, Section 17.5.3.1, to be stored provided decay power per assembly is {le} 250 watts, post-irradiation time is four years minimum, average assembly burn-up is 150,000 MWD/MTHM maximum and the pre-irradiation enrichment is 29.3% maximum (per H.3.3.10.11). In addition, driver evaluation (DE), core characterizer assemblies (CCA), and run-to-cladding-breach (RTCB) assemblies are included based on their similarities to a standard DFA. Ident-69 pin containers with fuel pins from these DFAs can also be stored. Section H.3.3.10.11 states that fuel types outside the specification criteria above will be addressed on a case-by-case basis. There are many different types of fuel and blanket experiments that were irradiated in the FFTF which now require offload to the spent fuel storage system. Two reviews were completed for a portion of these special type fuel components to determine if placement into the Core Component Container (CCC)/Interim Storage Cask (ISC) would require any special considerations or changes to the authorization basis. Project mission priorities coupled with availability of resources and analysts prevented these evaluations from being completed as a single effort. Areas of review have included radiological accident release consequences, radiological shielding adequacy, criticality safety, thermal limits, confinement, and stress. The results of these reviews are available in WHC-SD-FF-RPT-005, Rev. 0 and 1, ''Review of FFTF Fuel Experiments for Storage at ISA'', (Reference I), which subsequently allowed a large portion of these components to be included in the authorization basis (Table H.3.3-21). The report also identified additional components and actions in Section 3.0 and Table 3 that require further evaluation. The purpose of this report is to evaluate another portion of the remaining inventory (i.e., delayed neutron signal fuel, blanket assemblies, highly enriched assemblies, newly loaded Ident-69 pin containers, and returned fuel) to ensure it can be safely off loaded to the FFTF spent fuel storage system.

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

    E-Print Network [OSTI]

    Iglesia, Enrique

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

  16. Stabilizing the cystic fibrosis transmembrane conductance regulator (CFTR) by nucleotide derivative binding to promote proper folding

    E-Print Network [OSTI]

    Smith, Ryan Craig

    2013-02-22T23:59:59.000Z

    Seventy percent of people who suffer from cystic fibrosis have a cystic fibrosis transmembrane conductance regulator gene on chromosome 7 that contains a three base-pair deletion of phenylalanine at position 508, in a nucleotide binding domain...

  17. IXPUG ISC Documents

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

    AFDC Printable Version Share this resource Send a link to EERE: Alternative Fuels Data Center Home Page to someone by E-mail Share EERE: Alternative Fuels Data Center Home Page on Facebook Tweet about EERE: Alternative Fuels Data Center Home Page on Twitter Bookmark EERE: Alternative1 First Use of Energy for All Purposes (Fuel and Nonfuel), 2002; Level: National5Sales for4,645U.S. DOE Office of Science (SC) EnvironmentalGyroSolé(tm)Hydrogen StorageITERITER Subscribe to RSS - ITER ITER

  18. IXPUG ISC Documents

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

    AFDC Printable Version Share this resource Send a link to EERE: Alternative Fuels Data Center Home Page to someone by E-mail Share EERE: Alternative Fuels Data Center Home Page on Facebook Tweet about EERE: Alternative Fuels Data Center Home Page on Twitter Bookmark EERE: Alternative1 First Use of Energy for All Purposes (Fuel and Nonfuel), 2002; Level: National5Sales for4,645U.S. DOEThe Bonneville PowerCherries 82981-1cnHigh School footballHydrogenIT | National NuclearIWTU Construction

  19. IXPUG ISC Documents

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

    AFDC Printable Version Share this resource Send a link to EERE: Alternative Fuels Data Center Home Page to someone by E-mail Share EERE: Alternative Fuels Data Center Home Page on Facebook Tweet about EERE: Alternative Fuels Data Center Home Page on Twitter Bookmark EERE: Alternative1 First Use of Energy for All Purposes (Fuel and Nonfuel), 2002; Level: National5Sales for4,645U.S. DOEThe Bonneville PowerCherries 82981-1cnHigh School footballHydrogenIT | National NuclearIWTU ConstructionBoF:

  20. IXPUG ISC Documents

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

    AFDC Printable Version Share this resource Send a link to EERE: Alternative Fuels Data Center Home Page to someone by E-mail Share EERE: Alternative Fuels Data Center Home Page on Facebook Tweet about EERE: Alternative Fuels Data Center Home Page on Twitter Bookmark EERE: Alternative1 First Use of Energy for All Purposes (Fuel and Nonfuel), 2002; Level: National5Sales for4,645U.S. DOEThe Bonneville PowerCherries 82981-1cnHigh School footballHydrogenIT | National NuclearIWTU

  1. Method for introducing unidirectional nested deletions

    DOE Patents [OSTI]

    Dunn, John J. (Bellport, NY); Quesada, Mark A. (Horseheads, NY); Randesi, Matthew (New York, NY)

    2001-01-01T23:59:59.000Z

    Disclosed is a method for the introduction of unidirectional deletions in a cloned DNA segment in the context of a cloning vector which contains an f1 endonuclease recognition sequence adjacent to the insertion site of the DNA segment. Also disclosed is a method for producing single-stranded DNA probes utilizing the same cloning vector. An optimal vector, PZIP is described. Methods for introducing unidirectional deletions into a terminal location of a cloned DNA sequence which is inserted into the vector of the present invention are also disclosed. These methods are useful for introducing deletions into either or both ends of a cloned DNA insert, for high throughput sequencing of any DNA of interest.

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

    E-Print Network [OSTI]

    Frey, H. Christopher

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

  3. An environment-mediated quantum deleter

    E-Print Network [OSTI]

    R. Srikanth; Subhashish Banerjee

    2007-04-24T23:59:59.000Z

    Environment-induced decoherence presents a great challenge to realizing a quantum computer. We point out the somewhat surprising fact that decoherence can be useful, indeed necessary, for practical quantum computation, in particular, for the effective erasure of quantum memory in order to initialize the state of the quantum computer. The essential point behind the deleter is that the environment, by means of a dissipative interaction, furnishes a contractive map towards a pure state. We present a specific example of an amplitude damping channel provided by a two-level system's interaction with its environment in the weak Born-Markov approximation. This is contrasted with a purely dephasing, non-dissipative channel provided by a two-level system's interaction with its environment by means of a quantum nondemolition interaction. We point out that currently used state preparation techniques, for example using optical pumping, essentially perform as quantum deleters.

  4. Financial Opportunities Delete Me | Department of Energy

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

    AFDC Printable Version Share this resource Send a link to EERE: Alternative Fuels Data Center Home Page to someone by E-mail Share EERE: Alternative Fuels Data Center Home Page on Facebook Tweet about EERE: Alternative Fuels Data Center Home Page on Twitter Bookmark EERE: Alternative Fuels Data Center Home Page on Google Bookmark EERE: Alternative Fuels DataDepartment of Energy Your Density Isn't YourTransport inEnergy June 6-7, 2013 MeetingEA # 1440 FINALbyFinancial Opportunities Delete

  5. Method for introducing unidirectional nested deletions

    DOE Patents [OSTI]

    Dunn, John J. (Bellport, NY); Quesada, Mark A. (Middle Island, NY); Randesi, Matthew (Upton, NY)

    1999-07-27T23:59:59.000Z

    Disclosed is a method for the introduction of unidirectional deletions in a cloned DNA segment. More specifically, the method comprises providing a recombinant DNA construct comprising a DNA segment of interest inserted in a cloning vector, the cloning vector having an f1 endonuclease recognition sequence adjacent to the insertion site of the DNA segment of interest. The recombinant DNA construct is then contacted with the protein pII encoded by gene II of phage f1 thereby generating a single-stranded nick. The nicked DNA is then contacted with E. coli Exonuclease III thereby expanding the single-stranded nick into a single-stranded gap. The single-stranded gapped DNA is then contacted with a single-strand-specific endonuclease thereby producing a linearized DNA molecule containing a double-stranded deletion corresponding in size to the single-stranded gap. The DNA treated in this manner is then incubated with DNA ligase under conditions appropriate for ligation. Also disclosed is a method for producing single-stranded DNA probes. In this embodiment, single-stranded gapped DNA, produced as described above, is contacted with a DNA polymerase in the presence of labeled nucleotides to fill in the gap. This DNA is then linearized by digestion with a restriction enzyme which cuts outside the DNA segment of interest. The product of this digestion is then denatured to produce a labeled single-stranded nucleic acid probe.

  6. Method for introducing unidirectional nested deletions

    DOE Patents [OSTI]

    Dunn, J.J.; Quesada, M.A.; Randesi, M.

    1999-07-27T23:59:59.000Z

    Disclosed is a method for the introduction of unidirectional deletions in a cloned DNA segment. More specifically, the method comprises providing a recombinant DNA construct comprising a DNA segment of interest inserted in a cloning vector. The cloning vector has an f1 endonuclease recognition sequence adjacent to the insertion site of the DNA segment of interest. The recombinant DNA construct is then contacted with the protein pII encoded by gene II of phage f1 thereby generating a single-stranded nick. The nicked DNA is then contacted with E. coli Exonuclease III thereby expanding the single-stranded nick into a single-stranded gap. The single-stranded gapped DNA is then contacted with a single-strand-specific endonuclease thereby producing a linearized DNA molecule containing a double-stranded deletion corresponding in size to the single-stranded gap. The DNA treated in this manner is then incubated with DNA ligase under conditions appropriate for ligation. Also disclosed is a method for producing single-stranded DNA probes. In this embodiment, single-stranded gapped DNA, produced as described above, is contacted with a DNA polymerase in the presence of labeled nucleotides to fill in the gap. This DNA is then linearized by digestion with a restriction enzyme which cuts outside the DNA segment of interest. The product of this digestion is then denatured to produce a labeled single-stranded nucleic acid probe. 1 fig.

  7. Uterine deletion of Trp53 compromises antioxidant responses in...

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

    clearly understood. From our recent finding that premature decidual senescence with terminal differentiation is a cause of preterm birth in mice with uterine Trp53 deletion,...

  8. Multi-omic data integration links Deleted in Breast Cancer 1...

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

    omic data integration links Deleted in Breast Cancer 1 (DBC1) Degradation to Chromatin Remodeling in Inflammatory Response Multi-omic data integration links Deleted in Breast...

  9. Fitness Uniform Deletion: A Simple Way to Preserve Diversity

    E-Print Network [OSTI]

    Hutter, Marcus

    is the gradual decline in population diversity that tends to occur over time. This can slow a system's progress. In this paper we present the Fitness Uniform Deletion Scheme (FUDS), a simple but somewhat unconventional ap

  10. ISC2005v2.ppt

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

    AFDC Printable Version Share this resource Send a link to EERE: Alternative Fuels Data Center Home Page to someone by E-mail Share EERE: Alternative Fuels Data Center Home Page on Facebook Tweet about EERE: Alternative Fuels Data Center Home Page on Twitter Bookmark EERE: Alternative1 First Use of Energy for All Purposes (Fuel and Nonfuel), 2002; Level: National5Sales for4,645U.S. DOEThe Bonneville PowerCherries 82981-1cnHigh School footballHydrogen andHypernucleiNORTHWESTOffice ofOffice

  11. Find It. Delete It. Protect It. Information Technology Security Strategy

    E-Print Network [OSTI]

    Sheridan, Jennifer

    Find It. Delete It. Protect It. Information Technology Security Strategy Executive Summary The general proposed strategy is to optimize risk management for information security incrementally and over that security will be a process rather than project. Achievement of the goal, optimized risk management

  12. Global Systems-Level Analysis of Hfq and SmpB Deletion Mutants...

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

    Systems-Level Analysis of Hfq and SmpB Deletion Mutants in Salmonella: Implications for Virulence and Global Protein Global Systems-Level Analysis of Hfq and SmpB Deletion Mutants...

  13. How to delete a table? | OpenEI Community

    Open Energy Info (EERE)

    AFDC Printable Version Share this resource Send a link to EERE: Alternative Fuels Data Center Home Page to someone by E-mail Share EERE: Alternative Fuels Data Center Home Page on Facebook Tweet about EERE: Alternative Fuels Data Center Home Page on Twitter Bookmark EERE: Alternative Fuels Data Center Home Page onYou are now leaving Energy.gov You are now leaving Energy.gov You are8COaBulkTransmissionSitingProcess.pdfGetecGtel Jump to:Pennsylvania:County, Wyoming: EnergyCareview|delete a table?

  14. Melanin-binding radiopharmaceuticals

    SciTech Connect (OSTI)

    Packer, S; Fairchild, R G; Watts, K P; Greenberg, D; Hannon, S J

    1980-01-01T23:59:59.000Z

    The scope of this paper is limited to an analysis of the factors that are important to the relationship of radiopharmaceuticals to melanin. While the authors do not attempt to deal with differences between melanin-binding vs. melanoma-binding, a notable variance is assumed. (PSB)

  15. The fork head transcription factor Hcm1p participates in the regulation of SPC110, which encodes the calmodulin-binding protein in the

    E-Print Network [OSTI]

    Davis, Trisha N.

    The fork head transcription factor Hcm1p participates in the regulation of SPC110, which encodes and abolish the ability of Hcm1p to act as a suppressor of calmodulin mutants. The promoter of SPC110 contains a match to the consensus binding site. Deletion of HCM1 does not affect the basal level of SPC110

  16. Enhanced Hydrogen Production in Escherichia coli Through Chemical Mutagenesis, Gene Deletion, and Transposon Mutagenesis

    E-Print Network [OSTI]

    Garzon Sanabria, Andrea Juliana

    2011-08-08T23:59:59.000Z

    ENHANCED HYDROGEN PRODUCTION IN ESCHERICHIA COLI THROUGH CHEMICAL MUTAGENESIS, GENE DELETION, AND TRANSPOSON MUTAGENESIS A Thesis by ANDREA JULIANA GARZON SANABRIA Submitted to the Office of Graduate Studies of Texas A...&M University in partial fulfillment of the requirements for the degree of MASTER OF SCIENCE May 2010 Major Subject: Chemical Engineering ENHANCED HYDROGEN PRODUCTION IN ESCHERICHIA COLI THROUGH CHEMICAL MUTAGENESIS, GENE DELETION...

  17. C-terminal Deletions of the Escherichia coli RecA Protein CHARACTERIZATION OF IN VIVO AND IN VITRO EFFECTS*

    E-Print Network [OSTI]

    Cox, Michael M.

    C-terminal Deletions of the Escherichia coli RecA Protein CHARACTERIZATION OF IN VIVO AND IN VITRO, Madison, Wisconsin 53706 A set of C-terminal deletion mutants of the RecA protein of Escherichia coli. In vivo, the deletion of 13 to 17 C-terminal residues results in increased sensitivity to mitomycin C

  18. Cellulose binding domain proteins

    DOE Patents [OSTI]

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

    1998-01-01T23:59:59.000Z

    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. Cellulose binding domain proteins

    DOE Patents [OSTI]

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

    1998-11-17T23:59:59.000Z

    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.

  20. Type I oculocutaneous albinism (OCA1) associated with a large deletion of the tyrosinase (TYR) gene

    SciTech Connect (OSTI)

    Spritz, R.A.; Wick, P.A.; Holmes, S.A.; Schnur, R.E. [Univ. of Wisconsin, Madison, WI (United States)]|[Children`s Hospital of Philadelphia, PA (United States)

    1994-09-01T23:59:59.000Z

    OCA1 is an autosomal recessive disorder in which the biosynthesis of melanin is reduced or absent in skin, hair, and eyes, due to deficient enzymatic activity of tyrosinase. TYR consists of 5 exons spanning over 65 kb at 11q14-q21. Analyses of TYR in >400 unrelated patients with OCA1 have identified more than 50 different point mutations; however, no large deletions have been detected. Here we report a large deletion of TYR in a Caucasian boy with OCA1B. Simultaneous SSCP/heteroduplex screening and DNA sequence analysis indicated that the patient was apparently homozygous for a previously described TYR mutation, adjacent to the 3` splice site of IVS2 (-7, t{r_arrow}a). To distinguish between possible gene deletion vs. maternal uniparental isodisomy, we characterized several chromosome 11 polymorphisms. Maternal uniparental isodisomy was excluded by the patient`s heterozygosity for alleles at D11S35 (11q21-122) and HBG2 (11p15.5). In addition, the patient failed to inherit paternal alleles at an MboI RFLP in exon 1 of TYR and at a TaqI RFLP in the promoter region of the gene. To detect a possible submicroscopic deletion, we performed quantitative Southern blot hybridization using a full length TYR cDNA. Compared with controls, both the patient and his father appeared deleted for two or three TYR-derived PstI fragments; the two TYRL-derived fragments appeared normal. These data indicate that the patient and his father have a partial TYR deletion, including at least exons 1, 2, and IVS2. Based on the organization of the gene, this deletion is at least 50 kb in size. The patient is thus hemizygous for the maternally-inherited mutation in IVS2, accounting for his OCA1B phenotype.

  1. Production of glycoprotein-deleted rabies viruses for monosynaptic tracing and high-level gene expression in neurons

    E-Print Network [OSTI]

    Wickersham, Ian R.

    Recombinant rabies viruses rendered replication-deficient by the deletion of their envelope glycoprotein gene are useful tools for neuroscientists, permitting (1) extraordinarily high transgene expression levels within ...

  2. Deleting species from model food webs Christopher Quince, Paul G. Higgs and Alan J. McKane

    E-Print Network [OSTI]

    McKane, Alan

    causing extinction of further species from the food web. To investigate these effects we used one species was deleted. On average, only 2.1% of the remaining species went extinct as a result of extinction. The probability of extinction of prey of the deleted species was also significantly higher than

  3. Development/Plasticity/Repair Deletion of ERK2 Mitogen-Activated Protein Kinase

    E-Print Network [OSTI]

    Development/Plasticity/Repair Deletion of ERK2 Mitogen-Activated Protein Kinase Identifies Its Key University, Piscataway, New Jersey 08855-8082 The mitogen-activated protein (MAP) kinases ERK1 and ERK2-specific functions in vivo. We have examined the role of ERK2 in neural development by conditional inactivation

  4. Evaluation of unmarked deletion mutants as improved Brucella vaccine strains in the mouse and goat models

    E-Print Network [OSTI]

    Kahl, Melissa Marie

    2006-10-30T23:59:59.000Z

    and in vitro virulence. Survival and efficacy of these novel deletion mutants were then evaluated in the mouse model. The asp24 mutants, which persist for extended periods in vivo, appear superior as a vaccine candidate compared to approved vaccine strains S19...

  5. The Frequency of DYT1 (GAG Deletion) Mutation in Primary Dystonia Patients from Iran

    E-Print Network [OSTI]

    Boyer, Edmond

    The Frequency of DYT1 (GAG Deletion) Mutation in Primary Dystonia Patients from Iran Mohammad Hamid. Molecular Medicine Division, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran 2. Medical Genetics Department, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran 3

  6. DeltaSky: Optimal Maintenance of Skyline Deletions without Exclusive Dominance Region Generation

    E-Print Network [OSTI]

    Egecioglu, ?mer

    of the so called exclusive dominance region (EDR) to achieve optimal I/O performance for deletion maintenance. However, the shape of an EDR becomes extremely complex in higher dimensions, and algorithms for its computation have not been developed. We derive a systematic way to decompose a d-dimensional EDR

  7. MHC Class II Tetramers and the Pursuit of Antigen-specific T cells: Define, Deviate, Delete

    E-Print Network [OSTI]

    Paris-Sud XI, Universit de

    1 MHC Class II Tetramers and the Pursuit of Antigen-specific T cells: Define, Deviate, Delete Class II tetramers Corresponding Author: Roberto Mallone, MD Benaroya Research Institute at Virginia secretion and proliferation. The advent of MHC Class II tetramers has added a pivotal tool to our research

  8. Synthetic heparin-binding growth factor analogs

    DOE Patents [OSTI]

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

    2007-01-23T23:59:59.000Z

    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.

  9. Cellulose binding domain fusion proteins

    DOE Patents [OSTI]

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

    1998-02-17T23:59:59.000Z

    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.

  10. 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)

    1998-01-01T23:59:59.000Z

    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.

  11. How to recreate a table after deletion | OpenEI Community

    Open Energy Info (EERE)

    AFDC Printable Version Share this resource Send a link to EERE: Alternative Fuels Data Center Home Page to someone by E-mail Share EERE: Alternative Fuels Data Center Home Page on Facebook Tweet about EERE: Alternative Fuels Data Center Home Page on Twitter Bookmark EERE: Alternative Fuels Data Center Home Page onYou are now leaving Energy.gov You are now leaving Energy.gov You are8COaBulkTransmissionSitingProcess.pdfGetecGtel Jump to:Pennsylvania:County, Wyoming: EnergyCareview|delete arecreate

  12. Erythropoietin binding protein from mammalian serum

    DOE Patents [OSTI]

    Clemons, Gisela K. (Berkeley, CA)

    1997-01-01T23:59:59.000Z

    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.

  13. Erythropoietin binding protein from mammalian serum

    DOE Patents [OSTI]

    Clemons, G.K.

    1997-04-29T23:59:59.000Z

    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.

  14. The Insulator Binding Protein CTCF Positions 20 Nucleosomes around Its Binding Sites across the Human

    E-Print Network [OSTI]

    Weng, Zhiping

    The Insulator Binding Protein CTCF Positions 20 Nucleosomes around Its Binding Sites across occupied by the insulator binding protein CTCF across the human genome. These nucleosomes are highly of CTCF function. Citation: Fu Y, Sinha M, Peterson CL, Weng Z (2008) The Insulator Binding Protein CTCF

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

    E-Print Network [OSTI]

    Fisher, Andrew J.

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

  16. X-ray survival characteristics and genetic analysis for nine saccharomyces deletion mutants that show altered radiation sensitivity

    SciTech Connect (OSTI)

    Game, John C.; Williamson, Marsha S.; Baccari, Clelia

    2004-01-07T23:59:59.000Z

    The availability of a genome-wide set of Saccharomyces deletion mutants provides a chance to identify all the yeast genes involved in DNA repair. Using X-rays, we are screening these mutants to identify additional genes that show increased sensitivity to the lethal effects of ionizing radiation. For each mutant identified as sensitive, we are confirming that the sensitivity phenotype co-segregates with the deletion allele and are obtaining multipoint survival-versus-dose assays in at least two haploid and one homozygous diploid strains. We present data for deletion mutants involving the genes DOT1, MDM20, NAT3, SPT7, SPT20, GCN5, HFI1, DCC1 and VID21/EAF1, and discuss their potential roles in repair. Eight of these genes have a clear radiation-sensitive phenotype when deleted, but the ninth, GCN5, has at most a borderline phenotype. None of the deletions confer substantial sensitivity to ultra-violet radiation, although one or two may confer marginal sensitivity. The DOT1 gene is of interest because its only known function is to methylate one lysine residue in the core of the histone H3 protein. We find that histone H3 mutants (supplied by K. Struhl) in which this residue is replaced by other amino-acids are also X-ray sensitive, seeming to confirm that methylation of the lysine-79 residue is required for effective repair of radiation damage.

  17. Synthetic heparin-binding factor analogs

    DOE Patents [OSTI]

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

    2010-04-20T23:59:59.000Z

    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.

  18. Characterizations of exchangeable partitions and random discrete distributions by deletion properties

    E-Print Network [OSTI]

    Gnedin, Alexander; Pitman, Jim

    2009-01-01T23:59:59.000Z

    We prove a long-standing conjecture which characterises the Ewens-Pitman two-parameter family of exchangeable random partitions, plus a short list of limit and exceptional cases, by the following property: for each $n = 2,3, >...$, if one of $n$ individuals is chosen uniformly at random, independently of the random partition $\\pi_n$ of these individuals into various types, and all individuals of the same type as the chosen individual are deleted, then for each $r > 0$, given that $r$ individuals remain, these individuals are partitioned according to $\\pi_r'$ for some sequence of random partitions $(\\pi_r')$ that does not depend on $n$ or $r$. An analogous result characterizes the associated Poisson-Dirichlet family of random discrete distributions by an independence property related to random deletion of a frequency chosen by a size-biased pick. We also survey the regenerative properties of members of the two-parameter family, and settle a question regarding the explicit arrangement of intervals with lengths ...

  19. Chromosome 12p Deletions in TEL-AML1 Childhood Acute Lymphoblastic Leukemia Are Associated with Retrotransposon

    E-Print Network [OSTI]

    California at Berkeley, University of

    Chromosome 12p Deletions in TEL-AML1 Childhood Acute Lymphoblastic Leukemia Are Associated Acute lymphoblastic leukemia is the most common diagnosis in childhood cancer; and f22% of children, Rhode Island Abstract TEL-AML1 (ETV6-RUNX1) is the most common translocation in the childhood leukemias

  20. 3710 McClintock Avenue Induced Seismicity Consortium (ISC)

    E-Print Network [OSTI]

    Southern California, University of

    of environmental safety associated with hydraulic fracturing operations, waste water injection, fluid production critical and under of environmental safety associated with hydraulic fracturing operations, waste water regulatory agency partners. The consortium will support two key integrated programs; 1) advancing geoscience

  1. Induced Seismicity Consortium (ISC) Fred Aminzadeh, PI, Petroleum Engineering Program

    E-Print Network [OSTI]

    Southern California, University of

    modeling and data analysis capabilities for predicting seismic impacts associated with hydraulic fracturing addresses a very critical and under-developed aspect of environmental safety associated with hydraulic fracturing operations waste water injection and disposal wells, geothermal resource development, and EOR/CO2

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

    Open Energy Info (EERE)

    AFDC Printable Version Share this resource Send a link to EERE: Alternative Fuels Data Center Home Page to someone by E-mail Share EERE: Alternative Fuels Data Center Home Page on Facebook Tweet about EERE: Alternative Fuels Data Center Home Page on Twitter Bookmark EERE: Alternative Fuels Data Center Home Page onYou are now leaving Energy.gov You are now leaving Energy.gov You are beingZealand Jump to: navigation, search OpenEIHesperia,IDGWPIndiantown,Innoferm GmbH Jump

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

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

    AFDC Printable Version Share this resource Send a link to EERE: Alternative Fuels Data Center Home Page to someone by E-mail Share EERE: Alternative Fuels Data Center Home Page on Facebook Tweet about EERE: Alternative Fuels Data Center Home Page on Twitter Bookmark EERE: Alternative1 First Use of Energy for All Purposes (Fuel and Nonfuel), 2002; Level: National5Sales for4,645U.S. DOEThe Bonneville PowerCherries 82981-1cnHigh School footballHydrogen andHypernucleiNORTHWESTOffice of

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

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

    AFDC Printable Version Share this resource Send a link to EERE: Alternative Fuels Data Center Home Page to someone by E-mail Share EERE: Alternative Fuels Data Center Home Page on Facebook Tweet about EERE: Alternative Fuels Data Center Home Page on Twitter Bookmark EERE: Alternative1 First Use of Energy for All Purposes (Fuel and Nonfuel), 2002; Level: National5Sales for4,645U.S. DOEThe Bonneville PowerCherries 82981-1cnHigh School footballHydrogen andHypernucleiNORTHWESTOffice ofOffice

  5. ISC15 Workshop for Intel® Xeon Phi

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

    AFDC Printable Version Share this resource Send a link to EERE: Alternative Fuels Data Center Home Page to someone by E-mail Share EERE: Alternative Fuels Data Center Home Page on Facebook Tweet about EERE: Alternative Fuels Data Center Home Page on Twitter Bookmark EERE: Alternative1 First Use of Energy for All Purposes (Fuel and Nonfuel), 2002; Level: National5Sales for4,645U.S. DOEThe Bonneville PowerCherries 82981-1cnHigh School footballHydrogen andHypernucleiNORTHWESTOffice ofOffice

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

    Open Energy Info (EERE)

    AFDC Printable Version Share this resource Send a link to EERE: Alternative Fuels Data Center Home Page to someone by E-mail Share EERE: Alternative Fuels Data Center Home Page on Facebook Tweet about EERE: Alternative Fuels Data Center Home Page on Twitter Bookmark EERE: Alternative Fuels Data Center Home Page onYou are now leaving Energy.gov You are now leaving Energy.gov You are being directedAnnual SiteofEvaluatingGroup | OpenHunan Runhua New Energy

  7. Crystallographic controls on uranyl binding at the quartz/water...

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

    controls on uranyl binding at the quartzwater interface. Abstract: Molecular dynamics methods were used to simulate UO2(OH)20 binding to pairs of oxo sites on three...

  8. Single-Molecule Dynamics Reveals Cooperative Binding-Folding...

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

    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...

  9. Atomic structure of nitrate-binding protein crucial for photosynthetic...

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

    structure of nitrate-binding protein crucial for photosynthetic productivity. Atomic structure of nitrate-binding protein crucial for photosynthetic productivity. Abstract:...

  10. affinity binding studies: Topics by E-print Network

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

    for Ligand Binding Affinity Prediction Chemistry Websites Summary: of the binding free energy between a ligand and a protein is an important component in the virtual...

  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. Effects of Deletions of High Molecular Weight Glutenin Subunit Alleles on Dough Properties and Wheat Flour Tortilla Quality

    E-Print Network [OSTI]

    Tuncil, Yunus

    2012-10-19T23:59:59.000Z

    , Lloyd W. Rooney Dirk B. Hays Intercollegiate Faculty Chair, Alejandro Castillo August 2012 Major Subject: Food Science and Technology iii ABSTRACT Effects of Deletions of High Molecular Weight Glutenin Subunit Alleles on Dough... and opportunities he provided me. I am thankful to my committee members Dr. Lloyd Rooney for his encouragements and Dr. Dirk Hays providing directions. I acknowledge to Dr. Amir Ibrahim for his support and help with statistical analysis and interpretation. I...

  13. Deletion of exon 3 of the insulin receptor gene in a kindred with a familial form of insulin resistance

    SciTech Connect (OSTI)

    Wertheimer, E.; Barbetti, F.; Accili, D.; Taylor, S.I. [National Institutes of Health, Bethesda, MD (United States)] [National Institutes of Health, Bethesda, MD (United States); Litvin, Y.; Ebstein, R.P.; Bennet, E.R.

    1994-05-01T23:59:59.000Z

    Molecular scanning techniques, such as denaturing gradient gel electrophoresis (DGGE), greatly facilitate screening candidate genes for mutations. The authors have used DGGE to screen for mutations in the insulin receptor gene in a family in which four of five daughters were affected by type A insulin resistance in association with acanthosis nigricans and hyperandrogenism. DGGE did not detect mutations in any of the 22 exons of the insulin receptor gene. Nevertheless, Southern blot analysis suggested that there was a deletion of exon 3 in the other paternal allele of the insulin receptor gene. Analysis of the father`s cDNA confirmed that exon 3 was deleted from mRNA molecules derived from one of his two alleles of the insulin receptor gene. Furthermore, the father was found to be hemizygous for a polymorphic sequence (GAC{sup Asp} at codon 234) in exon 3 that was not inherited by any of the five daughters. Instead, all five daughters inherited the paternal allele with the deletion mutation. They did not detect mutations in the mother`s insulin receptor gene. Furthermore, the clinical syndrome did not segregate with either of the mother`s two alleles of the insulin receptor gene. Although the youngest daughter inherited the mutant allele from her father, she was not clinically affected. The explanation for the incomplete penetrance is not known. These results emphasize the importance of specifically searching for deletion mutations when screening candidate genes for mutations. Furthermore, the existence of apparently asymptomatic carriers of mutations in the insulin receptor gene, such as the father in the present study, suggests that the prevalence of mutations in the insulin receptor gene may be higher than would be predicted on the basis of the observed prevalence of patients with extreme insulin resistance. 34 refs., 6 figs., 1 tab.

  14. Unexpected effects of gene deletion on mercury interactions with the methylation-deficient mutant hgcAB

    SciTech Connect (OSTI)

    Lin, Hui [ORNL] [ORNL; Hurt, Jr., Richard Ashley [ORNL; Johs, Alexander [ORNL] [ORNL; Parks, Jerry M [ORNL] [ORNL; Morrell-Falvey, Jennifer L [ORNL] [ORNL; Liang, Liyuan [ORNL] [ORNL; Elias, Dwayne A [ORNL] [ORNL; Gu, Baohua [ORNL] [ORNL

    2014-01-01T23:59:59.000Z

    The hgcA and hgcB gene pair is essential for mercury (Hg) methylation by certain anaerobic bacteria,1 but little is known about how deletion of hgcAB affects cell surface interactions and intracellular uptake of Hg. Here, we compare hgcAB mutants with the wild-type (WT) strains of both Geobacter sulfurreducens PCA and Desulfovibrio desulfuricans ND132 and observe differences in Hg redox transformations, adsorption, and uptake in laboratory incubation studies. In both strains, deletion of hgcAB increased the reduction of Hg(II) but decreased the oxidation of Hg(0) under anaerobic conditions. The measured cellular thiol content in hgcAB mutants was lower than the WT, accounting for decreased adsorption and uptake of Hg. Despite the lack of methylation activity, Hg uptake by the hgcAB continued, albeit at a slower rate than the WT. These findings demonstrate that deletion of the hgcAB gene not only eliminates Hg methylation but also alters cell physiology, resulting in changes to Hg redox reactions, sorption, and uptake by cells.

  15. Hardware device binding and mutual authentication

    DOE Patents [OSTI]

    Hamlet, Jason R; Pierson, Lyndon G

    2014-03-04T23:59:59.000Z

    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.

  16. Bridging the gap between protein-tyrosine phosphorylation networks, metabolism and physiology in liver-specific PTP1b deletion mice

    E-Print Network [OSTI]

    Miraldi, Emily R. (Emily Rae)

    2012-01-01T23:59:59.000Z

    Metabolic syndrome describes a complex set of obesity-related disorders that enhance diabetes, cardiovascular, and mortality risk. Studies of liver-specific protein-tyrosine phosphatase lb (PTPlb) deletion mice (L-PTPlb-/-) ...

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

    DOE Patents [OSTI]

    Mayfield, Stephen P.

    2006-10-17T23:59:59.000Z

    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.

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

    DOE Patents [OSTI]

    Mayfield, Stephen (Cardiff, CA)

    2000-01-01T23:59:59.000Z

    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. Polypyrimidine Track-binding Protein Binding Downstream of Caspase-2 Alternative Exon 9 Represses Its Inclusion*

    E-Print Network [OSTI]

    Wu, Jane Y.

    Polypyrimidine Track-binding Protein Binding Downstream of Caspase-2 Alternative Exon 9 Represses (In100) located in the intron downstream of alternative exon 9. The upstream portion of this element downstream from the decoy 3 acceptor site. This downstream domain harbors several polypyrimidine track

  20. Telegraphic prose: The effects of a subjective deletion scheme on the comprehension and reading rate of blind and sighted students.

    E-Print Network [OSTI]

    Sheffield, Carol Ann

    1972-01-01T23:59:59.000Z

    for a Speci. fied Percentage of Deletion 114 APPENDIX K: Instructions for Phase II ? Passage and Test 115 APPENDIX L: Index of Agreement Among Sighted Ss on the Rank Order of Words Within Each Sentence 119 APPENDIX M: 10, 30, and 50 Percent... Treatment Conditions 50 14 Mean Reading Time (in minutes) and Standard Deviation for Blind and Sighted Ss in Each of the Four Treatment Conditions 51 15 Mean E and Standard Deviation for Blind and Sighted Ss in Each of the Four Treatment Conditions. 53...

  1. 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)

    1996-01-01T23:59:59.000Z

    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.

  2. Binding Energies in Nonrelativistic Field Theories

    E-Print Network [OSTI]

    Andreas S. Kronfeld

    1996-08-26T23:59:59.000Z

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

  3. Nucleic acids encoding a cellulose binding domain

    DOE Patents [OSTI]

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

    1996-03-05T23:59:59.000Z

    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.

  4. Names and Binding in Type Theory

    E-Print Network [OSTI]

    Schpp, Ulrich

    Names and name-binding are useful concepts in the theory and practice of formal systems. In this thesis we study them in the context of dependent type theory. We propose a novel dependent type theory with primitives for the explicit handling...

  5. Impact on the steam electric power industry of deleting Section 316(a) of the Clean Water Act: Capital costs

    SciTech Connect (OSTI)

    Veil, J.A.

    1993-01-01T23:59:59.000Z

    Many power plants discharge large volumes of cooling water. In some cases, the temperature of the discharge exceeds state thermal requirements. Section 316(a) of the Clean Water Act (CWA) allows a thermal discharger to demonstrate that less stringent thermal effluent limitations would still protect aquatic life. About 32% of total US steam electric generating capacity operates under Section 316(a) variances. In 1991, the US Senate proposed legislation that would delete Section 316(a) from the CWA. This study, presented in two companion reports, examines how this legislation would affect the steam electric power industry. This report describes alternatives available to nuclear and coal-fired plants currently operating under variances. Data from 38 plants representing 14 companies are used to estimate the national cost of implementing such alternatives. Although there are other alternatives, most affected plants would be retrofitted with cooling towers. Assuming that all plants currently operating under variances would install cooling towers, the national capital cost estimate for these retrofits ranges from $22.7 billion to $24.4 billion (in 1992 dollars). The second report quantitatively and qualitatively evaluates the energy and environmental impacts of deleting the variance. Little justification has been found for removing the Section 316(a) variance from the CWA.

  6. U-101: Mozilla Firefox / Thunderbird / SeaMonkey XBL Binding...

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

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

  7. acid binding proteins: Topics by E-print Network

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

    The adipocyte fatty acid-binding protein aP2 regulates systemic glucose (more) Shum, Bennett Oh Vic 2007-01-01 2 Fatty acid-binding protein in bovine skeletal muscle Texas A&M...

  8. acid dopac binds: Topics by E-print Network

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

    The adipocyte fatty acid-binding protein aP2 regulates systemic glucose (more) Shum, Bennett Oh Vic 2007-01-01 2 Fatty acid-binding protein in bovine skeletal muscle Texas A&M...

  9. Investigation of metal binding properties in the hairpin ribozyme

    E-Print Network [OSTI]

    Kirchner, Alyson Jane

    2002-01-01T23:59:59.000Z

    independently folding domains, labeled loop A and loop B. Divalent metal ions are thought to bind in specific sites within the structure and promote ribozyme folding, substrate binding, and cleavage. The goals of the present studies are to further clarify...

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

    E-Print Network [OSTI]

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

    2009-12-28T23:59:59.000Z

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

  11. September 18, 1994 A Binding Architecture for Multimedia Networks

    E-Print Network [OSTI]

    Columbia University

    1 September 18, 1994 A Binding Architecture for Multimedia Networks Aurel A. Lazar , Shailendra K of a set of interfaces, methods and primitives. The former abstract the functionalities of multimedia for implementing binding applications. The binding architecture is embedded into a reference model for multimedia

  12. Tight Binding Hamiltonians and Quantum Turing Machines

    E-Print Network [OSTI]

    Paul Benioff

    1996-10-17T23:59:59.000Z

    This paper extends work done to date on quantum computation by associating potentials with different types of computation steps. Quantum Turing machine Hamiltonians, generalized to include potentials, correspond to sums over tight binding Hamiltonians each with a different potential distribution. Which distribution applies is determined by the initial state. An example, which enumerates the integers in succession as binary strings, is analyzed. It is seen that for some initial states the potential distributions have quasicrystalline properties and are similar to a substitution sequence.

  13. Dual chain synthetic heparin-binding growth factor analogs

    DOE Patents [OSTI]

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

    2012-04-24T23:59:59.000Z

    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.

  14. Dual chain synthetic heparin-binding growth factor analogs

    DOE Patents [OSTI]

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

    2009-10-06T23:59:59.000Z

    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.

  15. Deletion of P399{sub E}401 in NADPH cytochrome P450 oxidoreductase results in partial mixed oxidase deficiency

    SciTech Connect (OSTI)

    Flueck, Christa E., E-mail: christa.flueck@dkf.unibe.ch [Pediatric Endocrinology, Diabetology and Metabolism, University Children's Hospital, Bern (Switzerland); Mallet, Delphine [Service d'Endocrinologie Moleculaire et Maladies Rares, Hospices Civils de Lyon, Bron (France)] [Service d'Endocrinologie Moleculaire et Maladies Rares, Hospices Civils de Lyon, Bron (France); Hofer, Gaby [Pediatric Endocrinology, Diabetology and Metabolism, University Children's Hospital, Bern (Switzerland)] [Pediatric Endocrinology, Diabetology and Metabolism, University Children's Hospital, Bern (Switzerland); Samara-Boustani, Dinane [Hopital Necker-Enfants malades, Paris (France)] [Hopital Necker-Enfants malades, Paris (France); Leger, Juliane [Hopital Robert Debre, Paris (France)] [Hopital Robert Debre, Paris (France); Polak, Michel [Hopital Necker-Enfants malades, Paris (France)] [Hopital Necker-Enfants malades, Paris (France); Morel, Yves [Service d'Endocrinologie Moleculaire et Maladies Rares, Hospices Civils de Lyon, Bron (France)] [Service d'Endocrinologie Moleculaire et Maladies Rares, Hospices Civils de Lyon, Bron (France); Pandey, Amit V., E-mail: amit@pandeylab.org [Pediatric Endocrinology, Diabetology and Metabolism, University Children's Hospital, Bern (Switzerland)

    2011-09-09T23:59:59.000Z

    Highlights: {yields} Mutations in human POR cause congenital adrenal hyperplasia. {yields} We are reporting a novel 3 amino acid deletion mutation in POR P399{sub E}401del. {yields} POR mutation P399{sub E}401del decreased P450 activities by 60-85%. {yields} Impairment of steroid metabolism may be caused by multiple hits. {yields} Severity of aromatase inhibition is related to degree of in utero virilization. -- Abstract: P450 oxidoreductase (POR) is the electron donor for all microsomal P450s including steroidogenic enzymes CYP17A1, CYP19A1 and CYP21A2. We found a novel POR mutation P399{sub E}401del in two unrelated Turkish patients with 46,XX disorder of sexual development. Recombinant POR proteins were produced in yeast and tested for their ability to support steroid metabolizing P450 activities. In comparison to wild-type POR, the P399{sub E}401del protein was found to decrease catalytic efficiency of 21-hydroxylation of progesterone by 68%, 17{alpha}-hydroxylation of progesterone by 76%, 17,20-lyase action on 17OH-pregnenolone by 69%, aromatization of androstenedione by 85% and cytochrome c reduction activity by 80%. Protein structure analysis of the three amino acid deletion P399{sub E}401 revealed reduced stability and flexibility of the mutant. In conclusion, P399{sub E}401del is a novel mutation in POR that provides valuable genotype-phenotype and structure-function correlation for mutations in a different region of POR compared to previous studies. Characterization of P399{sub E}401del provides further insight into specificity of different P450s for interaction with POR as well as nature of metabolic disruptions caused by more pronounced effect on specific P450s like CYP17A1 and aromatase.

  16. Autoradiographic localization of endothelin-1 binding sites in porcine skin

    SciTech Connect (OSTI)

    Zhao, Y.D.; Springall, D.R.; Wharton, J.; Polak, J.M. (Royal Postgraduate Medical School, London (England))

    1991-01-01T23:59:59.000Z

    Autoradiographic techniques and {sup 125}I-labeled endothelin-1 were used to study the distribution of endothelin-1 binding sites in porcine skin. Specific endothelin-1 binding sites were localized to blood vessels (capillaries, deep cutaneous vascular plexus, arteries, and arterioles), the deep dermal and connective tissue sheath of hair follicles, sebaceous and sweat glands, and arrector pili muscle. Specific binding was inhibited by endothelin-2 and endothelin-3 as well as endothelin-1. Non-specific binding was found in the epidermis and the medulla of hair follicles. No binding was found in connective tissue or fat. These vascular binding sites may represent endothelin receptors, in keeping with the known cutaneous vasoconstrictor actions of the peptide. If all binding sites are receptors, the results suggest that endothelin could also regulate the function of sweat glands and may have trophic effects in the skin.

  17. Both common variations and rare non-synonymous substitutions and small insertion/deletions in CLU are associated with increased Alzheimer risk

    E-Print Network [OSTI]

    Bettens, Karolien; Brouwers, Nathalie; Engelborghs, Sebastiaan; Lambert, Jean-Charles; Rogaeva, Ekaterina; Vandenberghe, Rik; Le Bastard, Nathalie; Pasquier, Florence; Vermeulen, Steven; Van Dongen, Jasper; Mattheijssens, Maria; Peeters, Karin; Mayeux, Richard; St George-Hyslop, Peter; Amouyel, Philippe; De Deyn, Peter P; Sleegers, Kristel; Van Broeckhoven, Christine

    2012-01-16T23:59:59.000Z

    insertion/deletions. A meta-analysis, combining the datasets of the 3 cohorts with published CLU sequencing data, confirmed that rare coding variations in the CLU ?-chain were significantly enriched in AD patients (ORMH = 1.96 [95% CI = 1.18-3.25]; p = 0...

  18. ANDERSON-TEIXEIRA FINAL PROOF.DOCX (DO NOT DELETE) 3/7/2011 9:29 AM DO BIOFUELS LIFE CYCLE

    E-Print Network [OSTI]

    DeLucia, Evan H.

    ANDERSON-TEIXEIRA FINAL PROOF.DOCX (DO NOT DELETE) 3/7/2011 9:29 AM 589 DO BIOFUELS LIFE CYCLE ANALYSES ACCURATELY QUANTIFY THE CLIMATE IMPACTS OF BIOFUELS-RELATED LAND USE CHANGE? Kristina J. Anderson in determining the sustainability of biofuels. To ensure that legal standards are effective in limiting climate

  19. COII/tRNA[sup Lys] intergenic 9-bp deletion and other mtDNA markers clearly reveal that the Tharus (Southern Nepal) have oriental affinities

    SciTech Connect (OSTI)

    Passarino, G.; Semino, O.; Santachiara-Benerecetti, A.S.; Modiano, G. (Universita di Tor Vergata (Romania))

    1993-09-01T23:59:59.000Z

    The authors searched for the East Asian mtDNA 9-bp deletion in the intergenic COII/tRNA[sup Lys] region in a sample of 107 Tharus (50 from central Terai and 57 from eastern Terai), a population whose anthropological origin has yet to be completely clarified. The deletion, detected by electrophoresis of the PCR-amplified nt 7392-8628 mtDNA fragment after digestion with HaeIII, was found in about 8% of both Tharu groups but was found in none of the 76 Hindus who were examined as a non-Oriental neighboring control population. A complete triplication of the 9-bp unit, the second case so far reported, was also observed in one eastern Tharu. All the mtDNAs with the deletion, and that with the triplication, were further characterized (by PCR amplification of the relevant mTDNA fragments and their digestion with the appropriate enzymes) to locate them in the Ballinger et al. phylogeny of East Asian mtDNA haplotypes. The deletion was found to be associated with four different haplotypes, two of which are reported for the first time. One of the deletions and especially the triplication could be best explained by the assumption of novel length-change events. Ballinger's classification of East Asian mtDNA haplotypes is mainly based on the phenotypes for the DdeI site at nt 10394 and the AluI site at nt 10397. Analysis of the entire Tharu sample revealed that more than 70% of the Tharus have both sites, the association of which has been suggested as an ancient East Asian peculiarity. These results conclusively indicate that the Tharus have a predominantly maternal Oriental ancestry. Moreover, they show at least one and perhaps two further distinct length mutations, and this suggests that the examined region is a hot spot of rearrangements. 21 refs., 5 figs., 6 tabs.

  20. Tight Binding Hamiltonians and Quantum Turing Machines

    SciTech Connect (OSTI)

    Benioff, P. [Physics Division, Argonne National Laboratory, Argonne, Illinois 60439 (United States)] [Physics Division, Argonne National Laboratory, Argonne, Illinois 60439 (United States)

    1997-01-01T23:59:59.000Z

    This paper extends work done to date on quantum computation by association of potentials with different types of steps. Quantum Turing machine Hamiltonians, generalized to include potentials, correspond to sums over tight binding Hamiltonians each with a different potential distribution. Which distribution applies is determined by the initial state. An example, which enumerates the integers in succession as binary strings, is analyzed. It is seen that for some initial states, the potential distributions have quasicrystalline properties and are similar to a substitution sequence. {copyright} {ital 1997} {ital The American Physical Society}

  1. Gene encoding herbicide safener binding protein

    DOE Patents [OSTI]

    Walton, Jonathan D. (East Lansing, MI); Scott-Craig, John S. (East Lansing, MI)

    1999-01-01T23:59:59.000Z

    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.

  2. Polynucleotides encoding TRF1 binding proteins

    DOE Patents [OSTI]

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

    2002-01-01T23:59:59.000Z

    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.

  3. A model for positron binding to polar molecules

    E-Print Network [OSTI]

    Gribakin, G F

    2015-01-01T23:59:59.000Z

    A model for positron binding to polar molecules is considered by combining the dipole potential outside the molecule with a strongly repulsive core of a given radius. Using existing experimental data on binding energies leads to unphysically small core radii for all of the molecules studied. This suggests that electron-positron correlations neglected in the simple model play a large role in determining the binding energy. We account for these by including polarization potential via perturbation theory. The improved model enables reliable predictions of binding energies to be made for a range of polar organic molecules and hydrogen cyanide, whose binding energy is known from accurate quantum chemistry calculations. The model explains the linear dependence of the binding energies on the polarizability inferred from the experimental data [Danielson et al 2009 J. Phys. B: At. Mol. Opt. Phys. 42 235203].

  4. HIV evolution in early infection: selection pressures, patterns of insertion and deletion, and the impact of apobec

    SciTech Connect (OSTI)

    Korber, Bette [Los Alamos National Laboratory; Bhattacharya, Tanmoy [Los Alamos National Laboratory; Giorgi, Elena [Los Alamos National Laboratory; Gaschen, B [Los Alamos National Laboratory; Daniels, M [Los Alamos National Laboratory

    2009-01-01T23:59:59.000Z

    The pattern of viral diversification in newly infected individuals provides information about the host environment and immune responses typically experienced by the newly transmitted virus. For example, sites that tend to evolve rapidly across multiple early-infection patients could be involved in enabling escape from common early immune responses, represent adaptation for rapid growth in a newly infected host, or reversion from less fit forms of the virus that were selected for immune escape in previous hosts. Here we investigated the diversification of HIV -I env coding sequences in 81 very early B SUbtype infections previously shown to have resulted from transmission or expansion of single viruses (n=78) or two closely related viruses (n=3). In these cases the sequence of the infecting virus can be estimated accurately, enabling inference of both the direction of substitutions as well as distinction between insertion and deletion events. By integrating information across multiple acutely infected hosts, we find evidence of adaptive evolution of HIV-1 envand identified a subset of codon sites that diversified more rapidly than can be explained by a model of neutral evolution. Of 24 such rapidly diversifying sites, 14 were either (i) clustered and embedded in CTL epitopes that were verified experimentally or predicted based on the individual's HLA or (ii) in a nucleotide context indicative of APOBEC mediated G-to-A substitutions, despite having excluded heavily hypermutated sequences prior to the analysis. In several cases, a rapidly evolving site was both embedded in an APOBEC motif and in a CTL epitope, suggesting that APOBEC may facilitate early immune escape. Ten rapidly diversifying sites could not be explained by CTL escape or APOBEC hypermutation, including the most frequently mutated site, in the fusion peptide of gp4l. We also examined the distribution, extent, and sequence context of insertions and deletions and provide evidence that the length variation seen in hypervariable loop regions of the envelope glycoprotein is a consequence of selection and not mutational hotspots. These results provide a detailed view of the process of diversification of HIV-1 following transmission.

  5. acid binding protein: Topics by E-print Network

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

    Richardson, Charles C. 17 Acidic pH Changes Receptor Binding Specificity of Helicobacter pylori: a Binary Adhesion Model in which Surface Heat Shock (Stress) Proteins...

  6. Correlation between fundamental binding forces and clinical prognosis...

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

    Atomic force microscopy was used to fish for binding reactions between a fibronectin-coated probe (i.e., substrate simulating an implant device) and each of 15...

  7. Crown Ethers in Graphene Bring Strong, Selective Binding | ornl...

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

    Materials Characterization Crown Ethers in Graphene Bring Strong, Selective Binding November 14, 2014 Schematic showing a graphene sheet containing an array of ideal crown ethers....

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

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

    SHARE Crown Ethers Flatten in Graphene for Strong, Specific Binding ORNL discovery holds potential for separations, sensors, batteries, biotech and more This sheet of graphene...

  9. antigen papillomavirus binding: Topics by E-print Network

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

    specificity, the present set of studies undertook similar goals by Corradin; Jacques M. Chiller 1979-01-01 124 Human Erythrocytes Selectively Bind and Enrich Infectious HIV-1...

  10. antigen binding repertoire: Topics by E-print Network

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

    specificity, the present set of studies undertook similar goals by Corradin; Jacques M. Chiller 1979-01-01 127 Human Erythrocytes Selectively Bind and Enrich Infectious HIV-1...

  11. antigen binds phosphatase: Topics by E-print Network

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

    specificity, the present set of studies undertook similar goals by Corradin; Jacques M. Chiller 1979-01-01 139 Human Erythrocytes Selectively Bind and Enrich Infectious HIV-1...

  12. Binding Energy of d Transition Metals to Alkenes By Wave...

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

    Energy of d Transition Metals to Alkenes By Wave Function Theory and Density Functional Theory. Binding Energy of d Transition Metals to Alkenes By Wave Function Theory...

  13. atomic binding energy: Topics by E-print Network

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

    Calvin W. Johnson; Joshua T. Staker 2012-08-30 2 Estimating ProteinLigand Binding Free Energy: Atomic Solvation Parameters for Partition Coefficient and Biotechnology...

  14. Neptunium Binding Kinetics with Arsenazo(III)

    SciTech Connect (OSTI)

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

    2014-08-01T23:59:59.000Z

    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.

  15. Mutational analysis of the RNA-binding domain of the Prunus necrotic ringspot virus (PNRSV) movement protein reveals its requirement for cell-to-cell movement

    SciTech Connect (OSTI)

    Carmen Herranz, Ma [Instituto de Biologia Molecular y Celular de Plantas (IBMCP), UPV-CSIC, Avda. de los Naranjos, s/n, 46022, Valencia (Spain); Sanchez-Navarro, Jesus-Angel [Instituto de Biologia Molecular y Celular de Plantas (IBMCP), UPV-CSIC, Avda. de los Naranjos, s/n, 46022, Valencia (Spain); Sauri, Ana [Departament de Bioquimica i Biologia Molecular, Universitat de Valencia, E-46100 Burjassot (Spain); Mingarro, Ismael [Departament de Bioquimica i Biologia Molecular, Universitat de Valencia, E-46100 Burjassot (Spain); Pallas, Vicente [Instituto de Biologia Molecular y Celular de Plantas (IBMCP), UPV-CSIC, Avda. de los Naranjos, s/n, 46022, Valencia (Spain)]. E-mail: vpallas@ibmcp.upv.es

    2005-08-15T23:59:59.000Z

    The movement protein (MP) of Prunus necrotic ringspot virus (PNRSV) is required for cell-to-cell movement. MP subcellular localization studies using a GFP fusion protein revealed highly punctate structures between neighboring cells, believed to represent plasmodesmata. Deletion of the RNA-binding domain (RBD) of PNRSV MP abolishes the cell-to-cell movement. A mutational analysis on this RBD was performed in order to identify in vivo the features that govern viral transport. Loss of positive charges prevented the cell-to-cell movement even though all mutants showed a similar accumulation level in protoplasts to those observed with the wild-type (wt) MP. Synthetic peptides representing the mutants and wild-type RBDs were used to study RNA-binding affinities by EMSA assays being approximately 20-fold lower in the mutants. Circular dichroism analyses revealed that the secondary structure of the peptides was not significantly affected by mutations. The involvement of the affinity changes between the viral RNA and the MP in the viral cell-to-cell movement is discussed.

  16. The mitochondrial ND1 m.3337G>A mutation associated to multiple mitochondrial DNA deletions in a patient with Wolfram syndrome and cardiomyopathy

    SciTech Connect (OSTI)

    Mezghani, Najla [Laboratoire de Genetique Moleculaire Humaine, Faculte de Medecine de Sfax, Universite de Sfax (Tunisia)] [Laboratoire de Genetique Moleculaire Humaine, Faculte de Medecine de Sfax, Universite de Sfax (Tunisia); Mnif, Mouna [Service d'endocrinologie, C.H.U. Habib Bourguiba de Sfax (Tunisia)] [Service d'endocrinologie, C.H.U. Habib Bourguiba de Sfax (Tunisia); Mkaouar-Rebai, Emna, E-mail: emna_mkaouar@mail2world.com [Laboratoire de Genetique Moleculaire Humaine, Faculte de Medecine de Sfax, Universite de Sfax (Tunisia)] [Laboratoire de Genetique Moleculaire Humaine, Faculte de Medecine de Sfax, Universite de Sfax (Tunisia); Kallel, Nozha [Service d'endocrinologie, C.H.U. Habib Bourguiba de Sfax (Tunisia)] [Service d'endocrinologie, C.H.U. Habib Bourguiba de Sfax (Tunisia); Salem, Ikhlass Haj [Laboratoire de Genetique Moleculaire Humaine, Faculte de Medecine de Sfax, Universite de Sfax (Tunisia)] [Laboratoire de Genetique Moleculaire Humaine, Faculte de Medecine de Sfax, Universite de Sfax (Tunisia); Charfi, Nadia; Abid, Mohamed [Service d'endocrinologie, C.H.U. Habib Bourguiba de Sfax (Tunisia)] [Service d'endocrinologie, C.H.U. Habib Bourguiba de Sfax (Tunisia); Fakhfakh, Faiza [Laboratoire de Genetique Moleculaire Humaine, Faculte de Medecine de Sfax, Universite de Sfax (Tunisia)] [Laboratoire de Genetique Moleculaire Humaine, Faculte de Medecine de Sfax, Universite de Sfax (Tunisia)

    2011-07-29T23:59:59.000Z

    Highlights: {yields} We reported a patient with Wolfram syndrome and dilated cardiomyopathy. {yields} We detected the ND1 mitochondrial m.3337G>A mutation in 3 tested tissues (blood leukocytes, buccal mucosa and skeletal muscle). {yields} Long-range PCR amplification revealed the presence of multiple mitochondrial deletions in the skeletal muscle. {yields} The deletions remove several tRNA and protein-coding genes. -- Abstract: Wolfram syndrome (WFS) is a rare hereditary disorder also known as DIDMOAD (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness). It is a heterogeneous disease and full characterization of all clinical and biological features of this disorder is difficult. The wide spectrum of clinical expression, affecting several organs and tissues, and the similarity in phenotype between patients with Wolfram syndrome and those with certain types of respiratory chain diseases suggests mitochondrial DNA (mtDNA) involvement in Wolfram syndrome patients. We report a Tunisian patient with clinical features of moderate Wolfram syndrome including diabetes, dilated cardiomyopathy and neurological complications. The results showed the presence of the mitochondrial ND1 m.3337G>A mutation in almost homoplasmic form in 3 tested tissues of the proband (blood leukocytes, buccal mucosa and skeletal muscle). In addition, the long-range PCR amplifications revealed the presence of multiple deletions of the mitochondrial DNA extracted from the patient's skeletal muscle removing several tRNA and protein-coding genes. Our study reported a Tunisian patient with clinical features of moderate Wolfram syndrome associated with cardiomyopathy, in whom we detected the ND1 m.3337G>A mutation with mitochondrial multiple deletions.

  17. Engineering Deletions in the Mg1-Pk1 Gene Cluster of Streptomyces sp. Mg1 to Abolish Production of the Mg1-Pk1 Metabolite

    E-Print Network [OSTI]

    Moisan, Sabrina

    2013-09-25T23:59:59.000Z

    and inserted into the mass spectrometer. The spectrometer is programmed to collect spectra at predefined points in an x-y grid across the sample. The spectra can then be used to construct colorized images.3 Some metabolites, such as chalcomycin produced... ENGINEERING DELETIONS IN THE MG1-PK1 GENE CLUSTER OF STREPTOMYCES sp. MG1 TO ABOLISH PRODUCTION OF THE MG1- PK1 METABOLITE An Undergraduate Research Scholars Thesis by SABRINA MOISAN Submitted to Honors and Undergraduate Research...

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

    E-Print Network [OSTI]

    Caflisch, Amedeo

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

  19. The DNA binding activity of p53 displays reactiondiffusion kinetics

    E-Print Network [OSTI]

    Hinow, Peter

    The DNA binding activity of p53 displays reactiondiffusion kinetics 26th Southeastern 37240 The DNA binding activity of p53 displays reactiondiffusion kinetics p. 1/2 #12;Collaborators, Vanderbilt University Emmanuele DiBenedetto, PhD, Department of Mathematics, Vanderbilt University The DNA

  20. Unexpected Nondissociative Binding of N2O on Oxygen Vacancies...

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

    Nondissociative Binding of N2O on Oxygen Vacancies on a Rutile TiO2(110)-11 . Unexpected Nondissociative Binding of N2O on Oxygen Vacancies on a Rutile TiO2(110)-11 ....

  1. news and views nucleotide binds to the polymerase and

    E-Print Network [OSTI]

    Schedl, Paul

    news and views nucleotide binds to the polymerase and before it is incorporated into DNA. Recent structures of several structurally diverse DNA polymerases complexed to DNA and nucleotide substrates have shown that their active sites adopt a closed conforma- tion upon binding to the correct nucleotide12

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

    SciTech Connect (OSTI)

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

    2013-09-25T23:59:59.000Z

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

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

    SciTech Connect (OSTI)

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

    2008-01-01T23:59:59.000Z

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

  4. DB-PABP: a database of polyanion-binding proteins

    E-Print Network [OSTI]

    Fang, Jianwen; Dong, Yinghua; Slamat-Miller, Nazila; Middaugh, C. Russell

    2007-10-04T23:59:59.000Z

    The interactions between polyanions (PAs) and polyanion-binding proteins (PABPs) have been found to play significant roles in many essential biological processes including intracellular organization, transport and protein folding. Furthermore, many...

  5. Research paper Drug diffusion and binding in ionizable interpenetrating networks

    E-Print Network [OSTI]

    Peppas, Nicholas A.

    Research paper Drug diffusion and binding in ionizable interpenetrating networks from poly) (PVA), poly(acrylic acid) (PAA), and their interpenetrating networks (IPNs) were prepared using by measuring their equilibrium polymer volume fraction, equilibrium swelling ratio, and mesh size. Drug

  6. Original article Distribution of endogenous retinoids, retinoid binding

    E-Print Network [OSTI]

    Paris-Sud XI, Universit de

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

  7. Understanding regulation of mRNA by RNA binding proteins

    E-Print Network [OSTI]

    Robertson, Alexander De Jong

    2014-01-01T23:59:59.000Z

    Posttranscriptional regulation of mRNA by RNA-binding proteins plays key roles in regulating the transcriptome over the course of development, between tissues and in disease states. The specific interactions between mRNA ...

  8. acid inhibitor binding: Topics by E-print Network

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

    of correctly predicted inter- face residues in actual interface residues Zhou, Yaoqi 162 Sm-like protein Hfq: Location of the ATP-binding site and the effect of ATP on HfqRNA...

  9. atp binding protein: Topics by E-print Network

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

    corroborate asymmetry of catalysis in F0F1-ATP synthase. Zarrabi, Nawid; Diez, Manuel; Graeber, Peter; Wrachtrup, Joerg; Boersch, Michael 2007-01-01 408 Interplay of pH and Binding...

  10. Metal binding proteins, recombinant host cells and methods

    DOE Patents [OSTI]

    Summers, Anne O.; Caguiat, Jonathan J.

    2004-06-15T23:59:59.000Z

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

  11. angiotensin binding site: Topics by E-print Network

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

    Ser-142 (14). Ser-129 is believed to be a substrate for glycogen synthase kinase 3 Brownfield, Mark S. 55 Similarity Analysis of Protein Binding Sites: A Generalization of the...

  12. antigen binding site: Topics by E-print Network

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

    Ser-142 (14). Ser-129 is believed to be a substrate for glycogen synthase kinase 3 Brownfield, Mark S. 69 Similarity Analysis of Protein Binding Sites: A Generalization of the...

  13. alcohol binding sites: Topics by E-print Network

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

    Ser-142 (14). Ser-129 is believed to be a substrate for glycogen synthase kinase 3 Brownfield, Mark S. 56 Similarity Analysis of Protein Binding Sites: A Generalization of the...

  14. albumin binding sites: Topics by E-print Network

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

    Ser-142 (14). Ser-129 is believed to be a substrate for glycogen synthase kinase 3 Brownfield, Mark S. 54 Similarity Analysis of Protein Binding Sites: A Generalization of the...

  15. anesthetic binding site: Topics by E-print Network

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

    Ser-142 (14). Ser-129 is believed to be a substrate for glycogen synthase kinase 3 Brownfield, Mark S. 57 Similarity Analysis of Protein Binding Sites: A Generalization of the...

  16. acid binding sites: Topics by E-print Network

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

    Ser-142 (14). Ser-129 is believed to be a substrate for glycogen synthase kinase 3 Brownfield, Mark S. 82 Similarity Analysis of Protein Binding Sites: A Generalization of the...

  17. aml-1 binding site: Topics by E-print Network

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

    Ser-142 (14). Ser-129 is believed to be a substrate for glycogen synthase kinase 3 Brownfield, Mark S. 55 Similarity Analysis of Protein Binding Sites: A Generalization of the...

  18. affinity binding sites: Topics by E-print Network

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

    Ser-142 (14). Ser-129 is believed to be a substrate for glycogen synthase kinase 3 Brownfield, Mark S. 112 Similarity Analysis of Protein Binding Sites: A Generalization of the...

  19. antagonist binding sites: Topics by E-print Network

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

    Ser-142 (14). Ser-129 is believed to be a substrate for glycogen synthase kinase 3 Brownfield, Mark S. 58 Similarity Analysis of Protein Binding Sites: A Generalization of the...

  20. alcohol binding site: Topics by E-print Network

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

    Ser-142 (14). Ser-129 is believed to be a substrate for glycogen synthase kinase 3 Brownfield, Mark S. 56 Similarity Analysis of Protein Binding Sites: A Generalization of the...

  1. androgen binding protein: Topics by E-print Network

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

    Ser-142 (14). Ser-129 is believed to be a substrate for glycogen synthase kinase 3 Brownfield, Mark S. 135 A High-Throughput Solid-Phase Microplate Protein-Binding Assay to...

  2. antidepressant binding site: Topics by E-print Network

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

    Ser-142 (14). Ser-129 is believed to be a substrate for glycogen synthase kinase 3 Brownfield, Mark S. 55 Similarity Analysis of Protein Binding Sites: A Generalization of the...

  3. antibody binding site: Topics by E-print Network

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

    Ser-142 (14). Ser-129 is believed to be a substrate for glycogen synthase kinase 3 Brownfield, Mark S. 75 Binding of HIV-1 gp41-Directed Neutralizing and Non-Neutralizing...

  4. autoantibody binding site: Topics by E-print Network

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

    Ser-142 (14). Ser-129 is believed to be a substrate for glycogen synthase kinase 3 Brownfield, Mark S. 56 Similarity Analysis of Protein Binding Sites: A Generalization of the...

  5. atp binding site: Topics by E-print Network

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

    Ser-142 (14). Ser-129 is believed to be a substrate for glycogen synthase kinase 3 Brownfield, Mark S. 90 Similarity Analysis of Protein Binding Sites: A Generalization of the...

  6. auxin binding protein: Topics by E-print Network

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

    Ser-142 (14). Ser-129 is believed to be a substrate for glycogen synthase kinase 3 Brownfield, Mark S. 150 A High-Throughput Solid-Phase Microplate Protein-Binding Assay to...

  7. acid binding site: Topics by E-print Network

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

    Ser-142 (14). Ser-129 is believed to be a substrate for glycogen synthase kinase 3 Brownfield, Mark S. 82 Similarity Analysis of Protein Binding Sites: A Generalization of the...

  8. androgen binding sites: Topics by E-print Network

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

    Ser-142 (14). Ser-129 is believed to be a substrate for glycogen synthase kinase 3 Brownfield, Mark S. 55 Similarity Analysis of Protein Binding Sites: A Generalization of the...

  9. affinity binding site: Topics by E-print Network

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

    Ser-142 (14). Ser-129 is believed to be a substrate for glycogen synthase kinase 3 Brownfield, Mark S. 112 Similarity Analysis of Protein Binding Sites: A Generalization of the...

  10. a1 binding site: Topics by E-print Network

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

    Ser-142 (14). Ser-129 is believed to be a substrate for glycogen synthase kinase 3 Brownfield, Mark S. 59 Similarity Analysis of Protein Binding Sites: A Generalization of the...

  11. amp binding proteins: Topics by E-print Network

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

    Ser-142 (14). Ser-129 is believed to be a substrate for glycogen synthase kinase 3 Brownfield, Mark S. 4 Volume 159, number 1,2 FEBS 0638 August 1983 Specific DNA binding of the...

  12. agonist binding site: Topics by E-print Network

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

    Ser-142 (14). Ser-129 is believed to be a substrate for glycogen synthase kinase 3 Brownfield, Mark S. 62 Similarity Analysis of Protein Binding Sites: A Generalization of the...

  13. assisted binding site: Topics by E-print Network

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

    Ser-142 (14). Ser-129 is believed to be a substrate for glycogen synthase kinase 3 Brownfield, Mark S. 54 Similarity Analysis of Protein Binding Sites: A Generalization of the...

  14. allosteric binding sites: Topics by E-print Network

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

    Ser-142 (14). Ser-129 is believed to be a substrate for glycogen synthase kinase 3 Brownfield, Mark S. 68 Similarity Analysis of Protein Binding Sites: A Generalization of the...

  15. allosteric binding site: Topics by E-print Network

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

    Ser-142 (14). Ser-129 is believed to be a substrate for glycogen synthase kinase 3 Brownfield, Mark S. 68 Similarity Analysis of Protein Binding Sites: A Generalization of the...

  16. activator inhibitor-1 binding: Topics by E-print Network

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

    Ser-142 (14). Ser-129 is believed to be a substrate for glycogen synthase kinase 3 Brownfield, Mark S. 147 Stress modulation of visuomotor binding CiteSeer Summary: The primate...

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

    E-Print Network [OSTI]

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

    2014-11-26T23:59:59.000Z

    in optical thickness of the sensor tip. Cortisol was immobilised on the biosensor tip surface by forming an adduct of hydrocortisone 21-hemisuccinate and a pentylamine-biotin linker through an amide bond, then allowing the biotin moiety on this cortisol... adduct to bind to the streptavidin-conjugated biosensor tip. The cortisol- Towards Engineering Hormone-Binding Globulins as Drug Delivery Agents PLOS ONE | DOI:10.1371/journal.pone.0113402 November 26, 2014 4 / 21 conjugated sensors were immersed...

  18. MANAGING TIGHT BINDING RECEPTORS FOR NEW SPEARATIONS TECHNOLOGIES

    SciTech Connect (OSTI)

    DARYLE H BUSCH RICHARD S GIVENS

    2004-12-10T23:59:59.000Z

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

  19. Clonal deletion of self-reactive T cells in irradiation bone marrow chimeras and neonatally tolerant mice. Evidence for intercellular transfer of Mlsa

    SciTech Connect (OSTI)

    Speiser, D.E.; Schneider, R.; Hengartner, H.; MacDonald, H.R.; Zinkernagel, R.M. (Univ. Hospital, Zuerich (Switzerland))

    1989-08-01T23:59:59.000Z

    Tolerance to Mlsa has been shown to be associated with clonal deletion of cells carrying TCR beta chain variable regions V beta 6 or V beta 8.1 in mice possessing I-E antigens. To evaluate the rules of tolerance induction to Mlsa we prepared irradiation bone marrow chimeras expressing Mlsa or Mlsb and I-E by different cell types. Deletion of V beta 6+, Mlsa-reactive T cells required the presence of Mlsa and I-E products either on bone marrow-derived cells or on irradiated recipient cells. Tolerance was induced when Mlsa and I-E were expressed by distinct cells of the chimera. Also neonatally tolerized mice exhibited depletion of V beta 6+ cells after injection of I-E- Mlsa spleen cells (DBA/1) into newborn I-E+ Mlsb mice (BALB/c x B10.G)F1. These results suggest that the product of the Mlsa locus is soluble and/or may be transferred from cell to cell and bound to I-E antigens. The chimera experiments also showed that tolerance to Mlsa is H-2 allele independent, i.e., is apparently unrestricted. Differentiation of chimeric (H-2d/Mlsa x H-2q/Mlsb)F1 stem cells in either an H-2d or an H-2q thymus revealed that tolerance assessed by absence of V beta 6+ T cells is not dependent on the thymically determined restriction specificity of T cells.

  20. Changes in misonidazole binding with hypoxic fraction in mouse tumors

    SciTech Connect (OSTI)

    Hirst, D.G.; Hazlehurst, J.L.; Brown, J.M.

    1985-07-01T23:59:59.000Z

    Binding of misonidazole (MISO) or a derivative to hypoxic cells in tumors has been proposed as a method for identifying tumors, and measuring their level of hypoxia. The author has recently shown that the hypoxic fraction of tumor cells can be altered over a wide range in vivo by acutely changing the hematocrit of the host animal by transfusion. The present study is aimed to investigate the changes in binding by /sup 14/C MISO that accompanied this procedure. Tumor bearing mice were injected with /sup 14/C MISO, irradiated with a single dose of X rays (20 Gy) and their tumor excised and bisected. One half of each tumor was used to determine cell survival in vitro, the other was used for /sup 14/C scintillation counting. As previously described, tumor cell survival was dramatically increased in acutely anemic mice and this was accompanied by an increase in /sup 14/C MISO binding to the tumors. The relationship between clonogenic cell survival and binding was found to be linear on a log-log plot for each of the tumor lines studied, but the slopes of the lines were different in different tumor lines and generally steeper than the value of 1.0 expected for a 1:1 correspondence between cells binding radioactivity and radiobiological resistance.

  1. Acid Gas Capture Using CO2-Binding Organic Liquids

    SciTech Connect (OSTI)

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

    2010-11-10T23:59:59.000Z

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

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

    E-Print Network [OSTI]

    Lohman, Timothy M.

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

  3. Accurate nuclear radii and binding energies from a chiral interaction

    E-Print Network [OSTI]

    Ekstrom, A; Wendt, K A; Hagen, G; Papenbrock, T; Carlsson, B D; Forssen, C; Hjorth-Jensen, M; Navratil, P; Nazarewicz, W

    2015-01-01T23:59:59.000Z

    The accurate reproduction of nuclear radii and binding energies is a long-standing challenge in nuclear theory. To address this problem two-nucleon and three-nucleon forces from chiral effective field theory are optimized simultaneously to low-energy nucleon-nucleon scattering data, as well as binding energies and radii of few-nucleon systems and selected isotopes of carbon and oxygen. Coupled-cluster calculations based on this interaction, named NNLOsat, yield accurate binding energies and radii of nuclei up to 40Ca, and are consistent with the empirical saturation point of symmetric nuclear matter. In addition, the low-lying collective 3- states in 16O and 40Ca are described accurately, while spectra for selected p- and sd-shell nuclei are in reasonable agreement with experiment.

  4. Molecular Cell High-Affinity Binding of Chp1 Chromodomain

    E-Print Network [OSTI]

    Halazonetis, Thanos

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

  5. 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)

    1999-01-01T23:59:59.000Z

    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.

  6. Workshop on gate valve pressure locking and thermal binding

    SciTech Connect (OSTI)

    Brown, E.J.

    1995-07-01T23:59:59.000Z

    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.

  7. Experimental study of exiton binding energy in semiconducting carbon nanotubes

    E-Print Network [OSTI]

    Maruyama, Shigeo

    and Technology (AIST), Tsukuba 305-8565, Japan 3 Global Edge Institute, Tokyo Institute of Technology, Tokyo, Japan 4 Departement of Mechanical Engineering, The University of Tokyo, Tokyo, Japan (Dated: July 21 dimensional nanotube leads to strong electron-hole localiza- tion, with binding energy as high as 0.5 e

  8. Parkin Binds to / Tubulin and Increases their Ubiquitination and Degradation

    E-Print Network [OSTI]

    Feng, Jian

    Parkin Binds to / Tubulin and Increases their Ubiquitination and Degradation Yong Ren, Jinghui Zhao depolymerize microtubules and increase tubulin degradation. Microtu- bules are polymers of tubulin. Misfolded tubulin monomers are highly toxic and quickly degraded through a hitherto unknown mechanism. Here

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

    DOE Patents [OSTI]

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

    1999-01-05T23:59:59.000Z

    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.

  10. 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)

    1997-01-01T23:59:59.000Z

    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.

  11. Knowledge and Obedience: The Developmental Status of the Binding Theory

    E-Print Network [OSTI]

    Grimshaw, Jane; Rosen, Sara Thomas

    1990-04-05T23:59:59.000Z

    counterpart of sentences like Johnt tM Bill to shave him,. Thi binding relation is generally judged as ungrammatical, yet speakers preferred this interpretation to one in which the pronoun had no antecedent. K N O W I . h D O Ii A N D O B H D I H N C H 203...

  12. Thesis and Dissertation Archiving and Binding Request Form

    E-Print Network [OSTI]

    Bieber, Michael

    Thesis and Dissertation Archiving and Binding Request Form The Van Houten Library's digital copy is for archival purposes which will be accessible through NJIT's Electronic Theses & Dissertations website approved Master's Thesis or Doctoral Dissertation before it can be forwarded by the Graduate Studies Office

  13. Methods of use of cellulose binding domain proteins

    DOE Patents [OSTI]

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

    1997-09-23T23:59:59.000Z

    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.

  14. Off-Shell NN Potential and Triton Binding Energy

    E-Print Network [OSTI]

    Y. Song; R. Machleidt

    1994-03-31T23:59:59.000Z

    The NONLOCAL Bonn-B potential predicts 8.0 MeV binding energy for the triton (in a charge-dependent 34-channel Faddeev calculation) which is about 0.4 MeV more than the predictions by LOCAL NN potentials. We pin down origin and size of the nonlocality in the Bonn potential, in analytic and numeric form. The nonlocality is due to the use of the correct off-shell Feynman amplitude of one-boson-exchange avoiding the commonly used on-shell approximations which yield the local potentials. We also illustrate how this off-shell behavior leads to more binding energy. We emphasize that the increased binding energy is not due to on-shell differences (differences in the fit of the NN data or phase shifts). In particular, the Bonn-B potential reproduces accurately the $\\epsilon_1$ mixing parameter up to 350 MeV as determined in the recent Nijmegen multi-energy NN phase-shift analysis. Adding the relativistic effect from the relativistic nucleon propagators in the Faddeev equations, brings the Bonn-B result up to 8.2 MeV triton binding. This leaves a difference of only 0.3 MeV to experiment, which may possibly be explained by refinements in the treatment of relativity and the inclusion of other nonlocalities (e.~g., quark-gluon exchange at short range). Thus, it is conceivable that a realistic NN potential which describes the NN data up to 300 MeV correctly may explain the triton binding energy without recourse to 3-N forces; relativity would play a major role for this result.

  15. Computer Forensics: you can hide but you canComputer Forensics: you can hide but you can''t deletet delete Dr. Nazli Hardy, 2009Reference: Computer Forensics: Principles and Practice

    E-Print Network [OSTI]

    Hardy, Christopher R.

    1 Computer Forensics: you can hide but you canComputer Forensics: you can hide but you can''t deletet delete Dr. Nazli Hardy, 2009Reference: Computer Forensics: Principles and Practice Volonino Anzaldua Godwin Computer Forensics April 10, 2009 Presentation for Dr. Maria Schiza's Forensics class

  16. DOI: 10.1002/cbic.200500285 Binding of Helix-Threading Peptides to E. coli

    E-Print Network [OSTI]

    Beal, Peter A.

    ] To further explore and develop the capabilities of the HTP design for binding RNA selectively, we identified duplex grooves. To further explore and develop the capabili- ties of the HTP design for binding RNA

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

    E-Print Network [OSTI]

    Adhikari, Sean

    2006-10-30T23:59:59.000Z

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

  18. 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...

  19. Characterization of Mg Binding to the DNA Repair ProteinApurinic...

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

    Mg Binding to the DNA Repair Protein ApurinicApyrimidic Endonuclease 1 via Solid-State Mg NMR Spectroscopy. Characterization of Mg Binding to the DNA Repair Protein Apurinic...

  20. acid-binding protein genes: Topics by E-print Network

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

    The adipocyte fatty acid-binding protein aP2 regulates systemic glucose (more) Shum, Bennett Oh Vic 2007-01-01 2 Fatty acid-binding protein in bovine skeletal muscle Texas A&M...

  1. aberrant fatty acid-binding: Topics by E-print Network

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

    The adipocyte fatty acid-binding protein aP2 regulates systemic glucose (more) Shum, Bennett Oh Vic 2007-01-01 2 Fatty acid-binding protein in bovine skeletal muscle Texas A&M...

  2. acid-binding protein ii: Topics by E-print Network

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

    The adipocyte fatty acid-binding protein aP2 regulates systemic glucose (more) Shum, Bennett Oh Vic 2007-01-01 2 Fatty acid-binding protein in bovine skeletal muscle Texas A&M...

  3. acid-binding immunoglobulin-like lectin-6: Topics by E-print...

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

    The adipocyte fatty acid-binding protein aP2 regulates systemic glucose (more) Shum, Bennett Oh Vic 2007-01-01 2 Fatty acid-binding protein in bovine skeletal muscle Texas A&M...

  4. Nucleon binding corrections to lepton-nucleus deep inelastic scattering: Use of a realistic spectral function

    SciTech Connect (OSTI)

    Dieperink, A.E.L.; Miller, G.A. (Department of Physics, FM-15, University of Washington, Seattle, Washington (USA))

    1991-08-01T23:59:59.000Z

    Nuclear spectral functions computed with realistic nuclear forces are used to compute mean separation energies and to estimate the binding corrections to lepton-nucleus deep inelastic scattering. The separation energies are large and significant binding effects are obtained.

  5. A familial {open_quotes}balanced{close_quotes} 3;9 translocation with cryptic 8q insertion leading to deletion and duplication of 9p23 loci in siblings

    SciTech Connect (OSTI)

    Wagstaff, J.; Hemann, M. [Harvard Medical School, Boston, MA (United States)

    1995-01-01T23:59:59.000Z

    A child with phenotypic features of the 9p{sup {minus}} syndrome, including metopic craniosynostosis, small ears, abdominal wall defect, and mental retardation, as well as hypopigmentation, was found to have a cytogenetically balanced 3;9 translocation, with breakpoints at 3p11 and 9p23, inherited from his phenotypically normal father. Molecular analysis showed heterozygous deletion of the TYRP (tyrosinase-related protein) locus, as well as loci D9S157, D9S274, D9S268, and D9S267, in the child but in neither parent. FISH analysis of the proband`s father indicated that loci deleted in his son, including TYRP, were present on neither the der(3) nor the der(9) translocation products but had been inserted into the long arm of chromosome 8. Therefore, the apparent deletion of these loci in the proband was the result of meiotic segregation of the father`s 3;9 translocation chromosomes together with his normal chromosome 8 (not bearing the insertion from 9p23). Neither the deletion of these 9p23 loci from the translocation chromosomes nor their insertion into 8q was detectable by standard chromosome banding techniques. The proband`s sister exhibited speech delay, mild facial dysmorphism, and renal malformation, and her karyotype was 46,XX. Molecular analysis showed that she had inherited normal chromosomes 3 and 9, as well as the chromosome 8 with the insertion of 9p23 material, from her father. This analysis illustrates a new mechanism to explain cases in which an apparently balanced translocation has been transmitted from a normal parent to a child with a phenotypic abnormality: submicroscopic deletion of material from the translocation breakpoint and insertion into a third chromosome in the balanced parent, with meiotic segregation leading to loss of the inserted material in the child. 36 refs., 9 figs., 1 tab.

  6. 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 (GSKPA)

    2014-10-02T23:59:59.000Z

    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.

  7. Delivering Heparin-Binding Insulin-Like Growth Factor 1 with Self-Assembling Peptide Hydrogels

    E-Print Network [OSTI]

    Miller, Rachel E.

    Heparin-binding insulin-like growth factor 1 (HB-IGF-1) is a fusion protein of IGF-1 with the HB domain of heparin-binding epidermal growth factor-like growth factor. A single dose of HB-IGF-1 has been shown to bind ...

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

    E-Print Network [OSTI]

    Texas at Austin. University of

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

  9. DNA binding shifts the redox potential of the transcription factor SoxR

    E-Print Network [OSTI]

    Dietrich, Lars

    DNA binding shifts the redox potential of the transcription factor SoxR Alon A. Gorodetsky , Lars E-modified electrodes are used to probe the effects of binding to DNA on the redox potential of SoxR, a transcription in the absence of DNA. Using Redmond red as a covalently bound redox reporter affixed above the SoxR binding site

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

    E-Print Network [OSTI]

    Weston, Ken

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

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

    E-Print Network [OSTI]

    Caflisch, Amedeo

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

  12. Molecular dissection of the roles of nucleotide binding and hydrolysis in dynein's AAA domains

    E-Print Network [OSTI]

    Vale, Ronald D.

    Molecular dissection of the roles of nucleotide binding and hydrolysis in dynein's AAA domains (ATPase associated with various cellular activities) domains that are thought to bind nucleotide; the role of nucleotide binding and hydrolysis in each of these four AAA domains has constituted an important and unre

  13. Origin of the Variation of Exciton Binding Energy in Semiconductors Marc Dvorak,1

    E-Print Network [OSTI]

    Wu, Zhigang

    Origin of the Variation of Exciton Binding Energy in Semiconductors Marc Dvorak,1 Su-Huai Wei,2, and the exciton binding energy Eb in technologically important semiconductors varies from merely a few me between the electronic band structures and exciton binding energies in semiconductors, employing first

  14. Improved value for the silicon free exciton binding energy

    SciTech Connect (OSTI)

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

    2013-11-15T23:59:59.000Z

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

  15. A new phenomenological formula for ground state binding energies

    E-Print Network [OSTI]

    G. Gangopadhyay

    2010-07-09T23:59:59.000Z

    A phenomenological formula based on liquid drop model has been proposed for ground state binding energies of nuclei. The effect due to bunching of single particle levels has been incorporated through a term resembling the one-body Hamiltonian. The effect of n-p interaction has been included through a function of valence nucleons. A total of 50 parameters has been used in the present calculation. The r.m.s. deviation for the binding energy values for 2140 nuclei comes out to be 0.376 MeV, and that for 1091 alpha decay energies is 0.284 MeV. The correspondence with the conventional liquid drop model is discussed.

  16. Uranium Exerts Acute Toxicity by Binding to Pyrroloquinoline Quinone Cofactor

    SciTech Connect (OSTI)

    Michael R. VanEngelen; Robert I. Szilagyi; Robin Gerlach; Brady E. Lee; William A. Apel; Brent M. Peyton

    2011-02-01T23:59:59.000Z

    Uranium as an environmental contaminant has been shown to be toxic to eukaryotes and prokaryotes; however, no specific mechanisms of uranium toxicity have been proposed so far. Here a combination of in vivo, in vitro, and in silico studies are presented describing direct inhibition of pyrroloquinoline quinone (PQQ)-dependent growth and metabolism by uranyl cations. Electrospray-ionization mass spectroscopy, UV-vis optical spectroscopy, competitive Ca2+/uranyl binding studies, relevant crystal structures, and molecular modeling unequivocally indicate the preferred binding of uranyl simultaneously to the carboxyl oxygen, pyridine nitrogen, and quinone oxygen of the PQQ molecule. The observed toxicity patterns are consistent with the biotic ligand model of acute metal toxicity. In addition to the environmental implications, this work represents the first proposed molecular mechanism of uranium toxicity in bacteria, and has relevance for uranium toxicity in many living systems.

  17. Nuclear binding, correlations and the origin of EMC effect

    E-Print Network [OSTI]

    Omar Benhar; Ingo SIck

    2012-07-19T23:59:59.000Z

    Recent data for the slope of the EMC-ratio in the intermediate $x$-region for {\\em light} nuclei, with $3 \\leq A \\leq 12$, have the potential to shed new light on the origin of the EMC effect. Here we study the role of nuclear binding using the scaling variable ${\\tilde y}$, best suited to take into account this effect, and the understanding of the average nucleon removal energies, $\\bar{E}$, provided by state-of-the-art calculations based on nuclear many body theory. We find an excellent correlation between the new EMC data at $x \\sim 0.5$ and $\\bar{E}$ for nuclei with $A$ from 3 to $\\infty$, indicating that in this $x$ region binding is an important ingredient to explain the EMC effect. The role played by nucleon-nucleon correlations in this context is also discussed.

  18. Nuclear binding, correlations and the origin of EMC effect

    E-Print Network [OSTI]

    Benhar, Omar

    2012-01-01T23:59:59.000Z

    Recent data for the slope of the EMC-ratio in the intermediate $x$-region for {\\em light} nuclei, with $3 \\leq A \\leq 12$, have the potential to shed new light on the origin of the EMC effect. Here we study the role of nuclear binding using the scaling variable ${\\tilde y}$, best suited to take into account this effect, and the understanding of the average nucleon removal energies, $\\bar{E}$, provided by state-of-the-art calculations based on nuclear many body theory. We find an excellent correlation between the new EMC data at $x \\sim 0.5$ and $\\bar{E}$ for nuclei with $A$ from 3 to $\\infty$, indicating that in this $x$ region binding is an important ingredient to explain the EMC effect. The role played by nucleon-nucleon correlations in this context is also discussed.

  19. ATM Networking in Linux Bindings occur at four distinct times

    E-Print Network [OSTI]

    Westall, James M.

    the following call: sock_register(pvc_proto_ops.family, &pvc_proto_ops); Family is PF_ATMPVC (as in PF_INET) pvc_len); : For ATM PVCs the structure is filled in as follows: static struct proto_ops pvc_proto_ops = { PF_ATMPVC, atm_create, pvc_dup, atm_release, pvc_bind, pvc_connect, : · The entry point addresses

  20. ATM Networking in Linux Bindings occur at four distinct times

    E-Print Network [OSTI]

    Westall, James M.

    using the following call: sock_register(pvc_proto_ops.family, &pvc_proto_ops); Family is PF_ATMPVC (as in PF_INET) pvc_proto_ops is a table of entry point addresses: struct proto_ops { int family; int_ops pvc_proto_ops = { PF_ATMPVC, atm_create, pvc_dup, atm_release, pvc_bind, pvc_connect, : . The entry

  1. Novel binding mechanism for ultra-long range molecules

    E-Print Network [OSTI]

    V. Bendkowsky; B. Butscher; J. Nipper; J. P. Shaffer; R. Loew; T. Pfau

    2008-09-17T23:59:59.000Z

    Molecular bonds can be divided into four primary types: ionic, covalent, van der Waals and hydrogen bonds. At ultralow temperatures a novel binding type emerges paving the way for novel molecules and ultracold chemistry [1,2]. The underlying mechanism for this new type of chemical bond is low-energy electron scattering of Rydberg electrons from polarisable ground state atoms [3]. This quantum scattering process can generate an attractive potential that is able to bind the ground state atom to the Rydberg atom at a well localized position within the Rydberg electron wave function. The resulting giant molecules can have an internuclear separation of several thousand Bohr radii, which places them among the largest known molecules to date. Their binding energies are much smaller than the Kepler frequencies of the Rydberg electrons i.e. the atomic Rydberg electron state is essentially unchanged by the bound ground state atom. Ultracold and dense samples of atoms enable the creation of these molecules via Rydberg excitation. In this paper we present spectroscopic evidence for the vibrational ground and first excited state of a Rubidium dimer Rb(5S)-Rb(nS). We apply a Born-Oppenheimer model to explain the measured binding energies for principal quantum numbers n between 34 and 40 and extract the s-wave scattering length for electron-Rb(5S) scattering in the relevant low energy regime Ekin < 100 meV. We also determine the lifetimes and the polarisabilities of these molecules. P-wave bound states [2], Trimer states [4] as well as bound states for large angular momentum of the Rydberg electron - socalled trilobite molecules [1] - are within reach in the near future and will further refine our conceptual understanding of the chemical bond.

  2. High molecular weight polysaccharide that binds and inhibits virus

    DOE Patents [OSTI]

    Konowalchuk, Thomas W

    2014-01-14T23:59:59.000Z

    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.

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

    E-Print Network [OSTI]

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

    2007-08-22T23:59:59.000Z

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

  4. LIST OF SUBJECT AREA -CODES ISCED -(01.0 Agricultural Sciences) 62 Agriculture, forestry and fishery

    E-Print Network [OSTI]

    .4 Photography, Cinematography) 213 Audio-visual techniques and media production (03.5 Design) (Graphic Design

  5. 1 Copyright 2012 by ASME Proceedings of the ASME/ISCE International Symposium on Flexible Automation

    E-Print Network [OSTI]

    Gosavi, Abhijit

    certain environmental benefits in comparison to forklifts driven by lead-acid batteries that are typically). Most modern forklifts are driven by lead-acid batteries that require recharging or swapping, which on material-handling costs and lead times, which are commonly used in measuring the cost

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

    E-Print Network [OSTI]

    Lopez, Jose Ignacio

    1993-01-01T23:59:59.000Z

    . '. 674 478 I 678 I 3877 3877 3578 I 0 0 0 0 a? 875 675 474 35544? + I 0 Il o 6 II . . ! d I I eaa aaa" I 657 ael I 668, . I dade 4dda I 685C 0 II 4- aa 8 65 55 68 aa le 65 85 86 aa 86 ?" 2' I 10 0' 0' 67...

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

    Office of Science (SC) Website

    AFDC Printable Version Share this resource Send a link to EERE: Alternative Fuels Data Center Home Page to someone by E-mail Share EERE: Alternative Fuels Data Center Home Page on Facebook Tweet about EERE: Alternative Fuels Data Center Home Page on Twitter Bookmark EERE: Alternative1 First Use of Energy for All Purposes (Fuel and Nonfuel), 2002; Level:Energy: Grid Integration Redefining What'sis Taking Over OurThe Iron4 Self-Scrubbing:,,ofOpportunitieshighlights/ The

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

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

    AFDC Printable Version Share this resource Send a link to EERE: Alternative Fuels Data Center Home Page to someone by E-mail Share EERE: Alternative Fuels Data Center Home Page on Facebook Tweet about EERE: Alternative Fuels Data Center Home Page on Twitter Bookmark EERE: Alternative1 First Use of Energy for All Purposes (Fuel and Nonfuel), 2002; Level: National5Sales for4,645U.S. DOEThe Bonneville PowerCherries 82981-1cnHigh School footballHydrogen andHypernucleiNORTHWESTOffice of Science

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

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

    AFDC Printable Version Share this resource Send a link to EERE: Alternative Fuels Data Center Home Page to someone by E-mail Share EERE: Alternative Fuels Data Center Home Page on Facebook Tweet about EERE: Alternative Fuels Data Center Home Page on Twitter Bookmark EERE: Alternative1 First Use of Energy for All Purposes (Fuel and Nonfuel), 2002; Level: National5Sales for4,645U.S. DOEThe Bonneville PowerCherries 82981-1cnHigh School footballHydrogen andHypernucleiNORTHWESTOffice ofOffice of

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

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

    AFDC Printable Version Share this resource Send a link to EERE: Alternative Fuels Data Center Home Page to someone by E-mail Share EERE: Alternative Fuels Data Center Home Page on Facebook Tweet about EERE: Alternative Fuels Data Center Home Page on Twitter Bookmark EERE: Alternative1 First Use of Energy for All Purposes (Fuel and Nonfuel), 2002; Level: National5Sales for4,645U.S. DOEThe Bonneville PowerCherries 82981-1cnHigh School footballHydrogen andHypernucleiNORTHWESTOffice ofOffice The

  11. Deciphering the Effect of Nemaline-Myopathy Nebulin Mutations on Desmin Binding

    E-Print Network [OSTI]

    Jacobs, Krystyna M

    2012-07-11T23:59:59.000Z

    that desmin?s coil 2b binds as well to WT nebulin M160-164 to L5646A nebulin M160-164. ELISA assays were used to determine and compare the binding affinities (Kd) for the each of the nebulin fragments. Through ELISA assays we determined that the binding... nebulin M160-164 protein. The affinity constants (Kds) determined in experiment shown in Figure 6 are 10-fold different between the two samples. In particular, the lower Kd obtained for coil 2B binding to WT nebulin M160-164 suggests a stronger binding...

  12. A familial {open_quotes}balanced{close_quotes} 3;9 translocation with cryptic 8q insertion leading to deletion and duplication of 9p23 loci in siblings

    SciTech Connect (OSTI)

    Wagstaff, J.; Hemann, M. [Children`s Hospital and Harvard Medical School, Boston, MA (United States)

    1994-09-01T23:59:59.000Z

    Families in which a balanced translocation has been transmitted from a normal parent to a child with a phenotypic abnormality have been a longstanding puzzle for human geneticists. A child with phenotypic features of the 9p- syndrome, including metopic craniosynostosis, small ears, abdominal wall defect, and mental retardation, was found to have a cytogenetically balanced 3;9 translocation, with breakpoints at 3p11 and 9p23, inherited from his normal father. He also exhibited marked hypopigmentation of hair and skin. Analysis with a cDNA probe from the TYRP1 (tyrosinase-related protein 1) gene in 9p23 showed heterozygous deletion in the child but in neither parent. This submicroscopic deletion also included loci D9S157, D9S274, D9S268, and D9S267. FISH analysis of the proband`s father indicated the 9p23 loci deleted in his son were present on neither the der(3) nor the der(9) translocation product, but had been inserted into the long arm of chromosome 8. Therefore, the apparent deletion of these loci in the proband was the result of meiotic segregation of the father`s 3;9 translocation chromosomes together with his normal chromosome 8. Neither the deletion from the translocation chromosomes nor the insertion into 8q was detectable by standard chromosome banding techniques. The proband`s sister exhibited speech delay, mild facial dysmorphism, and renal malformation, and her karyotype was 46,XX. Molecular analysis of this sister showed 3 copies of 9p23 sequences, indicating that she had inherited normal chromosomes 3 and 9 from her father as well as the chromosome 8 with the insertion from 9p23. This analysis illustrates a new mechanism to explain cases of phenotypic discordance in familial balanced translocations: submicroscopic deletion of material from the translocation breakpoint and insertion into a third chromosome in the balanced parent, with meiotic segregation leading to loss of the inserted material in the child.

  13. Functional clonal deletion versus suppressor cell-induced transplantation tolerance in chimeras prepared with a short course of total-lymphoid irradiation

    SciTech Connect (OSTI)

    Slavin, S.; Morecki, S.; Weigensberg, M.; Bar, S.; Weiss, L.

    1986-06-01T23:59:59.000Z

    Allogeneic bone marrow (BM) chimeras induced by infusion of BM cells into recipients conditioned with total lymphoid irradiation (TLI) were shown to develop humoral and cell-mediated tolerance to host and donor-type alloantigens by a number of in vitro and in vivo assays. Spleen cells of tolerant chimeras exhibited suppressive activity of mixed lymphocyte reaction (MLR). MLR suppression was not abrogated by depletion of Lyt-2 cells, and neither could Lyt-2-positive cells sorted from the spleens of tolerant chimeras suppress MLR or attenuate graft-versus-host reactivity in vivo. Likewise, specifically unresponsive spleen cells obtained from chimeras could not be induced to respond in MLR against tolerizing host-type cells following depletion of Lyt-2 or passage through a nylon-wool column. Tolerance of chimera spleen cells to host alloantigens, best documented by permanent survival of donor-type skin allografts, could be adoptively transferred into syngeneic recipients treated by heavy irradiation but not into untreated or mildly irradiated recipients. Adoptive transfer of tolerance seemed to be associated with experimental conditions favoring engraftment of tolerant cells rather than suppression of host reactivity. We speculate that although host and/or donor-derived suppressor cells may be operating in reducing the pool of specific alloreactive clones by blocking cell proliferation in response to allogeneic challenge, the final outcome in tolerant chimeras is actual or functional deletion of alloreactive clones.

  14. Mechanism of Ubiquinol Oxidation by the bc1 Complex: Different Domains of the Quinol Binding Pocket and Their Role in the Mechanism and Binding of Inhibitors

    E-Print Network [OSTI]

    Crofts, Antony R.

    electron-transfer systems, occurring ubiquitously in respiratory and photosynthetic chains of mitochondriaMechanism of Ubiquinol Oxidation by the bc1 Complex: Different Domains of the Quinol Binding Pocket and Their Role in the Mechanism and Binding of Inhibitors Antony R. Crofts,*, Blanca Barquera, Robert B. Gennis

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

    E-Print Network [OSTI]

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

    1998-01-01T23:59:59.000Z

    measurements. In Sec. PRB 580163-1829/98/58~23!/15340~4!/$15.00 a tight-binding Hamiltonian , and R. E. Allen , College Station, Texas 77843 June 1998! g Hamiltonian to include interaction with a time- l expression for the second-order susceptibility... potential A; however, the term that is neglected ~involving PRB 58 BRIEF REPORT A2) does not give rise to electronic transitions in the long- wavelength approximation, since it can be eliminated through a unitary transformation.15 Only the last term...

  16. 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)

    2011-09-20T23:59:59.000Z

    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.

  17. Functionalized polymers for binding to solutes in aqueous solutions

    DOE Patents [OSTI]

    Smith, Barbara F.; Robison, Thomas W.

    2006-11-21T23:59:59.000Z

    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

  18. Characterization of Selective Binding of Alkali Cations with Carboxylate

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

    AFDC Printable Version Share this resource Send a link to EERE: Alternative Fuels Data Center Home Page to someone by E-mail Share EERE: Alternative Fuels Data Center Home Page on Facebook Tweet about EERE: Alternative Fuels Data Center Home Page on Twitter Bookmark EERE: Alternative1 First Use of Energy for All Purposes (Fuel and Nonfuel), 2002; Level: National5Sales for4,645 3,625govInstrumentstdmadapInactiveVisiting the TWPSuccessAlamosCharacterization of Selective Binding of Alkali Cations

  19. DNA-Binding Mechanism in Prokaryotic Partition Complex Formation

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

    AFDC Printable Version Share this resource Send a link to EERE: Alternative Fuels Data Center Home Page to someone by E-mail Share EERE: Alternative Fuels Data Center Home Page on Facebook Tweet about EERE: Alternative Fuels Data Center Home Page on Twitter Bookmark EERE: Alternative1 First Use of Energy for All Purposes (Fuel and Nonfuel), 2002; Level: National5Sales for4,645U.S. DOEThe Bonneville Power Administration wouldDECOMPOSITION OF CALCIUM SULFATE: A REVIEWThis rcportJ itDNA-Binding

  20. Pharmacological specificity of some psychotomimetic and antipsychotic agents for the sigma and PCP binding sites

    SciTech Connect (OSTI)

    Itzhak, Y.

    1988-01-01T23:59:59.000Z

    The pharmacological specificity of representative psychotomimetic agents such a phencyclidine (PCP) analogs, opiate benzomorphans and several antipsychotic agents was assessed for the sigma and PCP binding sites. In a series of binding experiments, in rat brain membranes, sigma and PCP binding sites were labeled with (/sup 3/H)-1-(1-(3-hydroxyphenyl) cyclohexyl) piperidine ((/sup 3/H)PCP-3-OH), (+)(/sup 3/H)-N-allylnormetazocine ((+)(/sup 3/H)SKF 10047) and (+) (/sup 3/H)-3-(3-hydroxy-phenyl)-N-(1-propyl) piperidine and ((+)(/sup 3/H)-3-PPP). PCP analogs inhibit potently high affinity (/sup 3/H)PCP-3-OH binding and (+)(/sup 3/H)SKF 10047 binding, moderately the low affinity binding component of (/sup 3/H)PCP-3-OH and very weakly (+) (/sup 3/H)-3-PPP binding. (+)SKF 10047 and cyclazocine are potent to moderate inhibitors of (+)(/sup 3/H)SKF 10047, high affinity (/sup 3/H)PCP-3-OH and (+)(/sup 3/H)-3-PCP-3-OH binding. The antipsychotic agents display high affinity for (+)(/sup 3/H)-3-PPP binding sites, moderate affinity for (+)(/sup 3/H)SKF 10047 sites and have no effect on either the high or low affinity (/sup 3/H)PCP-3-OH binding. 20 references, 3 figures, 2 tables.

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

    E-Print Network [OSTI]

    T. Niksic; D. Vretenar; P. Ring

    2008-09-08T23:59:59.000Z

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

  2. Binding and structure of tetramers in the scaling limit

    E-Print Network [OSTI]

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

    2011-01-01T23:59:59.000Z

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

  3. Binding and structure of tetramers in the scaling limit

    E-Print Network [OSTI]

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

    2012-01-17T23:59:59.000Z

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

  4. Identification of protein binding sites in the promoter regions of a light-responsive gene family in a cyanobacterium

    E-Print Network [OSTI]

    Mueller, Ulrich Wolfgang

    1991-01-01T23:59:59.000Z

    binding sites were characterized that display some interdependence for protein binding ability. One binding site was identified as the primary sequence required for protein binding to the second site. Mutations were introduced into the first binding...lment of the requirements for the degree of MASTER OF SCIENCE December 1991 Major Subject: Biology ZDIBlTZPZCATION OP PROTEIN BINDINQ SITES IN TEB PROMOTER REGIONS OP A LIGHT RESPONSIVE SBBB FAMILY IN A CYANOBACTBRZUM A Thesis by ULRICH WOLFGANG...

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

    E-Print Network [OSTI]

    Kagan, Yonatan Savir Jacob

    2015-01-01T23:59:59.000Z

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

  6. Autoradiographic localization of endothelin-1 binding sites in the cardiovascular and respiratory systems

    SciTech Connect (OSTI)

    Power, R.F.; Wharton, J.; Zhao, Y.; Bloom, S.R.; Polak, J.M.

    1989-01-01T23:59:59.000Z

    Specific high-affinity binding sites for endothelin-1 (ET-1) have been demonstrated in peripheral tissues using the technique of in vitro receptor autoradiography. Binding was time dependent and saturable and inhibited by coincubation with an excess of unlabeled ET-1 but resistant to dissociation. Binding sites were localized to blood vessels of all sizes including coronary arteries, intrapulmonary vessels, and intrarenal and intrasplenic arteries. In addition, high-affinity binding sites were identified on airway smooth muscle, over alveolar septa, and on nerve trunks. Scatchard analysis of the data revealed a Bmax of 250 amol/mm2 and a Kd of 0.1 nM for the binding of rat tracheal smooth muscle, with similar values for porcine coronary artery. The localization of binding sites is consistent with the known effects of ET-1 and suggests a direct action on specific receptors.

  7. The effects of temperature on thyroid hormone binding to serum proteins in sea turtles

    E-Print Network [OSTI]

    Haynes, Shane Patrick

    1990-01-01T23:59:59.000Z

    . S. , Texas AKN University Chair of Advisory Committee: Dr. Duncan S. HacKenzie The high affinity binding of thyroid hormones to plasma proteins is a critical step in their peripheral delivery. This study was undertaken to investigate whether... changes in temperature might alter thyroid hormone binding to plasma binding proteins in poikilotherms. The objectives were to determine if high affinity thyroid hormo plasma hi ding proteins e ist i the green (ghelo ia %dash, ioggerhead tata caretta...

  8. E-Print Network 3.0 - a-binding protein acbp6 Sample Search Results

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

    Biology and Medicine 3 Femtomole Mixer for Microsecond Kinetic Studies of Protein Folding Summary: kinetics using FRET with acyl-CoA binding protein. In protein folding,...

  9. Anthraquinone Photonuclease Structure Determines Its Mode of Binding to DNA and the Cleavage

    E-Print Network [OSTI]

    Williams, Loren

    Anthraquinone Photonuclease Structure Determines Its Mode of Binding to DNA and the Cleavage recently described a set of anthraquinone derivatives that act as photonucleases.6 Three classes

  10. 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).

  11. Prediction of the binding affinities of peptides to class II MHC using a ...

    E-Print Network [OSTI]

    andrew

    2010-01-18T23:59:59.000Z

    Characteristic properties of peptide binding to class II MHC molecules can be inferred from ... conserved hydrogen bonds with the MHC [2]. Peptide side chains

  12. active-site structure binding: Topics by E-print Network

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

    Threshold Occupancy and Specific Cation Binding Modes in the Hammerhead Ribozyme Active Site components to facilitate catalysis through electrostatic engineering. In the case of...

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

    E-Print Network [OSTI]

    Tian, Guoxin

    2013-01-01T23:59:59.000Z

    Sequestering uranium from seawater: binding strength andin sequestering uranium from seawater, forms strongExtraction of uranium from seawater is very challenging, not

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

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

    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...

  15. Comparison of crystal and solution hemoglobin binding of selected antigelling agents and allosteric modifiers

    SciTech Connect (OSTI)

    Mehanna, A.S.; Abraham, D.J. (Virginia Commonwealth Univ., Richmond (USA))

    1990-04-24T23:59:59.000Z

    This paper details comprehensive binding studies (solution and X-ray) of human hemoglobin A with a group of halogenated carboxylic acids that were investigated as potential antisickling agents. It is, to our knowledge, the first study to compare solution and crystal binding for a series of compounds under similar high-salt conditions used for cocrystallization. The compounds include ((3,4-dichlorobenzyl)oxy)acetic acid, ((p-bromobenzyl)oxy)acetic acid, clofibric acid, and bezafibrate. The location and stereochemistry of binding sites have been established by X-ray crystallography, while the number of binding sites and affinity constants were measured by using equilibrium dialysis. The observed crystal structures are consistent with the binding observed in solution and that the number of binding sites is independent of salt concentration, while the binding constant increases with increasing salt concentration. The studies also reveal that relatively small changes in the chemical structure of a drug molecule can result in entirely different binding sites on the protein. Moreover, the X-ray studies provide a possible explanation for the multiplicity in function exhibited by these compounds as allosteric modulators and/or antisickling agents. Finally, the studies indicate that these compounds bind differently to the R and T states of hemoglobin, and observation of special significance to the original design of these agents.

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

    E-Print Network [OSTI]

    Gustavo R. Gonzalez-Martin

    2008-05-03T23:59:59.000Z

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

  17. atp-binding rna aptamer: Topics by E-print Network

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

    the b-phosphate. Induced-fit therefore strengthens active; ATP-binding site; induced fit; free energy transduction; ground-state destabilization Yin, Y. Whitney 3 Mutant...

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

    E-Print Network [OSTI]

    Cho, Samuel Sung-Il

    2007-01-01T23:59:59.000Z

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

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

    E-Print Network [OSTI]

    I. Casinos

    2008-05-22T23:59:59.000Z

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

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

    SciTech Connect (OSTI)

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

    2014-06-01T23:59:59.000Z

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

  1. Molecular modeling study on the effect of residues distant from the nucleotide-binding portion on RNA binding in Staphylococcus aureus Hfq

    E-Print Network [OSTI]

    Lee, Keun Woo

    of Quality of Life, Korea Research Institute of Standards and Science, Daejeon 305-340, Republic of Korea c region of the hexamer, and binds in a circular manner except for Journal of Molecular Graphics

  2. 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)

    2014-05-07T23:59:59.000Z

    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.

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

    E-Print Network [OSTI]

    Hartemink, Alexander

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

  4. Chemical binding energies of point defects in palladium doped with hydrogen and d impurities

    E-Print Network [OSTI]

    Paris-Sud XI, Université de

    1001 Chemical binding energies of point defects in palladium doped with hydrogen and d impurities C calculate the chemical binding energy of a pair of hydrogen atoms in palladium within the infinite dilution] it is often assumed that the dominant contribution to the interaction energy between hydrogen atoms

  5. Measuring molecular rupture forces between single actin filaments and actin-binding proteins

    E-Print Network [OSTI]

    Kamm, Roger D.

    Measuring molecular rupture forces between single actin filaments and actin-binding proteins Jorge, and accepted by the Editorial Board April 24, 2008 (received for review June 29, 2007) Actin-binding proteins to model the mechanical properties of actin networks grown in vitro; however, there is a lack

  6. Direct calculation of the binding free energies of FKBP ligands Hideaki Fujitani,a

    E-Print Network [OSTI]

    Snow, Christopher

    Direct calculation of the binding free energies of FKBP ligands Hideaki Fujitani,a Yoshiaki Tanida energies of binding for eight ligands to FKBP protein were performed using the Fujitsu BioServer massively parallel computer. Using the latest version of the general assisted model building with energy refinement

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

    E-Print Network [OSTI]

    Hinow, Peter

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

  8. Binding and Translocation of Termination Factor Rho Studied at the Single-Molecule Level

    E-Print Network [OSTI]

    Straight, Aaron

    Binding and Translocation of Termination Factor Rho Studied at the Single-Molecule Level Daniel J; force spectroscopy Rho termination factor is an essential hexameric helicase responsible for terminating to investigate RhoRNA binding in- teractions at the Rho utilization site of the tR1 terminator. Our results

  9. Gonadotropin binding sites in eel ovary : Autoradiographic visualization and new data on specificity

    E-Print Network [OSTI]

    Paris-Sud XI, Universit de

    chorionic gonadotropin (hCG) binding was also observed consis- tently. Earlier data on the stimulation of in vitro cyclic AMP (cAMP) production by eel ovary led us to hypothesize that several types of GTH this hypothesis. The effects of an in vivo carp pituitary treatment on in vitro binding were also considered

  10. ON THE THERMODYNAMICS AND KINETICS OF THE COOPERATIVE BINDING OF BACTERIOPHAGE T4-

    E-Print Network [OSTI]

    Kowalczykowski, Stephen C.

    ON THE THERMODYNAMICS AND KINETICS OF THE COOPERATIVE BINDING OF BACTERIOPHAGE T4- CODED GENE 32 of thermodynamic, and preliminary kinetic, studies on the molecular details and specificity of interaction of phage into the molecular origins of binding cooperativity is obtained by determining these thermodynamic parameters also

  11. affinity brain membrane-binding: Topics by E-print Network

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

    affinity brain membrane-binding First Page Previous Page 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 Next Page Last Page Topic Index 1 Membrane Binding of...

  12. A Novel Dimerization Interface of Cyclic Nucleotide Binding Domain, which is

    E-Print Network [OSTI]

    Paris-Sud XI, Université de

    1 A Novel Dimerization Interface of Cyclic Nucleotide Binding Domain, which is Disrupted Modeling 18, 9 (2012) 4053-4060" DOI : 10.1007/s00894-012-1404-5 #12;2 ABSTRACT Cyclic nucleotide binding and eukaryota. CNBD activation by cyclic nucleotide monophosphate (cNMP) is studied well in case of several

  13. Geometric Binding Site Design for Surface-Tension Driven Self-Assembly

    E-Print Network [OSTI]

    Geometric Binding Site Design for Surface-Tension Driven Self-Assembly Xiaorong Xiong, Sheng 98195-2500 Email: xrxiong@u.washington.edu Abstract-- Surface-tension driven self-assembly techniques-assembly, micro assembly, MEMS, hy- drophobic, hydrophilic, surface energy, surface tension force, binding site

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

    E-Print Network [OSTI]

    Roberto Chignola; Alessio Del Fabbro; Edoardo Milotti

    2009-09-10T23:59:59.000Z

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

  15. A model study of cooperative binding of ionic surfactants to oppositely charged flexible polyions

    E-Print Network [OSTI]

    T. Nishio; T. Shimizu; Sh. Yoshida; A. Minakata

    2015-01-10T23:59:59.000Z

    A novel statistical model for the cooperative binding of monomeric ligands to a linear lattice is developed to study the interaction of ionic surfactant molecules with flexible polyion chain in dilute solution. Electrostatic binding of a ligand to a site on the polyion and hydrophobic associations between the neighboring bound ligands are assumed to be stochastic processes. Ligand association separated by several lattice points within defined width is introduced for the flexible polyion. Model calculations by the Monte Carlo method are carried out to investigate the binding behavior. The hypothesis on the ligand association and its width on the chain are of importance in determining critical aggregation concentration and binding isotherm. The results are reasonable for the interpretations of several surfactant-flexible polyion binding experiments. The implications of the approach are presented and discussed.

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

    SciTech Connect (OSTI)

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

    2011-12-31T23:59:59.000Z

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

  17. Binding Energy and the Fundamental Plane of Globular Clusters

    E-Print Network [OSTI]

    Dean E. McLaughlin

    2000-02-03T23:59:59.000Z

    A physical description of the fundamental plane of Galactic globular clusters is developed which explains all empirical trends and correlations in a large number of cluster observables and provides a small but complete set of truly independent constraints on theories of cluster formation and evolution in the Milky Way. Within the theoretical framework of single-mass, isotropic King models, it is shown that (1) 39 regular (non--core-collapsed) globulars with measured core velocity dispersions share a common V-band mass-to-light ratio of 1.45 +/- 0.10, and (2) a complete sample of 109 regular globulars reveals a very strong correlation between cluster binding energy and total luminosity, regulated by Galactocentric position: E_b \\propto (L^{2.05} r_{\\rm gc}^{-0.4}). The observational scatter about either of these two constraints can be attributed fully to random measurement errors, making them the defining equations of a fundamental plane for globular clusters. A third, weaker correlation, between total luminosity and the King-model concentration parameter, c, is then related to the (non-random) distribution of globulars on the plane. The equations of the FP are used to derive expressions for any cluster observable in terms of only L, r_{\\rm gc}, and c. Results are obtained for generic King models and applied specifically to the globular cluster system of the Milky Way.

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

    SciTech Connect (OSTI)

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

    2013-09-25T23:59:59.000Z

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

  19. End-to-End Support for QoS-Aware Service Selection, Binding and Mediation in VRESCo

    E-Print Network [OSTI]

    Dustdar, Schahram

    to them (see Figure 1b). Service Contract Service Registry Service Provider Service Consumer Bind/Execute PublishFind (a) SOA Model Service Contract Service Provider Service Consumer Bind/Execute (b) SOA Practice

  20. Dynamic Nuclear Polarization Study of Inhibitor Binding to the M2[subscript 1860] Proton Transporter from Influenza A

    E-Print Network [OSTI]

    Andreas, Loren B.

    We demonstrate the use of dynamic nuclear polarization (DNP) to elucidate ligand binding to a membrane protein using dipolar recoupling magic angle spinning (MAS) NMR. In particular, we detect drug binding in the proton ...

  1. THE JOURNAL OF CHEMICAL PHYSICS 134, 134701 (2011) Binding of hydrogen on benzene, coronene, and graphene from quantum

    E-Print Network [OSTI]

    Alf, Dario

    2011-01-01T23:59:59.000Z

    THE JOURNAL OF CHEMICAL PHYSICS 134, 134701 (2011) Binding of hydrogen on benzene, coronene the binding energy curves of hydrogen on benzene, coronene, and graphene. The DMC results on benzene agree

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

    E-Print Network [OSTI]

    Li, Fang

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

  3. Acidic C-terminal tail of the ssDNA-binding protein of bacteriophage T7 and ssDNA

    E-Print Network [OSTI]

    Richardson, Charles C.

    Acidic C-terminal tail of the ssDNA-binding protein of bacteriophage T7 and ssDNA compete. Prokaryotic ssDNA-binding proteins share a conserved DNA-binding fold and an acidic C-terminal tail. It has been proposed that in the absence of ssDNA, the C-terminal tail contacts the ssDNA-binding cleft

  4. Homotypic clusters of transcription factor binding sites: a model system for understanding the physical mechanics of gene expression

    E-Print Network [OSTI]

    Ezer, Daphne; Zabet, Nicolae Radu; Adryan, Boris

    2014-08-01T23:59:59.000Z

    for studying complex CREs Recently, it has become possible to synthesize thousands of pro- moters or enhancers, and tomeasure the resulting level of gene expres- sion in parallel, an experimental design known as a massively parallel gene expression assay [9... heterotypic clusters influence gene expression. As the number of adjacent TF binding sites increases, the number of possible permutations of binding sites expands at a factorial scale. The distance between the binding sites and the order of the binding sites...

  5. Ropizine concurrently enhances and inhibits ( sup 3 H) dextromethorpan binding to different structures of the guinea pig brain: Autoradiographic evidence for multiple binding sites

    SciTech Connect (OSTI)

    Canoll, P.D.; Smith, P.R.; and Musacchio, J.M. (N.Y.U. Medical Center, New York (USA))

    1990-01-01T23:59:59.000Z

    Ropizine produces a simultaneous enhancement and inhibition of ({sup 3}H) dextromethorphan (DM) high-affinity binding to different areas of the guinea pig brain. These results imply that there are two distinct types of high-affinity ({sup 3}H)DM binding sites, which are present in variable proportions in different brain structures. The ropizine-enhances ({sup 3}H)DM binding type was preferentially inhibited by (+)-pentazocine. This is consistent with the presumption that the (+)-pentazocine-sensitive site is identical with the common site for DM and 3-(-3-Hydroxphenyl)-N-(1-propyl)piperidine ((+)-3-PPP). The second binding type, which is inhibited by ropizine and is not so sensitive to (+){minus} pentazocine, has not been fully characterized. This study demonstrates that the biphasic effects to ropizine are due, at least in part, to the effects of ropizine on two different types of ({sup 3}H)DM binding sites. However, this study does not rule out that the common DM/(+)-3-PPP site also might be inhibited by higher concentrations of ropizine.

  6. Receptor binding characteristics of tritiated misoprostol free acid in enriched canine parietal cells

    SciTech Connect (OSTI)

    Tsai, B.S.; Kessler, L.K.; Conway, R.G.; Schoenhard, G.; Stolzenbach, J.; Collins, P.; Kramer, S.; Butchko, G.M.; Bauer, R.F.

    1986-03-01T23:59:59.000Z

    Misoprostol (MISO) is a synthetic prostaglandin (PG) E/sub 1/ methyl ester with gastric antisecretory and mucosal protective properties. MISO is rapidly de-esterified to misoprostol free acid (MISO-FA) in enriched (65-80%) canine parietal cell preparations. Both forms appear to possess equivalent antisecretory potency and (/sup 3/H) MISO-FA is stable in these preparations. (/sup 3/H) MISO-FA binding was reversible and saturable with a maximal number of binding sites estimated at 8138 +/- 1893 per cell. The scatchard plot was linear, indicating a single, high affinity receptor population with a dissociation constant of 11 +/- 2.6 x 10/sup -9/ M. Unlabeled MISO-FA and MISO were equally potent inhibitors (IC/sub 50/, approx. 10/sup -8/M) of (/sup 3/H) MISO-FA binding. At 10/sup -5/ M, the dinor and tetranor ..beta..-oxidation metabolites of MISO were weak binding inhibitors. Strict stereospecific binding was shown by MISO stereoisomers, and the 11R, 16S isomer was most active. Both PGE/sub 1/ and 16,16 dimethyl PGE/sub 2/ were potent binding inhibitors, but PGF/sub 1/..cap alpha.. (10/sup -6/ M) and Hoe 892 (10/sup -5/ M), a stable PGI/sub 2/ analog, were weak inhibitors. Neither histamine or cimetidine competed for binding sites. These data indicate the presence of stereospecific E-type prostaglandin receptors in enriched canine parietal cell preparations.

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

    SciTech Connect (OSTI)

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

    1996-05-01T23:59:59.000Z

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

  8. Putative Zinc Finger Protein Binding Sites Are Over-Represented in the Boundaries of Methylation-Resistant

    E-Print Network [OSTI]

    Putative Zinc Finger Protein Binding Sites Are Over- Represented in the Boundaries of Methylation that there are several over-represented putative Transcription Factor Binding Sites (TFBSs) in methylation-resistant CpG islands, and a specific group of zinc finger protein binding sites are over-represented in boundary

  9. Biochemistry 1994, 33, 13977-13988 13977 Effect of Conformational Flexibility and Solvation on Receptor-Ligand Binding

    E-Print Network [OSTI]

    Vajda, Sandor

    on Receptor-Ligand Binding Free Energies+ Sandor Vajda, Zhiping Weng, Rakefet Rosenfeld, and Charles De is presented for determing the free energy change accompanying ligand binding to protein receptors. The most conformational change on binding, to the free energy. Flexibility introduces two additional terms in the free

  10. Biochemistry 1994,33, 14565-14578 14565 Kinetic Mechanism of Adenine Nucleotide Binding to and Hydrolysis by the

    E-Print Network [OSTI]

    Lohman, Timothy M.

    Biochemistry 1994,33, 14565-14578 14565 Kinetic Mechanism of Adenine Nucleotide Binding nucleotides, we have investigated the kinetic mechanism of adenine nucleotide binding to the Rep monomer not significantly change the intrinsic tryptophan fluorescence, the binding of the fluorescent nucleotide analogue

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

    E-Print Network [OSTI]

    Lohman, Timothy M.

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

  12. GABA{sub A} receptor open-state conformation determines non-competitive antagonist binding

    SciTech Connect (OSTI)

    Chen Ligong [Environmental Chemistry and Toxicology Laboratory, Department of Environmental Science, Policy and Management, University of California, Berkeley, CA 94720 (United States); Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA 94158 (United States); Xue Ling [Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720 (United States); Giacomini, Kathleen M. [Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA 94158 (United States); Casida, John E., E-mail: ectl@berkeley.edu [Environmental Chemistry and Toxicology Laboratory, Department of Environmental Science, Policy and Management, University of California, Berkeley, CA 94720 (United States)

    2011-02-01T23:59:59.000Z

    The {gamma}-aminobutyric acid (GABA) type A receptor (GABA{sub A}R) is one of the most important targets for insecticide action. The human recombinant {beta}3 homomer is the best available model for this binding site and 4-n-[{sup 3}H]propyl-4'-ethynylbicycloorthobenzoate ([{sup 3}H]EBOB) is the preferred non-competitive antagonist (NCA) radioligand. The uniquely high sensitivity of the {beta}3 homomer relative to the much-less-active but structurally very-similar {beta}1 homomer provides an ideal comparison to elucidate structural and functional features important for NCA binding. The {beta}1 and {beta}3 subunits were compared using chimeragenesis and mutagenesis and various combinations with the {alpha}1 subunit and modulators. Chimera {beta}3/{beta}1 with the {beta}3 subunit extracellular domain and the {beta}1 subunit transmembrane helices retained the high [{sup 3}H]EBOB binding level of the {beta}3 homomer while chimera {beta}1/{beta}3 with the {beta}1 subunit extracellular domain and the {beta}3 subunit transmembrane helices had low binding activity similar to the {beta}1 homomer. GABA at 3 {mu}M stimulated heteromers {alpha}1{beta}1 and {alpha}1{beta}3 binding levels more than 2-fold by increasing the open probability of the channel. Addition of the {alpha}1 subunit rescued the inactive {beta}1/{beta}3 chimera close to wildtype {alpha}1{beta}1 activity. EBOB binding was significantly altered by mutations {beta}1S15'N and {beta}3N15'S compared with wildtype {beta}1 and {beta}3, respectively. However, the binding activity of {alpha}1{beta}1S15'N was insensitive to GABA and {alpha}1{beta}3N15'S was stimulated much less than wildtype {alpha}1{beta}3 by GABA. The inhibitory effect of etomidate on NCA binding was reduced more than 5-fold by the mutation {beta}3N15'S. Therefore, the NCA binding site is tightly regulated by the open-state conformation that largely determines GABA{sub A} receptor sensitivity. - Graphical Abstract: Display Omitted Research Highlights: > The {beta}1 and {beta}3 subunits were compared by chimeragenesis, mutagenesis and modulators. > Low {beta}1 NCA binding was rescued by replacing its transmembrane helices with those of {beta}3. > GABA at 3 {mu}M stimulated heteromers {alpha}1{beta}1 and {alpha}1{beta}3 binding levels more than 2-fold. > Mutation at 15' position in TM2 reduced GABA stimulation of NCA binding. > The open-state conformation largely determines GABAA receptor sensitivity to NCAs.

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

    DOE Patents [OSTI]

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

    2010-12-28T23:59:59.000Z

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

  14. New binding materials for metal hydride electrodes which permit good recyclability

    SciTech Connect (OSTI)

    Hara, T.; Yasuda, N. (Japan Synthetic Rubber Co., Ltd., Yokkaichi (Japan). Development Center); Takeuchi, Y. (Japan Synthetic Rubber Co., Ltd., Tokyo (Japan). Electronics Project Dept.); Sakai, T.; Uchiyama, A.; Miyamura, H.; Kuriyama, N.; Ishikawa, H. (Government Industrial Research Inst., Osaka (Japan))

    1993-09-01T23:59:59.000Z

    Thermoplastic elastomers such as styrene-butadiene-styrene block copolymer (SBS) and styrene-ethylene/butylene-styrene block copolymer (SEBS) were used successfully as binding materials for metal hydride (MH) electrodes of a nickel-metal hydride battery. These binding materials have a rubber-like nature and are soluble in organic solvents. It was easy to remove the alloy powder from a used electrode for recycling. The battery performance depended on both the kind and amount of binding materials. The best discharge capacity and rate capability were obtained for MH electrodes containing 2--5 weight percent (w/o) SEBS. The particle size distributions for the alloy were examined successfully.

  15. FOXM1 binds directly to non-consensus sequences in the human genome

    E-Print Network [OSTI]

    Sanders, Deborah A.; Gormally, Michael V.; Marsico, Giovanni; Beraldi, Dario; Tannahill, David; Balasubramanian, Shankar

    2015-06-23T23:59:59.000Z

    , Addenbrookes Hospital, Hills Road, Cambridge CB2 0SP, UK 4 Present address: Domainex, 162 Cambridge Science Park, Milton Road, Cambridge CB4 0GH, UK Abstract Background The Forkhead (FKH) transcription factor FOXM1 is a key regulator of the cell cycle... . Additionally, some transcription factors show different modes of recruitment to chromatin at specific sub-sets of genomic binding sites. For example, the ETS family member ELK1 [23] has two distinct types of binding modes, either binding redundantly...

  16. Partial proteolytic digestion of the mammary prolactin receptor: Identification of smaller prolactin binding fragments

    SciTech Connect (OSTI)

    Dusanter-Fourt, I.; Kelly, P.A.; Djiane, J. (Institut National de la Recherche Agronomique, Jouy-en-Josas (France))

    1990-01-01T23:59:59.000Z

    Partial proteolytic digestion of the mammary prolactin (PRL) receptor was used to generate receptor fragments and analyze their immunoreactivity and PRL binding properties. Tryptic digestion of the PRL receptor produced two immunoreactive fragments (Mr approximately 30,000 and approximately 15,000) that reacted with a monoclonal anti-PRL receptor antibody and still specifically bound PRL, while the complete immunoreactive PRL binding unit (Mr approximately 42,000) disappeared. Neither chymotrypsin nor V8 protease were able to generate any immunoreactive receptor fragments. These receptor fragments may represent smaller PRL binding receptor form(s) of biological significance.

  17. Systematic analysis of the role of RNA-binding proteins in the regulation of RNA stability

    E-Print Network [OSTI]

    Hasan, Ayesha; Cotobal, Cristina; Duncan, Caia D. S.; Mata, Juan

    2014-11-06T23:59:59.000Z

    -MTAB-2709 (RIp-chip experiments) and RNA-seq of splicing mutants (E-MTAB-2695). Funding: This work was supported by a Biotechnology and Biological Sciences Research Council grant BB/J007153/1 to JM (http://www.bbsrc.ac.uk), a Masdar Institute fellowship... developmental or environmental situations. For example, we have previously shown that the RBP Meu5 regulates mRNA stability during meiosis [12]. In vegetative cells, however, Meu5 is not expressed, and deletion of meu5 did not cause any changes...

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

    E-Print Network [OSTI]

    Jayaraman, Akila

    2011-01-01T23:59:59.000Z

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

  19. Identification of Novel Small Molecule Inhibitors of Core-Binding Factor Dimerization by Computational

    E-Print Network [OSTI]

    Lilien, Ryan

    of a ligand database into the binding site of the protein. Ligands are then ranked by the number and quality (IIS-9906790, EIA- 0102710, EIA-0102712, EIA-9818299, EIA-9802068, and EIA-0305444). Author's current

  20. Conformational Transitions upon Ligand Binding: Holo-Structure Prediction from Apo Conformations

    E-Print Network [OSTI]

    de Groot, Bert

    Conformational Transitions upon Ligand Binding: Holo- Structure Prediction from Apo Conformations Daniel Seeliger, Bert L. de Groot* Computational Biomolecular Dynamics Group, Max design. Hence, if only an unbound (apo) structure is available distinct from the ligand

  1. Networks of Coupled Rotators: Relationship between Structures and Internal Dynamics in Metal-Binding Proteins.

    E-Print Network [OSTI]

    -Binding Proteins. Applications to apo- and holo-Calbindin Anne Dhulesia, Daniel Abergel,* and Geoffrey Bodenhausen, France Received October 17, 2006; E-mail: daniel.abergel@ens.fr Abstract: This article presents

  2. Dynamical bond cooperativity enables very fast and strong binding between sliding surfaces

    E-Print Network [OSTI]

    Trmborg, Jrgen Kjoshagen

    2015-01-01T23:59:59.000Z

    Cooperative binding affects many processes in biology, but it is commonly addressed only in equilibrium. In this work we explore dynamical cooperativity in driven systems, where the cooperation occurs because some of the bonds change the dynamical response of the system to a regime where the other bonds become active. To investigate such cooperativity we study the frictional binding between two flow driven surfaces that interact through a large population of activated bonds. In particular, we study systems where each bond can have two different modes: one mode corresponds to a fast forming yet weak bond, and the other is a strong yet slow forming bond. We find considerable cooperativity between both types of bonds. Under some conditions the system behaves as if there were only one binding mode, corresponding to a strong and fast forming bond. Our results may have important implications on the friction and adhesion between sliding surfaces containing complementary binding motifs, such as in the case of cells b...

  3. Chromosome-Biased Binding and Gene Regulation by the Caenorhabditis elegans DRM Complex

    E-Print Network [OSTI]

    Tabuchi, Tomoko M.

    DRM is a conserved transcription factor complex that includes E2F/DP and pRB family proteins and plays important roles in development and cancer. Here we describe new aspects of DRM binding and function revealed through ...

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

    E-Print Network [OSTI]

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

    2012-06-27T23:59:59.000Z

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

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

    E-Print Network [OSTI]

    Green, David F.

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

  6. Solution Structure of the cGMP Binding GAF Domain fromPhosphodiesteras...

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

    of cGMP through its regulation of cGMP hydrolysis. Hydrolytic activity of the C-terminal catalytic domain is increased by cGMP binding to the N-terminal GAF A domain. We...

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

    E-Print Network [OSTI]

    Spivakov, Mikhail

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

  8. On the electrostatic component of protein-protein binding free energy

    E-Print Network [OSTI]

    Talley, Kemper; Ng, Carmen; Shoppell, Michael; Kundrotas, Petras J.; Alexov, Emil

    2008-11-05T23:59:59.000Z

    of the electrostatic component of binding free energy (DeltaDeltaGel) with respect with different force fields (Charmm, Amber, and OPLS), different values of the internal dielectric constant, and different presentations of molecular surface (different values...

  9. Quantitative estimates on the enhanced binding for the Pauli-Fierz operator

    SciTech Connect (OSTI)

    Barbaroux, Jean-Marie; Linde, Helmut; Vugalter, Semjon [Centre de Physique Theorique, Luminy Case 907, 13288 Marseille Cedex 9 (France); Departement de Mathematiques, Universite du Sud-Toulon-Var, Avenue de l'Universite, 83957 La Garde Cedex (France); Facultad de Fisica, P. Universidad Catolica de Chile, Casilla 306, Santiago 22 (Chile); Mathematisches Institut, Ludwig-Maximilians-Universitaet Muenchen, Theresienstrasse 39, 80333 Munich (Germany); Institut fuer Analysis, Dynamik und Modelierung, Universitaet Stuttgart, Stuttgart (Germany)

    2005-12-15T23:59:59.000Z

    For a quantum particle interacting with a short-range potential, we estimate from below the shift of its binding threshold, which is due to the particle interaction with a quantized radiation field.

  10. 2D IR spectroscopy and computational modeling : application to protein folding and binding

    E-Print Network [OSTI]

    Ganim, Ziad

    2010-01-01T23:59:59.000Z

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

  11. Visualizing KcsA Conformational Changes upon Ion Binding by Infrared Spectroscopy and Atomistic Modeling

    E-Print Network [OSTI]

    Stevenson, Paul

    The effect of ion binding in the selectivity filter of the potassium channel KcsA is investigated by combining amide I Fourier-transform infrared spectroscopy with structure-based spectral modeling. Experimental difference ...

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

    E-Print Network [OSTI]

    Yakamavich, Joseph Andrew

    2008-01-01T23:59:59.000Z

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

  13. Nucleotide Binding and Conformational Switching in the Hexameric Ring of a AAA+ Machine

    E-Print Network [OSTI]

    Stinson, Benjamin Michael

    ClpX, a AAA+ ring homohexamer, uses the energy of ATP binding and hydrolysis to power conformational changes that unfold and translocate target proteins into the ClpP peptidase for degradation. In multiple crystal structures, ...

  14. Structures of Human Pumilio with Noncognate RNAs Reveal Molecular Mechanisms for Binding Promiscuity

    SciTech Connect (OSTI)

    Gupta,Y.; Nair, D.; Wharton, R.; Aggarwal, A.

    2008-01-01T23:59:59.000Z

    Pumilio is a founder member of the evolutionarily conserved Puf family of RNA-binding proteins that control a number of physiological processes in eukaryotes. A structure of human Pumilio (hPum) Puf domain bound to a Drosophila regulatory sequence showed that each Puf repeat recognizes a single nucleotide. Puf domains in general bind promiscuously to a large set of degenerate sequences, but the structural basis for this promiscuity has been unclear. Here, we describe the structures of hPum Puf domain complexed to two noncognate RNAs, CycBreverse and Puf5. In each complex, one of the nucleotides is ejected from the binding surface, in effect, acting as a 'spacer.' The complexes also reveal the plasticity of several Puf repeats, which recognize noncanonical nucleotides. Together, these complexes provide a molecular basis for recognition of degenerate binding sites, which significantly increases the number of mRNAs targeted for regulation by Puf proteins in vivo.

  15. Nucleotide binding and conformational switching in the hexameric ring of a AAA+ machine

    E-Print Network [OSTI]

    Stinson, Benjamin M. (Benjamin Michael)

    2015-01-01T23:59:59.000Z

    ATP-powered proteases enforce protein quality-control and regulation in all domains of life. ClpX, a AAA+ ring homohexamer, uses the energy of ATP binding and hydrolysis to power conformational changes that unfold and ...

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

    E-Print Network [OSTI]

    Todd, Ryan Christopher, 1981-

    2010-01-01T23:59:59.000Z

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

  17. apobec3g binding site: Topics by E-print Network

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

    Ser-142 (14). Ser-129 is believed to be a substrate for glycogen synthase kinase 3 Brownfield, Mark S. 73 Similarity Analysis of Protein Binding Sites: A Generalization of the...

  18. acyl-coa binding protein: Topics by E-print Network

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

    Ser-142 (14). Ser-129 is believed to be a substrate for glycogen synthase kinase 3 Brownfield, Mark S. 131 A High-Throughput Solid-Phase Microplate Protein-Binding Assay to...

  19. ap-2alpha binding site: Topics by E-print Network

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

    Ser-142 (14). Ser-129 is believed to be a substrate for glycogen synthase kinase 3 Brownfield, Mark S. 53 Similarity Analysis of Protein Binding Sites: A Generalization of the...

  20. acyl-coa binding proteins: Topics by E-print Network

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

    Ser-142 (14). Ser-129 is believed to be a substrate for glycogen synthase kinase 3 Brownfield, Mark S. 131 A High-Throughput Solid-Phase Microplate Protein-Binding Assay to...

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

    E-Print Network [OSTI]

    Clark, Amy Eunice

    1997-01-01T23:59:59.000Z

    EFFECTS OF DIETARY FIBER AND CARCINOGEN ON FATTY ACID BINDING PROTEIN EXPRESSION IN EXFOLIATED COLONOCYTES A Thesis by AMY EUNICE CLARK Submitted to the Office of Gmduate Studies of Texas A&M University in partial fulfillment...) Bryan H. Johnson (Head of Department) August 1997 Major Subject: Nutrition ABSTRACT Effects of Dietary Fiber and Carcinogen on Fatty Acid Binding Protein Expression in Exfoliated Colonocytes. (August 1997) Amy Eunice Clark, B. S. , Texas A...

  2. Ab-initio calculation of the ${}^6Li$ binding energy with the Hybrid Multideterminant scheme

    E-Print Network [OSTI]

    Giovanni Puddu

    2010-06-09T23:59:59.000Z

    We perform an ab-initio calculation for the binding energy of ${}^6Li$ using the CD-Bonn 2000 NN potential renormalized with the Lee-Suzuki method. The many-body approach to the problem is the Hybrid Multideterminant method. The results indicate a binding energy of about $31 MeV$, within a few hundreds KeV uncertainty. The center of mass diagnostics are also discussed.

  3. Internal binding sites for MSH: Analyses in wild-type and variant Cloudman melanoma cells

    SciTech Connect (OSTI)

    Orlow, S.J.; Hotchkiss, S.; Pawelek, J.M. (Yale Univ. School of Medicine, New Haven, CT (USA))

    1990-01-01T23:59:59.000Z

    Cloudman S91 mouse melanoma cells express both external (plasma membrane) and internal binding sites for MSH. Using 125I-beta melanotropin (beta-MSH) as a probe, we report here an extensive series of studies on the biological relevance of these internal sites. Cells were swollen in a hypotonic buffer and lysed, and a particulate fraction was prepared by high-speed centrifugation. This fraction was incubated with 125I-beta-MSH with or without excess nonradioactive beta-MSH in the cold for 2 hours. The material was then layered onto a step-wise sucrose gradient and centrifuged; fractions were collected and counted in a gamma counter or assayed for various enzymatic activities. The following points were established: (1) Specific binding sites for MSH were observed sedimenting at an average density of 50% sucrose in amelanotic cells and at higher densities in melanotic cells. (2) These sites were similar in density to those observed when intact cells were labeled externally with 125I-beta-MSH and then warmed to promote internalization of the hormone. (3) Most of the internal binding sites were not as dense as fully melanized melanosomes. (4) In control experiments, the MSH binding sites were not found in cultured hepatoma cells. (5) Variant melanoma cells, which differed from the wild-type in their responses to MSH, had reduced expression of internal binding sites even though their ability to bind MSH to the outer cell surface appeared normal. (MSH-induced responses included changes in tyrosinase, dopa oxidase, and dopachrome conversion factor activities, melanization, proliferation, and morphology.) (6) Isobutylmethylxanthine, which enhanced cellular responsiveness to MSH, also enhanced expression of internal binding sites. The results indicate that expression of internal binding sites for MSH is an important criterion for cellular responsiveness to the hormone.

  4. Structural basis for the evolutionary inactivation of Ca[superscript 2+] binding to synaptotagmin 4

    SciTech Connect (OSTI)

    Dai, Han; Shin, Ok-Ho; Machius, Mischa; Tomchick, Diana R.; Sdhof, Thomas C.; Rizo, Josep (U. of Texas-SMED)

    2010-11-16T23:59:59.000Z

    The neuronal protein synaptotagmin 1 functions as a Ca{sup 2+} sensor in exocytosis via two Ca{sup 2+}-binding C{sub 2} domains. The very similar synaptotagmin 4, which includes all the predicted Ca{sup 2+}-binding residues in the C{sub 2}B domain but not in the C{sub 2}A domain, is also thought to function as a neuronal Ca{sup 2+} sensor. Here we show that, unexpectedly, both C{sub 2} domains of fly synaptotagmin 4 exhibit Ca{sup 2+}-dependent phospholipid binding, whereas neither C{sub 2} domain of rat synaptotagmin 4 binds Ca{sup 2+} or phospholipids efficiently. Crystallography reveals that changes in the orientations of critical Ca{sup 2+} ligands, and perhaps their flexibility, render the rat synaptotagmin 4 C{sub 2}B domain unable to form full Ca{sup 2+}-binding sites. These results indicate that synaptotagmin 4 is a Ca{sup 2+} sensor in the fly but not in the rat, that the Ca{sup 2+}-binding properties of C{sub 2} domains cannot be reliably predicted from sequence analyses, and that proteins clearly identified as orthologs may nevertheless have markedly different functional properties.

  5. Binding of He{sub n}V clusters to ?-Fe grain boundaries

    SciTech Connect (OSTI)

    Tschopp, M. A., E-mail: mark.a.tschopp.civ@mail.mil [U.S. Army Research Laboratory, Aberdeen Proving Ground, Maryland 21005 (United States); Gao, F. [Pacific Northwest National Laboratory, Richland, Washington 99352 (United States); Solanki, K. N. [Arizona State University, Tempe, Arizona 85287 (United States)

    2014-06-21T23:59:59.000Z

    The objective of this research is to explore the formation/binding energetics and length scales associated with the interaction between He{sub n}V clusters and grain boundaries in bcc ?-Fe. In this work, we calculated formation/binding energies for 18 He atoms in a monovacancy at all potential grain boundary (GB) sites within 15? of the ten grain boundaries selected (122106 simulations total). The present results provide detailed information about the interaction energies and length scales of 18 He atoms with grain boundaries for the structures examined. A number of interesting new findings emerge from the present study. First, the ?3(112) twin GB has significantly lower binding energies for all He{sub n}V clusters than all other boundaries in this study. For all grain boundary sites, the effect of the local environment surrounding each site on the He{sub n}V formation and binding energies decreases with an increasing number of He atoms in the He{sub n}V cluster. Based on the calculated dataset, we formulated a model to capture the evolution of the formation and binding energy of He{sub n}V clusters as a function of distance from the GB center, utilizing only constants related to the maximum binding energy and the length scale.

  6. Binding proteins for growth hormone and prolactin in rabbit kidney cytosol

    SciTech Connect (OSTI)

    Herington, A.C.; Stevenson, J.L.; Ymer, S.I. (Prince Henry's Hospital, Melbourne (Australia))

    1988-09-01T23:59:59.000Z

    Two soluble, receptor-like binding proteins with apparent somatotrophic (growth hormone (GH)) and lactogenic (prolactin (PRL)) specificities, respectively, and that are present in rabbit kidney cytosol have now been examined in more detail using specific GH receptor and PRL receptor monoclonal antibodies (MAb). Gel chromatography of {sup 125}I-labeled human GH ({sup 125}I-hGH) kidney cytosol complexes in the absence of these MAbs revealed two specifically bound regions of radioactivity at molecular weights (MW) of {approximately}120,000 and {approximately}60,000, which are similar in size to complexes formed by the native GH receptor of rabbit liver cytosol and the PRL receptor of mammary gland. Co-incubation with GH-receptor MAb inhibited {sup 125}I-hGH binding only to the higher MW (120,000) species, whereas the PRL-receptor MAb inhibited only the lower MW (60,000) species, thus establishing definitively the hormonal specificities of the two binding proteins. The presence of both GH- and PRL-specific binding subunits in cytosol was confirmed using covalent cross-linking techniques. No GH binding protein was detected in kidney membranes. The presence of naturally soluble, receptor-like binding proteins for GH and PRL in kidney cytosol preparations raises the possibility of their playing a role in the intracellular regulation of kidney function and/or metabolism.

  7. Nucleotide Binding Site Communication in Arabidopsis thaliana Adenosine 5;-Phosphosulfate Kinase

    SciTech Connect (OSTI)

    Ravilious, Geoffrey E.; Jez, Joseph M. (WU)

    2012-08-31T23:59:59.000Z

    Adenosine 5{prime}-phosphosulfate kinase (APSK) catalyzes the ATP-dependent synthesis of adenosine 3{prime}-phosphate 5{prime}-phosphosulfate (PAPS), which is an essential metabolite for sulfur assimilation in prokaryotes and eukaryotes. Using APSK from Arabidopsis thaliana, we examine the energetics of nucleotide binary and ternary complex formation and probe active site features that coordinate the order of ligand addition. Calorimetric analysis shows that binding can occur first at either nucleotide site, but that initial interaction at the ATP/ADP site was favored and enhanced affinity for APS in the second site by 50-fold. The thermodynamics of the two possible binding models (i.e. ATP first versus APS first) differs and implies that active site structural changes guide the order of nucleotide addition. The ligand binding analysis also supports an earlier suggestion of intermolecular interactions in the dimeric APSK structure. Crystallographic, site-directed mutagenesis, and energetic analyses of oxyanion recognition by the P-loop in the ATP/ADP binding site and the role of Asp136, which bridges the ATP/ADP and APS/PAPS binding sites, suggest how the ordered nucleotide binding sequence and structural changes are dynamically coordinated for catalysis.

  8. Internal strain regulates the nucleotide binding site of the kinesin leading head

    E-Print Network [OSTI]

    Hyeon, Changbong; 10.1073/pnas.0610939104

    2009-01-01T23:59:59.000Z

    In the presence of ATP, kinesin proceeds along the protofilament of microtubule by alternated binding of two motor domains on the tubulin binding sites. Since the processivity of kinesin is much higher than other motor proteins, it has been speculated that there exists a mechanism for allosteric regulation between the two monomers. Recent experiments suggest that ATP binding to the leading head domain in kinesin is regulated by the rearward strain built on the neck-linker. We test this hypothesis by explicitly modeling a $C_{\\alpha}$-based kinesin structure whose both motor domains are bound on the tubulin binding sites. The equilibrium structures of kinesin on the microtubule show disordered and ordered neck-linker configurations for the leading and the trailing head, respectively. The comparison of the structures between the two heads shows that several native contacts present at the nucleotide binding site in the leading head are less intact than those in the binding site of the rear head. The network of n...

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

    SciTech Connect (OSTI)

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

    2014-10-02T23:59:59.000Z

    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.

  10. Divergence of Pumilio/fem-3 mRNA Binding Factor (PUF) Protein Specificity through Variations in an RNA-binding

    E-Print Network [OSTI]

    Sheridan, Jennifer

    sequence feature. Importantly, other PUF proteins lack the pocket and so do not discriminate upstream bases. A structure-based alignment reveals that these proteins lack key residues that would contact the cytosineDivergence of Pumilio/fem-3 mRNA Binding Factor (PUF) Protein Specificity through Variations

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

    E-Print Network [OSTI]

    Zeng, Bin

    2009-05-15T23:59:59.000Z

    with the parasitophorous vacuole membrane (PVM), which implies that this protein may be involved in lipid remodelling in the PVM, or in the transport of fatty acids across the membrane. We also identified two distinct oxysterol binding protein (OSBP)-related proteins (ORPs...

  12. Analysis of the hormone-binding domain of steroid receptors using chimeras generated by homologous recombination

    SciTech Connect (OSTI)

    Martinez, Elisabeth D. [Department of Biochemistry and Molecular Biology, Georgetown University School of Medicine, Washington, DC 20057 (United States); Pattabiraman, Nagarajan [Department of Biochemistry and Molecular Biology, Georgetown University School of Medicine, Washington, DC 20057 (United States); Department of Oncology, Georgetown University School of Medicine, Washington, DC 20057 (United States); Danielsen, Mark [Department of Biochemistry and Molecular Biology, Georgetown University School of Medicine, Washington, DC 20057 (United States)]. E-mail: dan@bc.georgetown.edu

    2005-08-15T23:59:59.000Z

    The glucocorticoid receptor and the mineralocorticoid receptor are members of the steroid receptor family that exhibit ligand cross-reactivity. Specificity of steroid receptor action is investigated in the present work by the construction and characterization of chimeras between the glucocorticoid receptor and the mineralocorticoid receptor. We used an innovative approach to make novel steroid receptor proteins in vivo that in general, contrary to our expectations, show increased ligand specificity compared to the parental receptors. We describe a receptor that is specific for the potent synthetic glucocorticoid triamcinolone acetonide and does not bind aldosterone. A further set of chimeras has an increased ability to discriminate between ligands, responding potently to mineralocorticoids and only very weakly to synthetic glucocorticoids. A chimera with the fusion site in the hinge highlights the importance of the region between the DNA-binding and the hormone-binding domains since, unlike both the glucocorticoid and mineralocorticoid receptors, it only responds to mineralocorticoids. One chimera has reduced specificity in that it acts as a general corticoid receptor, responding to glucocorticoids and mineralocorticoids with similar potency and efficacy. Our data suggest that regions of the glucocorticoid and mineralocorticoid receptor hormone-binding domains are functionally non-reciprocal. We present transcriptional, hormone-binding, and structure-modeling evidence that suggests that receptor-specific interactions within and across domains mediate aspects of specificity in transcriptional responses to steroids.

  13. Analytic, non-perturbative, gauge-invariant quantum chromodynamics: Nucleon scattering and binding potentials

    SciTech Connect (OSTI)

    Fried, H.M. [Physics Department, Brown University, Providence, RI 02912 (United States)] [Physics Department, Brown University, Providence, RI 02912 (United States); Gabellini, Y.; Grandou, T. [Universit de Nice Sophia-Antipolis, Institut Non Linaire de Nice, UMR 6618 CNRS, 06560 Valbonne (France)] [Universit de Nice Sophia-Antipolis, Institut Non Linaire de Nice, UMR 6618 CNRS, 06560 Valbonne (France); Sheu, Y.-M., E-mail: ymsheu@alumni.brown.edu [Universit de Nice Sophia-Antipolis, Institut Non Linaire de Nice, UMR 6618 CNRS, 06560 Valbonne (France)

    2013-11-15T23:59:59.000Z

    Removal of the quenched approximation in the mechanism which produced an analytic estimate of quark-binding potentials, along with a reasonable conjecture of the color structure of the nucleon formed by such a binding potential, is shown to generate an effective nucleon scattering and binding potential. The mass-scale factor on the order of the pion mass, previously introduced to define the transverse imprecision of quark coordinates, is again used, while the strength of the potential is proportional to the square of a renormalized quantum chromodynamics (QCD) coupling constant. The potential so derived does not include corrections due to spin, angular momentum, nucleon structure, and electroweak interactions; rather, it is qualitative in nature, showing how Nuclear Physics can arise from fundamental QCD. -- Highlights: Nucleonnucleon forces are derived qualitatively from basic realistic quantum chromodynamics. An effective nucleon binding is obtained from the simplest unquenched approximation. A model deuteron binding energy of ?2.2 MeV follows with ?{sub s,R}=12.5.

  14. Nonspecific transcription factor binding reduces variability in transcription factor and target protein expression

    E-Print Network [OSTI]

    Mohammad Soltani; Pavol Bokes; Zachary Fox; Abhyudai Singh

    2015-04-14T23:59:59.000Z

    Transcription factors (TFs) interact with a multitude of binding sites on DNA and partner proteins inside cells. We investigate how nonspecific binding/unbinding to such decoy binding sites affects the magnitude and time-scale of random fluctuations in TF copy numbers arising from stochastic gene expression. A stochastic model of TF gene expression, together with decoy site interactions is formulated. Distributions for the total (bound and unbound) and free (unbound) TF levels are derived by analytically solving the chemical master equation under physiologically relevant assumptions. Our results show that increasing the number of decoy binding sides considerably reduces stochasticity in free TF copy numbers. The TF autocorrelation function reveals that decoy sites can either enhance or shorten the time-scale of TF fluctuations depending on model parameters. To understand how noise in TF abundances propagates downstream, a TF target gene is included in the model. Intriguingly, we find that noise in the expression of the target gene decreases with increasing decoy sites for linear TF-target protein dose-responses, even in regimes where decoy sites enhance TF autocorrelation times. Moreover, counterintuitive noise transmissions arise for nonlinear dose-responses. In summary, our study highlights the critical role of molecular sequestration by decoy binding sites in regulating the stochastic dynamics of TFs and target proteins at the single-cell level.

  15. Beyond position weight matrices: nucleotide correlations in transcription factor binding sites and their description

    E-Print Network [OSTI]

    Santolini, Marc; Hakim, Vincent

    2013-01-01T23:59:59.000Z

    The identification of transcription factor binding sites (TFBSs) on genomic DNA is of crucial importance for understanding and predicting regulatory elements in gene networks. TFBS motifs are commonly described by Position Weight Matrices (PWMs), in which each DNA base pair independently contributes to the transcription factor (TF) binding, despite mounting evidence of interdependence between base pairs positions. The recent availability of genome-wide data on TF-bound DNA regions offers the possibility to revisit this question in detail for TF binding {\\em in vivo}. Here, we use available fly and mouse ChIPseq data, and show that the independent model generally does not reproduce the observed statistics of TFBS, generalizing previous observations. We further show that TFBS description and predictability can be systematically improved by taking into account pairwise correlations in the TFBS via the principle of maximum entropy. The resulting pairwise interaction model is formally equivalent to the disordered ...

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

    E-Print Network [OSTI]

    Zulfiqar Ahmad

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

  17. The N-terminal domain determines the affinity and specificity of H1 binding to chromatin

    SciTech Connect (OSTI)

    Oeberg, Christine, E-mail: christine.oberg@ki.se [Karolinska Institute, Department of Cell and Molecular Biology, P.O. Box 285, SE-17177 Stockholm (Sweden)] [Karolinska Institute, Department of Cell and Molecular Biology, P.O. Box 285, SE-17177 Stockholm (Sweden); Belikov, Sergey, E-mail: sergey.belikov@ki.se [Karolinska Institute, Department of Cell and Molecular Biology, P.O. Box 285, SE-17177 Stockholm (Sweden)] [Karolinska Institute, Department of Cell and Molecular Biology, P.O. Box 285, SE-17177 Stockholm (Sweden)

    2012-04-06T23:59:59.000Z

    Highlights: Black-Right-Pointing-Pointer wt Human histone H1.4 and hH1.4 devoid of N-terminal domain, {Delta}N-hH1.4, were compared. Black-Right-Pointing-Pointer Both histones bind to chromatin, however, {Delta}N-hH1.4 displays lower binding affinity. Black-Right-Pointing-Pointer Interaction of {Delta}N-hH1.4 with chromatin includes a significant unspecific component. Black-Right-Pointing-Pointer N-terminal domain is a determinant of specificity of histone H1 binding to chromatin. -- Abstract: Linker histone H1, one of the most abundant nuclear proteins in multicellular eukaryotes, is a key component of the chromatin structure mainly due to its role in the formation and maintenance of the 30 nm chromatin fiber. It has a three-domain structure; a central globular domain flanked by a short N-terminal domain and a long, highly basic C-terminal domain. Previous studies have shown that the binding abilities of H1 are at large determined by the properties of the C-terminal domain; much less attention has been paid to role of the N-terminal domain. We have previously shown that H1 can be reconstituted via cytoplasmic mRNA injection in Xenopus oocytes, cells that lack somatic H1. The heterologously expressed H1 proteins are incorporated into in vivo assembled chromatin at specific sites and the binding event is monitored as an increase in nucleosomal repeat length (NRL). Using this setup we have here compared the binding properties of wt-H1.4 and hH1.4 devoid of its N-terminal domain ({Delta}N-hH1.4). The {Delta}N-hH1.4 displays a drastically lower affinity for chromatin binding as compared to the wild type hH1.4. Our data also indicates that {Delta}N-hH1.4 is more prone to unspecific chromatin binding than the wild type. We conclude that the N-terminal domain of H1 is an important determinant of affinity and specificity of H1-chromatin interactions.

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

    E-Print Network [OSTI]

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

    2012-03-20T23:59:59.000Z

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

  19. Sclerostin binds and regulates the activity of cysteine-rich protein 61

    SciTech Connect (OSTI)

    Craig, Theodore A. [Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN 55905 (United States)] [Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN 55905 (United States); Bhattacharya, Resham; Mukhopadhyay, Debabrata [Department of Biochemistry and Molecular Biology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905 (United States)] [Department of Biochemistry and Molecular Biology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905 (United States); Kumar, Rajiv, E-mail: rkumar@mayo.edu [Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN 55905 (United States) [Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN 55905 (United States); Department of Biochemistry and Molecular Biology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905 (United States)

    2010-01-29T23:59:59.000Z

    Sclerostin, a secreted glycoprotein, regulates osteoblast function. Using yeast two-hybrid and direct protein interaction analyses, we demonstrate that sclerostin binds the Wnt-modulating and Wnt-modulated, extracellular matrix protein, cysteine-rich protein 61 (Cyr61, CCN1), which regulates mesenchymal stem cell proliferation and differentiation, osteoblast and osteoclast function, and angiogenesis. Sclerostin was shown to inhibit Cyr61-mediated fibroblast attachment, and Cyr61 together with sclerostin increases vascular endothelial cell migration and increases osteoblast cell division. The data show that sclerostin binds to and influences the activity of Cyr61.

  20. Importance of the Doppler Effect to the Determination of the Deuteron Binding Energy

    E-Print Network [OSTI]

    Yongkyu Ko; Myung Ki Cheoun; Il-Tong Cheon

    1999-04-01T23:59:59.000Z

    The deuteron binding energy extracted from the reaction ${}^1H(n,\\gamma){}^2H$ is reviewed with the exact relativistic formula, where the initial kinetic energy and the Doppler effect are taken into account. We find that the negligible initial kinetic energy of the neutron could cause a significant uncertainty which is beyond the errors available up to now. Therefore, we suggest an experiment which should include the detailed informations about the initial kinetic energy and the detection angle. It could reduce discrepancies among the recently reported values about the deuteron binding energy and pin down the uncertainty due to the Doppler broadening of $\\gamma$ ray.

  1. AK---------Adaptive Kernel estimates of home-range BLM-------Bureau of Land Management (USDI)

    E-Print Network [OSTI]

    Standiford, Richard B.

    Conservation Areas IPs --------- Industrial Private (Timber Companies) ISC -------- Interagency Scientific

  2. Identification of a Unique Ganglioside Binding Loop within Botulinum Neurotoxins C and D-SA

    SciTech Connect (OSTI)

    Karalewitz, Andrew P.-A.; Kroken, Abby R.; Fu, Zhuji; Baldwin, Michael R.; Kim, Jung-Ja P.; Barbieri, Joseph T. (MCW); (Missouri)

    2010-09-22T23:59:59.000Z

    The botulinum neurotoxins (BoNTs) are the most potent protein toxins for humans. There are seven serotypes of BoNTs (A-G) based on a lack of cross antiserum neutralization. BoNTs utilize gangliosides as components of the host receptors for binding and entry into neurons. Members of BoNT/C and BoNT/D serotypes include mosaic toxins that are organized in D/C and C/D toxins. One D/C mosaic toxin, BoNT/D-South Africa (BoNT/D-SA), was not fully neutralized by immunization with BoNT serotype C or D, which stimulated this study. Here the crystal structures of the receptor binding domains of BoNT/C, BoNT/D, and BoNT/D-SA are presented. Biochemical and cell binding studies show that BoNT/C and BoNT/D-SA possess unique mechanisms for ganglioside binding. These studies provide new information about how the BoNTs can enter host cells as well as a basis for understanding the immunological diversity of these neurotoxins.

  3. Plasmon-Waveguide Resonance Studies of Ligand Binding to the Human 2-Adrenergic Receptor

    E-Print Network [OSTI]

    Kobilka, Brian

    Plasmon-Waveguide Resonance Studies of Ligand Binding to the Human 2-Adrenergic Receptor SavithaVed October 8, 2003; ReVised Manuscript ReceiVed December 12, 2003 ABSTRACT: Plasmon-waveguide resonance (PWR activation in the 2-AR (7- 9). For the human -opioid receptor, plasmon-waveguide resonance (PWR) spectroscopy

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

    SciTech Connect (OSTI)

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

    2009-02-20T23:59:59.000Z

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

  5. Box: Interdependent Modes of Binding in a Two-Nanometer-Long Synthetic Receptor

    E-Print Network [OSTI]

    Goddard III, William A.

    ,6-dinitrotoluene, 1,2,4- trichlorobenzene, and both the 9,10- and 1,4-anthraquinone molecules. Moreover, Ex2 Box4 the different modes of binding of Ex2 Box4+ with anthracene, 9,10-anthraquinone, and 1,4-anthraquinone in order

  6. A new interpretation of the proton-neutron bound state. The calculation of the binding energy

    E-Print Network [OSTI]

    N. B. Mandache

    1996-12-01T23:59:59.000Z

    We treat the old problem of the proton-neutron bound state (the deuteron). Using a new concept of incomplete (partial) annihilation process we derive a formula for the binding energy of the deuteron, which does not contain any new constant. Some implications of this new approach are discussed.

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

    E-Print Network [OSTI]

    Forbes, Douglass

    Inhibition of In Vitro Nuclear Transport by a Lectin that Binds to Nuclear Pores Deborah R. Finlay to investigate the molecular mechanism of nuclear transport, we used an in vitro transport system com- posed of a Xenopus egg extract, rat liver nuclei, and a fluorescently labeled nuclear protein, nucleoplasmin

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

    E-Print Network [OSTI]

    Fernndez de Crdoba, Pedro

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

  9. Agonist-Activated Glucocorticoid Receptor Inhibits Binding of Heat Shock Factor 1 to the Heat Shock

    E-Print Network [OSTI]

    Abraham, Nader G.

    Agonist-Activated Glucocorticoid Receptor Inhibits Binding of Heat Shock Factor 1 to the Heat Shock- cocorticoid receptor (GR) signaling in stressed cells will cause inhibition of the heat shock re- sponse as mediated by heat shock transcription factor 1 (HSF1). In that work, a full-length human heat shock protein

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

    E-Print Network [OSTI]

    Boyer, Edmond

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

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

    SciTech Connect (OSTI)

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

    1985-11-01T23:59:59.000Z

    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.

  12. Computational design of an endo-1,4-[beta]-xylanase ligand binding site

    SciTech Connect (OSTI)

    Morin, Andrew; Kaufmann, Kristian W.; Fortenberry, Carie; Harp, Joel M.; Mizoue, Laura S.; Meiler, Jens (Vanderbilt)

    2012-09-05T23:59:59.000Z

    The field of computational protein design has experienced important recent success. However, the de novo computational design of high-affinity protein-ligand interfaces is still largely an open challenge. Using the Rosetta program, we attempted the in silico design of a high-affinity protein interface to a small peptide ligand. We chose the thermophilic endo-1,4-{beta}-xylanase from Nonomuraea flexuosa as the protein scaffold on which to perform our designs. Over the course of the study, 12 proteins derived from this scaffold were produced and assayed for binding to the target ligand. Unfortunately, none of the designed proteins displayed evidence of high-affinity binding. Structural characterization of four designed proteins revealed that although the predicted structure of the protein model was highly accurate, this structural accuracy did not translate into accurate prediction of binding affinity. Crystallographic analyses indicate that the lack of binding affinity is possibly due to unaccounted for protein dynamics in the 'thumb' region of our design scaffold intrinsic to the family 11 {beta}-xylanase fold. Further computational analysis revealed two specific, single amino acid substitutions responsible for an observed change in backbone conformation, and decreased dynamic stability of the catalytic cleft. These findings offer new insight into the dynamic and structural determinants of the {beta}-xylanase proteins.

  13. Oligomerization of peptides LVEALYL and RGFFYT and their binding affinity to insulin

    E-Print Network [OSTI]

    , Taipei 11529, Taiwan 3 Institute for Computational Science and Technology, 6 Quarter, Linh Trung Ward that LVEALYL can aggregate. Theoretical estimation of the binding free energy of LVEALYL to insulin) and chain B (30 residues) [6] connected by two inter-disulfide bonds. Its native state is a predominantly

  14. Calculations of the binding affinities of protein-protein complexes with the fast multipole method

    E-Print Network [OSTI]

    Song, Xueyu

    Calculations of the binding affinities of protein-protein complexes with the fast multipole method the boundary element method in combination with the fast multipole method. The residue level model with the fast multipole method allows us to efficiently investigate how the mutations on the active site

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

    E-Print Network [OSTI]

    Luhua, Lai

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

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

    E-Print Network [OSTI]

    Fainzilber, Michael

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

  17. Grafting odorant binding proteins on diamond bio-MEMS R. Manai a,

    E-Print Network [OSTI]

    Boyer, Edmond

    . Beside, cantilevers based on polycrystalline diamond surfaces are very promising as chemical transducers. Here two methods were investigated for chemically grafting porcine OBPs onto polycrystalline diamond1 Grafting odorant binding proteins on diamond bio-MEMS R. Manai a, *, E. Scorsone a , L. Rousseau

  18. Regulation of Neurexin 1[beta] Tertiary Structure and Ligand Binding through Alternative Splicing

    SciTech Connect (OSTI)

    Shen, Kaiser C.; Kuczynska, Dorota A.; Wu, Irene J.; Murray, Beverly H.; Sheckler, Lauren R.; Rudenko, Gabby (Michigan)

    2008-08-04T23:59:59.000Z

    Neurexins and neuroligins play an essential role in synapse function, and their alterations are linked to autistic spectrum disorder. Interactions between neurexins and neuroligins regulate inhibitory and excitatory synaptogenesis in vitro through a splice-insert signaling code. In particular, neurexin 1{beta} carrying an alternative splice insert at site SS{number_sign}4 interacts with neuroligin 2 (found predominantly at inhibitory synapses) but much less so with other neuroligins (those carrying an insert at site B and prevalent at excitatory synapses). The structure of neurexin 1{beta}+SS{number_sign}4 reveals dramatic rearrangements to the 'hypervariable surface', the binding site for neuroligins. The splice insert protrudes as a long helix into space, triggers conversion of loop {beta}10-{beta}11 into a helix rearranging the binding site for neuroligins, and rearranges the Ca{sup 2+}-binding site required for ligand binding, increasing its affinity. Our structures reveal the mechanism by which neurexin 1{beta} isoforms acquire neuroligin splice isoform selectivity.

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

    E-Print Network [OSTI]

    Meller, Amit

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

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

    DOE Patents [OSTI]

    Shoseyov, O.; Yosef, K.

    1998-04-14T23:59:59.000Z

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

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

    DOE Patents [OSTI]

    Shoseyov, Oded (Karmey Yosef, IL)

    1998-01-01T23:59:59.000Z

    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.

  2. Quantum confined Stark effect in Gaussian quantum wells: A tight-binding study

    SciTech Connect (OSTI)

    Ramrez-Morales, A.; Martnez-Orozco, J. C.; Rodrguez-Vargas, I. [Unidad Acadmica de Fsica, Universidad Autnoma de Zacatecas, Calzada Solidaridad Esquina Con Paseo La Bufa S/N, 98060 Zacatecas, Zac. (Mexico)

    2014-05-15T23:59:59.000Z

    The main characteristics of the quantum confined Stark effect (QCSE) are studied theoretically in quantum wells of Gaussian profile. The semi-empirical tight-binding model and the Green function formalism are applied in the numerical calculations. A comparison of the QCSE in quantum wells with different kinds of confining potential is presented.

  3. Phosphorylation Regulates Assembly of the Caspase-6 Substrate-Binding Groove

    E-Print Network [OSTI]

    Hardy, Jeanne

    Structure Article Phosphorylation Regulates Assembly of the Caspase-6 Substrate-Binding Groove Elih M. Vela zquez-Delgado1 and Jeanne A. Hardy1,* 1Department of Chemistry, University of Massachusetts's and Alzheimer's diseases. A full understanding of caspase-6 regulation is crucial to caspase-6- specific

  4. Chromosome-Biased Binding and Gene Regulation by the Caenorhabditis elegans DRM Complex

    E-Print Network [OSTI]

    Horvitz, H. Robert

    Chromosome-Biased Binding and Gene Regulation by the Caenorhabditis elegans DRM Complex Tomoko M Medicine and Program in Cell Dynamics, University of Massachusetts Medical School, Worcester, Massachusetts, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America, 3 Howard

  5. IN VITRO METABOLISM OF ZERANOL: EVALUATION OF COVALENT BINDING TO MICROSOMAL PROTEIN

    E-Print Network [OSTI]

    Paris-Sud XI, Université de

    ). In contrast, for zeranol there is no information about the production of reactive metabolites of reactive metabolite production and of possible covalent binding of zeranol metabolite(s) to proteins using using a Beckmann ultracentrifuge (rotor 50). The microsomal pellet was suspended in 10 volumes of KCI

  6. 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. (Puerto Rico); (HHMI); (Texas)

    2012-09-17T23:59:59.000Z

    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.

  7. Notch and MAML-1 Complexation Do Not Detectably Alter the DNA Binding Specificity of the Transcription

    E-Print Network [OSTI]

    Bulyk, Martha L.

    States of America Abstract Background: Canonical Notch signaling is initiated when ligand binding induces of Health/National Human Genome Research Institute to M.L.B. and grant # R01 CA092433 to S.C.B. The funders-mail: sblacklow@partners.org (SCB); mlbulyk@receptor.med.harvard.edu (MLB) a Current address: Cibio Centro

  8. Disordered graphene and boron nitride in a microwave tight-binding analogue S. Barkhofen,1

    E-Print Network [OSTI]

    Paris-Sud XI, Universit de

    Disordered graphene and boron nitride in a microwave tight-binding analogue S. Barkhofen,1 M Sophia-Antipolis, 06108 Nice, France (Dated: December 20, 2012) Experiments on hexagonal graphene of the high flexibility of the discs positions, consequences of the disorder introduced in the graphene

  9. Annu. Rev. Biophys. Biomol. Struct. 1998. 27:10531 MINOR GROOVE-BINDING

    E-Print Network [OSTI]

    Clore, G. Marius

    by architectural proteins that typically lack the potential to activate transcription or carry out recombinationAnnu. Rev. Biophys. Biomol. Struct. 1998. 27:10531 MINOR GROOVE-BINDING ARCHITECTURAL PROTEINS protein, HMG-box proteins, integration host factor, HMG I(Y), DNA bending ABSTRACT To date, high

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

    E-Print Network [OSTI]

    Lebendiker, Mario

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

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

    E-Print Network [OSTI]

    Weston, Ken

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

  12. Determination of Binding Constants of Cyclodextrins in Room-Temperature Ionic Liquids

    E-Print Network [OSTI]

    Reid, Scott A.

    unique chemical and physical properties, including being air and moisture stable, a high solubility power with supercritical fluid CO2;9-11 (4) electrochemical reactions;12,13 and (5) as a medium for enzymatic reactions.14Determination of Binding Constants of Cyclodextrins in Room-Temperature Ionic Liquids by Near

  13. Eur. J. Biochem. 78, 585-598 (1977) Binding of Modified Adenine Nucleotides

    E-Print Network [OSTI]

    Govindjee

    Eur. J. Biochem. 78, 585-598 (1977) Binding of Modified Adenine Nucleotides to Isolated Coupling) 1. Fluorescent nucleotides (1,N6-ethenoadenosine diphosphate and triphosphate, EADP and EATP)replace the natural nucleotides rather efficiently (65- 85%) in several chloroplast reactions (ADP inhibition

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

    E-Print Network [OSTI]

    California at Berkeley, University of

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

  15. Screening Libraries To Identify Proteins with Desired Binding Activities Using a Split-GFP

    E-Print Network [OSTI]

    Shorter, James

    Screening Libraries To Identify Proteins with Desired Binding Activities Using a Split 06520 cbi9990825210008 W e have previously described a split-green fluorescent protein (GFP) reassembly assay by which to detect protein protein interac- tions (1-3). In this assay, green fluorescent protein

  16. Biophysical characterization of SipA, an actin-binding protein from Salmonella enterica

    E-Print Network [OSTI]

    Galan, Jorge E

    , CT 06510, USA b Section of Microbial Pathogenesis, Boyer Center for Molecular Medicine, Yale dynamics by directly binding to F-actin. We have biophysically characterized a C-terminal fragment, SipA446 a model that is consistent with the observed effects of SipA446684 on actin dynamics and F

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

    E-Print Network [OSTI]

    Mario-Ramrez, Leonardo

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

  18. The First Example of a Nitrile Hydratase Model Complex that Reversibly Binds Nitriles

    E-Print Network [OSTI]

    Kaminsky, Werner

    with both methanol and acetonitrile to afford a six-coordinate solvent-bound complex. Competitive binding for acetonitrile (H ) -6.2((0.2) kcal/mol, S ) -29.4((0.8) eu), benzonitrile (-4.2((0.6) kcal/mol, S ) -18((3) eu-temperature electronic absorption spectroscopy. Ligand exchange kinetics were examined for acetonitrile, iso

  19. Reading of DNA Sequence Logos: Prediction of Major Groove Binding by Information

    E-Print Network [OSTI]

    Schneider, Thomas D.

    Reading of DNA Sequence Logos: Prediction of Major Groove Binding by Information Theory Thomas D: http://www.lecb.ncifcrf.gov/~toms/how.to.read.sequence.logos/index.html running title: Reading Sequence Logos #3; National Cancer Institute, Frederick Cancer Research and Development Center, Lab- oratory

  20. Europium-Doped TiO2 Hollow Nanoshells: Two-Photon Imaging of Cell Binding

    E-Print Network [OSTI]

    Kummel, Andrew C.

    Europium-Doped TiO2 Hollow Nanoshells: Two-Photon Imaging of Cell Binding Sergio Sandoval,,, Jian method to fabricate luminescent monodisperse 200 nm europium-doped hollow TiO2 nanoshell (NS) particles-functionalized polystyrene beads were used as templates, and the porous walls of europium-doped titania nanoshells were

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

    SciTech Connect (OSTI)

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

    2011-12-31T23:59:59.000Z

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

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

    E-Print Network [OSTI]

    Ferguson, Scarlett Blair

    2012-10-19T23:59:59.000Z

    diphosphate (MgADP). PEP and MgADP bind to the same allosteric binding site but exhibit opposite effects, PEP acting as an inhibitor and MgADP an activator. In 2005, Parichatttanakul, et al. solved the first crystal structure of LbPFK to 1.87 A resolution...

  3. PAPER www.rsc.org/obc | Organic & Biomolecular Chemistry RNA binding and thiolytic stability of a quinoline-containing

    E-Print Network [OSTI]

    Beal, Peter A.

    as the intercalation domain. A quinoline-containing HTP is shown to bind selectively to duplex RNA binding sites influences the affinity of these compounds for RNA targets. Our original HTP design used 9- anilinoacridines a new HTP design that uses quinoline for intercalation. A high yielding synthesis to a new quinoline

  4. 1246 J. Am. Chem. SOC. 1995, 117, 1246-1257 RNA Aptamers That Bind Flavin and Nicotinamide Redox

    E-Print Network [OSTI]

    Heller, Eric

    that specifically bind riboflavin (Rb) and P-nicotinamide mononucleotide (NMN) have been isolated by in vitro to oxidized riboflavin (& = 1-5 pM). DNA versions of the consensus sequence also bind, but with weaker structural analog of riboflavin. In contrast to the lack of redox specificity of the riboflavin aptamers

  5. Dirac Point and Edge States in a Microwave Realization of Tight-Binding Graphene-like Structures

    E-Print Network [OSTI]

    Boyer, Edmond

    Dirac Point and Edge States in a Microwave Realization of Tight-Binding Graphene-like Structures U-binding graphene-like structures. The structures are realized using disks with a high index of refraction properties, mechan- ically as electronically. Another realization is graphene, a one-atom-thick allotrope

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

    E-Print Network [OSTI]

    Ramos, Joe W.

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

  7. Interaction of P-aminobenzoic acid with normal and sickel erythrocyte membrane: photoaffinity labelling of the binding sites

    SciTech Connect (OSTI)

    Premachandra, B.R.

    1986-03-05T23:59:59.000Z

    Electron microscopic studies revealed that P-Amino benzoic acid (PABA) could prevent eichinocytosis of red cells in vitro. Equilibrium binding studies with right side out membrane vesicles (ROV) revealed a similar number of binding sites (1.2-1.4 ..mu..mol/mg) and Kd (1.4-1.6 mM) values for both normal and sickle cell membranes. /sup 14/C-Azide analogue of PABA was synthesized as a photoaffinity label to probe its sites of interaction on the erythrocyte membranes. Competitive binding studies of PABA with its azide indicated that both the compounds share common binding sites on the membrane surface since a 20 fold excess of azide inhibited PABA binding in a linear fashion. The azide was covalently incorporated into the membrane components only upon irradiation (52-35% of the label found in the proteins and the rest in lipids). Electrophoretic analysis of photolabelled ROV revealed that the azide interacts chiefly with Band 3 protein. PABA inhibited both high and low affinity calcium (Ca) binding sites situated on either surface of the membrane in a non-competitive manner; however, Ca binding stimulated by Mg-ATP was not affected. Ca transport into inside out vesicles was inhibited by PABA; but it did not affect the calcium ATP-ase activity. The authors studies suggest that the mechanism of action of PABA is mediated by its interaction with Band 3 protein (anion channel), calcium channel and calcium binding sites of erythrocyte membrane.

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

    E-Print Network [OSTI]

    Weston, Ken

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

  9. Binding energies and electronic structures of adsorbed titanium chains on carbon nanotubes Chih-Kai Yang,1

    E-Print Network [OSTI]

    Binding energies and electronic structures of adsorbed titanium chains on carbon nanotubes Chih energy for both zigzag and armchair tubes. The delocalized 3d electrons from the titanium chain generate studied the binding energies and electronic structures of metal Ti, Al, Au chains adsorbed on single

  10. Oligomeric Status and Nucleotide Binding Properties of the Plastid ATP/ADP Transporter 1: Toward a Molecular

    E-Print Network [OSTI]

    Paris-Sud XI, Université de

    Oligomeric Status and Nucleotide Binding Properties of the Plastid ATP/ADP Transporter 1: Toward, was confirmed to be essential for nucleotide steady-state transport. Nucleotide binding studies and analysis is not essential for multimerization, but probably plays a regulatory role, controlling the nucleotide exchange

  11. The Glutamate Switch of Bacteriophage T7 DNA Helicase ROLE IN COUPLING NUCLEOTIDE TRIPHOSPHATE (NTP) AND DNA BINDING TO NTP

    E-Print Network [OSTI]

    Richardson, Charles C.

    The Glutamate Switch of Bacteriophage T7 DNA Helicase ROLE IN COUPLING NUCLEOTIDE TRIPHOSPHATE (NTP also creates nucleotide-binding sites located at the interfaces of the sub- units. DNA binding of a bound nucleoside 5 -triphosphate. However, in the absence of a nucleotide, Glu-343 changes orientation

  12. Caspase-3 binds diverse P4 residues in peptides as revealed by crystallography and structural modeling.

    SciTech Connect (OSTI)

    Fang, Bin; Fu, Guoxing; Agniswamy, Johnson; Harrison, Robert W.; Weber, Irene T.; (GSU)

    2009-03-31T23:59:59.000Z

    Caspase-3 recognition of various P4 residues in its numerous protein substrates was investigated by crystallography, kinetics, and calculations on model complexes. Asp is the most frequent P4 residue in peptide substrates, although a wide variety of P4 residues are found in the cellular proteins cleaved by caspase-3. The binding of peptidic inhibitors with hydrophobic P4 residues, or no P4 residue, is illustrated by crystal structures of caspase-3 complexes with Ac-IEPD-Cho, Ac-WEHD-Cho, Ac-YVAD-Cho, and Boc-D(OMe)-Fmk at resolutions of 1.9-2.6 {angstrom}. The P4 residues formed favorable hydrophobic interactions in two separate hydrophobic regions of the binding site. The side chains of P4 Ile and Tyr form hydrophobic interactions with caspase-3 residues Trp206 and Trp214 within a non-polar pocket of the S4 subsite, while P4 Trp interacts with Phe250 and Phe252 that can also form the S5 subsite. These interactions of hydrophobic P4 residues are distinct from those for polar P4 Asp, which indicates the adaptability of caspase-3 for binding diverse P4 residues. The predicted trends in peptide binding from molecular models had high correlation with experimental values for peptide inhibitors. Analysis of structural models for the binding of 20 different amino acids at P4 in the aldehyde peptide Ac-XEVD-Cho suggested that the majority of hydrophilic P4 residues interact with Phe250, while hydrophobic residues interact with Trp206, Phe250, and Trp214. Overall, the S4 pocket of caspase-3 exhibits flexible adaptation for different residues and the new structures and models, especially for hydrophobic P4 residues, will be helpful for the design of caspase-3 based drugs.

  13. Detection of a megabase deletion in a patient with brachio-oto-renal syndrome (BOR) and tricho-rhino-phalangeal syndrome (TRPS): Implications for mapping and cloning the BOR gene

    SciTech Connect (OSTI)

    Gu, J.Z.; Wells, D.E. [Univ. of Houston, TX (United States)] [Univ. of Houston, TX (United States); Wagner, M.J. [Glaxo Wellcome Inc., Research Triangle Park, NC (United States)] [Glaxo Wellcome Inc., Research Triangle Park, NC (United States); Haan, E.A. [Adelaide Children`s Hospital (Australia)] [Adelaide Children`s Hospital (Australia)

    1996-01-15T23:59:59.000Z

    Genetic linkage analysis has previously mapped the locus for the autosomal dominant disorder branchio-oto-renal syndrome (BOR) to the pericentric region of chromosome 8q. A YAC contig spanning the putative BOR region, from D8S543 to D8S541, was constructed and confirmed by sequence-tagged site content mapping using microsatellite markers and by DNA hybridization analysis. YACs spanning the BOR interval were used as fluorescence in situ hybridization probes on a cell line from a patient with BO and tricho-rhino-phalangeal syndrome I that involves a chromosome 8q rearrangement. In addition to the cytogenetically defined direct insertion of material from 8q13.3-q21.13 into 8q24.11, a previously unidentified deletion of just under one megabase was found in 8q13.3. These data narrowed the most likely location of the BOR gene to a region corresponding to the proximal two-thirds of YAC 869E10 between D8S543 and D8S279. 23 refs., 3 figs.

  14. Accurate Analysis of Large Datasets of Protein-Ligand Binding Geometries Using a Linear Clustering Method Based on MapReduce

    E-Print Network [OSTI]

    Maccabe, Barney

    are traditionally scored based on energy values. A protein-ligand complex selected because Accurate Analysis of Large Datasets of Protein-Ligand Binding Geometries for classifying protein-ligand binding geometries in molecular docking. We analyze results

  15. Structural Basis of Low-Affinity Nickel Binding to the Nickel-Responsive Transcription Factor NikR from Escherichia coli

    E-Print Network [OSTI]

    Phillips, Christine M.

    Escherichia coli NikR regulates cellular nickel uptake by binding to the nik operon in the presence of nickel and blocking transcription of genes encoding the nickel uptake transporter. NikR has two binding affinities for ...

  16. Elucidation of the Mechanisms of Nucleosome Binding and Repositioning by a Chromatin Remodeler: Monomeric ISWI Remodels Nucleosomes Through a Random Walk

    E-Print Network [OSTI]

    Al-Ani, Gada K.

    2014-05-31T23:59:59.000Z

    remodeler ISWI with fluorophore-labeled nucleosomes and DNA through associated changes in fluorescence anisotropy of the fluorophore upon ISWI binding to these substrates. We determined that one ISWI molecule binds to a 20 bp double stranded DNA substrate...

  17. 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.

    2006-12-12T23:59:59.000Z

    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.

  18. Translation Initiation Factors eIF-iso4G and eIF-4B Interact with the Poly(A)-binding Protein and Increase Its RNA Binding Activity*

    E-Print Network [OSTI]

    Tullos, Desiree

    Translation Initiation Factors eIF-iso4G and eIF-4B Interact with the Poly(A)-binding Protein (eIF-4F and eIF-iso4F) and eIF-4B, bind to the poly(A)-binding protein (PABP) both in the presence and absence of poly(A) RNA. The interactions between PABP and eIF- 4F, eIF-iso4F, and eIF-4B were measured

  19. Model for the Binding of the Inactivation N-Terminal to the Ion Pore of Shaker Potassium Channel: Both Electrostatic Attraction and Covalent Linkage Are Required for Rapid

    E-Print Network [OSTI]

    Weston, Ken

    Model for the Binding of the Inactivation N-Terminal to the Ion Pore of Shaker Potassium Channel; In Final Form: December 21, 2001 A model is presented for relating the binding of the inactivation N-terminal to the ion pore of the Shaker potassium channel (ShB) to the bimolecular binding of the N-terminal peptide

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

    E-Print Network [OSTI]

    Grter, Frauke

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

  1. 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

    2015-03-04T23:59:59.000Z

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

  2. Selective electrostatic binding of ions by monolayers of mercaptan derivatives adsorbed to gold substrates

    SciTech Connect (OSTI)

    Sun, Li; Johnson, B.; Wade, T.; Crooks, R.M. (Univ. of New Mexico, Albuquerque (USA))

    1990-12-27T23:59:59.000Z

    A single, self-assembled monolayer of organic material is used to impart pH-dependent electrostatic-based recognition capability to an Au electrode. The results show that 4-aminothiophenol and related mercaptans change the surface characteristics of naked Au toward the adsorption of positively and negatively charged ions as a function of pH. For example, anthraquinone-2,6-disulfonate irreversibly adsorbs to naked Au surfaces over a broad range of pH. However, a preadsorbed monolayer of 4-aminothiophenol prevents adsorption of anthraquinone-2,6-disulfonate at high pH but electrostatically binds it at low pH. The principle of pH-dependent binding is general for a number of amine-, carboxylic acid-, and pyridine-terminated mercaptan derivatives adsorbed to Au surfaces.

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

    DOE Patents [OSTI]

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

    2010-09-21T23:59:59.000Z

    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.

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

    SciTech Connect (OSTI)

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

    2012-02-07T23:59:59.000Z

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

  5. 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

    2007-03-13T23:59:59.000Z

    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).

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

    E-Print Network [OSTI]

    Christian Hainzl; Masao Hirokawa; Herbert Spohn

    2003-12-10T23:59:59.000Z

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

  7. The cooperative binding of spermine to SSB protein-poly(dT) complexes

    E-Print Network [OSTI]

    Wei, Tai-Fen

    1988-01-01T23:59:59.000Z

    mode conformation. The intrinsic binding constant (B) to the (SSB) binding mode is dependent upon NaC1 concentration, having values of 1. 80x10 M in 0. 1 mM NaC1, 1. 40x10 M in 5mM NaC1, and 6. 57x10 M in 10 mM NaCl, respectively. The allosteric... equilibrium constant (L) between the two SSB protein-ssDNA conformations is 1. 00 x 10 in 0. 1 mM NaC1, 5. 00 in 5 mM NaC1, and 5. 50 x 10 in 10 mM NaC1 indicating that cooperativity decreases as NaC1 concentration increases. Na+ acts as a competitor...

  8. Development of affinity technology for isolating individual human chromosomes by third strand binding

    SciTech Connect (OSTI)

    Fresco, Jacques R.

    2003-06-01T23:59:59.000Z

    The overall goal was to explore whether nucleic acid third strands could be used to bind with very high specificity to specific targets within whole genomes. Towards this end conditions had to be found to keep erroneous binding to an absolute minimum. The goal to use third strands (linked to magnetic beads) to ''capture'' large particles such as plasmids, cosmids, and whole chromosomes from complex mixtures was partially met; their use to serve as cytogenetic probes of metaphase chromosomes and to deliver reactive reagents to unique target sites on chromosomes in vivo for the purpose of mutagenizing specific base pairs was fully met; and their use as cytogenetic probes of chromosomal DNA in sections of formalin-fixed, paraffin-embedded tissue has been met since the DOE support was terminated.

  9. Alignment of RNA molecules: Binding energy and statistical properties of random sequences

    SciTech Connect (OSTI)

    Valba, O. V., E-mail: valbaolga@gmail.com [Moscow Institute of Physics and Technology (State University) (Russian Federation); Nechaev, S. K., E-mail: sergei.nechaev@gmail.com [Universite Paris Sud, LPTMS (France); Tamm, M. V., E-mail: thumm.m@gmail.com [Moscow State University (Russian Federation)

    2012-02-15T23:59:59.000Z

    A new statistical approach to the problem of pairwise alignment of RNA sequences is proposed. The problem is analyzed for a pair of interacting polymers forming an RNA-like hierarchical cloverleaf structures. An alignment is characterized by the numbers of matches, mismatches, and gaps. A weight function is assigned to each alignment; this function is interpreted as a free energy taking into account both direct monomer-monomer interactions and a combinatorial contribution due to formation of various cloverleaf secondary structures. The binding free energy is determined for a pair of RNA molecules. Statistical properties are discussed, including fluctuations of the binding energy between a pair of RNA molecules and loop length distribution in a complex. Based on an analysis of the free energy per nucleotide pair complexes of random RNAs as a function of the number of nucleotide types c, a hypothesis is put forward about the exclusivity of the alphabet c = 4 used by nature.

  10. Structure-Based Inhibitor Design for an Enzyme That Binds Different Steriods

    SciTech Connect (OSTI)

    Qiu,W.; Zhou, M.; Mazumdar, M.; Azzi, A.; Ghanmi, D.; Luu-The, V.; Labrie, F.; Lin, S.

    2007-01-01T23:59:59.000Z

    Human type 5 17{beta}-hydroxysteroid dehydrogenase plays a crucial role in local androgen formation in prostate tissue. Several chemicals were synthesized and tested for their ability to inhibit this enzyme, and a series of estradiol derivatives bearing a lactone on the D-ring were found to inhibit its activity efficiently. The crystal structure of the type 5 enzyme in complex with NADP and such a novel inhibitor, EM1404, was determined to a resolution of 1.30 {angstrom}. Significantly more hydrogen bonding and hydrophobic interactions were defined between EM1404 and the enzyme than in the substrate ternary complex. The lactone ring of EM1404 accounts for important interactions with the enzyme, whereas the amide group at the opposite end of the inhibitor contributes to the stability of three protein loops involved in the construction of the substrate binding site. EM1404 has a strong competitive inhibition, with a K{sub i} of 6.9 {+-} 1.4 nM, demonstrating 40 times higher affinity than that of the best inhibitor previously reported. This is observed despite the fact that the inhibitor occupies only part of the binding cavity. Attempts to soak the inhibitor into crystals of the binary complex with NADP were unsuccessful, yielding a structure with a polyethylene glycol fragment occupying the substrate binding site. The relative crystal packing is discussed. Combined studies of small molecule inhibitor synthesis, x-ray crystallography, enzyme inhibition, and molecular modeling make it possible to analyze the plasticity of the substrate binding site of the enzyme, which is essential for developing more potent and specific inhibitors for hormone-dependent cancer therapy.

  11. Ligand binding proteins: roles in ligand transfer and activation of nuclear receptors

    E-Print Network [OSTI]

    Petrescu, Anca Daniela

    2004-09-30T23:59:59.000Z

    functions: steroidogenic acute regulatory protein (StAR), hepatocyte nuclear factor-4alpha (HNF-4alpha) and acyl-CoA binding protein (ACBP). First, StAR mediates delivery of cholesterol to inner mitochondrial membrane in steroidogenesis by a poorly... structure. Fluorescent sterol exchange assays between donor and acceptor mitochondrial membranes indicate that StAR significantly increased the formation of rapidly transferable cholesterol domains. Second, HNF-4alpha, a nuclear receptor, had been shown...

  12. proteinsSTRUCTURE O FUNCTION O BIOINFORMATICS Thermodynamics of calmodulin binding to

    E-Print Network [OSTI]

    Dokholyan, Nikolay V.

    and skeletal muscle ryanodine receptor ion channels Gerhard Meissner,* Daniel A. Pasek, Naohiro Yamaguchi . A no- table property of the RyRs is that they interact with both the Ca21 -free (apoCaM) and Ca21 to the intact receptors indi- cates that the RyRs have a single, high-affinity binding domain for apoCaM and Ca

  13. Identification and functional characterization of lipid binding proteins in liver and adipose tissues of Gallus domesticus

    E-Print Network [OSTI]

    Sams, Gretchen Hubler

    1990-01-01T23:59:59.000Z

    acid binding proteins (FABPs) have been identified in a number of species. These low molecular weight proteins (12-14 kDa) demonstrate an affinity for long chain polyunsaturated fatty acids and appear to function in the metabolism of fatty acids. A... structurally distinct low molecular weight lipid transport protein, non- specific lipid transfer protein (ns-LTP), involved in cholesterol biosynthesis and metabolism, has also been identified in several species. These studies were conducted to isolate...

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

    E-Print Network [OSTI]

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

    2010-03-16T23:59:59.000Z

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

  15. The use of binding arbitration for Arizona's public works disputes as viewed from the contractor's perspective

    E-Print Network [OSTI]

    Bluff, Michael Robert

    1989-01-01T23:59:59.000Z

    works projects are derived from several sources. The purpose of this section is to review these sources and explain how they are used to deal with contract claims. The basic source of statutory procedures for filing claims against a public body... wastewater treatment plant for a county in Southern Arizona. During the course of the project, certain disputes arose between the contractor and county over amounts owed under the contract. The prime contract contained a binding arbitration clause...

  16. The Binding of Abraham: Inverting the Akedah in Fail-Safe and WarGames

    E-Print Network [OSTI]

    Dukes, Hunter B.

    2015-04-01T23:59:59.000Z

    potential Cold War scenarios: chess, 15 Dukes: The Binding of Abraham: Inverting the Akedah Published by DigitalCommons@UNO, 2015 checkers, backgammon, and Global Thermonuclear War. After beginning a game of GTW from his bedrooma game which shows up... behind JOSHUAs thinking is the satirized logic of Herman Kahn, RANDs controversial game theorist and the author of On Thermonuclear War (1960). Kahn, who calmly theorized about tragic but distinguishable postwar states and if there was any...

  17. Calculating the contribution of different binding modes to Quinacrine - DNA complex formation from polarized fluorescence data

    E-Print Network [OSTI]

    Voloshin, Igor; Karachevtsev, Victor; Zozulya, Victor

    2013-01-01T23:59:59.000Z

    Binding of acridine derivative quinacrine (QA) to chicken erythrocyte DNA was studied by methods of absorption and polarized fluorescent spectroscopy. Measurements were carried out in aqueous buffered solutions (pH 6.9) of different dye concentrations (QA concentration range from $10^{-6}$ till $10^{-4}$ M) and ionic strengths ($Na^{+}$ concentration rang from $10^{-3}$ till 0.15 M) in a wide range of phosphate-to-dye molar ratios ($P/D$). It is established that the minimum of fluorescent titration curve plotted as relative fluorescence intensity $vs$ $P/D$ is conditioned by the competition between the two types of QA binding to DNA which posses by different emission parameters: (i) intercalative one dominating under high $P/D$ values, and (ii) outside electrostatic binding dominating under low $P/D$ values, which is accompanied by the formation of non-fluorescent dye associates on the DNA backbone. Absorption and fluorescent characteristics of complexes formed were determined. The method of calculation of di...

  18. Protein-salt binding data from potentiometric titrations of lysozyme in aqueous solutions containing KCl

    SciTech Connect (OSTI)

    Engmann, J.; Blanch, H.W.; Prausnitz, J.M. [Univ. of California, Berkeley, CA (United States). Dept. of Chemical Engineering]|[Lawrence Berkeley National Lab., CA (United States). Chemical Sciences Div.

    1997-03-01T23:59:59.000Z

    An existing method for potentiometric titrations of proteins was improved, tested and applied to titrations of the enzyme hen-egg-white lysozyme in aqueous solutions containing KCl at ionic strengths from 0.1 M to 2.0 M at 25 C. Information about the protein`s net charge dependence on pH and ionic strength were obtained and salt binding numbers for the system were calculated using a linkage concept. For the pH range 2.5--11.5, the net charge slightly but distinctly increases with increasing ionic strength between 0.1 M and 2.0 M. The differences are most distinct in the pH region below 5. Above pH 11.35, the net charge decreases with increasing ionic strength. Preliminary calculation of binding numbers from titration curves at 0.1 M and 1.0 M showed selective association of chloride anions and expulsion of potassium ions at low pH. Ion-binding numbers from this work will be used to evaluate thermodynamic properties and to correlate crystallization or precipitation phase-equilibrium data in terms of a model based on the integral-equation theory of fluids which is currently under development.

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

    SciTech Connect (OSTI)

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

    2012-08-24T23:59:59.000Z

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

  20. Binding Energies and Radii of the Nuclei with N >=Z in an Alpha-Cluster Model

    E-Print Network [OSTI]

    G. K. Nie

    2008-07-01T23:59:59.000Z

    Using the surface tension energy put in dependence on the number of alpha-clusters in the core in a phenomenological model representing a nucleus as a core and a nuclear molecule on its surface leads to widening the number of isotopes to be described from the narrow strip of beta-stability to the isotopes with N >= Z. The number of alpha-clusters in the molecule is obtained from the analysis of experimental binding energies and the specific density of the core binding energy \\rho and the radii are calculated. It is shown that for the isotopes of one Z with growing A the number of alpha-clusters of the molecule decreases mostly to 3 and \\rho increases to reach a saturation value within \\rho = 2.5 \\div 2.7 MeV/fm^3 at the beta - stable isotopes, so the narrow strip of the binding energies of the beta - stable isotopes with Z <= 84 is outlined by a function of one variable Z.

  1. 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 (Queens)

    2012-08-01T23:59:59.000Z

    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.

  2. 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 Aging Research, Guangdong Medical College, Dongguan 523808 (China) [Institute of Aging Research, Guangdong Medical College, Dongguan 523808 (China); Institute of Biochemistry and Molecular Biology, Guangdong Medical College, Zhanjiang 524023 (China); Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Dongguan 523808 (China); Zhou, Zhongjun [Institute of Aging Research, Guangdong Medical College, Dongguan 523808 (China) [Institute of Aging Research, Guangdong Medical College, Dongguan 523808 (China); Department of Biochemistry, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong (China); Liu, Xinguang, E-mail: xgliu64@126.com [Institute of Aging Research, Guangdong Medical College, Dongguan 523808 (China) [Institute of Aging Research, Guangdong Medical College, Dongguan 523808 (China); Institute of Biochemistry and Molecular Biology, Guangdong Medical College, Zhanjiang 524023 (China); Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Dongguan 523808 (China)

    2013-10-11T23:59:59.000Z

    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.

  3. Biological activities of binding site specific monoclonal antibodies to prolactin receptors of rabbit mammary gland

    SciTech Connect (OSTI)

    Djiane, J.; Dusanter-Fourt, I.; Katoh, M.; Kelly, P.A.

    1985-09-25T23:59:59.000Z

    The biological activity of three monoclonal antibodies (mAbs) against the rabbit mammary prolactin (PRL) receptor (M110, A82, and A917) were investigated using explants of rabbit mammary gland. The three mAbs which were all able to inhibit the binding of SVI-ovine prolactin to its receptor had different biological activities. Two mAbs (M110 and A82) were able to prevent the stimulating effect of PRL on casein synthesis when the molar ratio between the mAb and PRL was 100. One mAb (A917) was able to mimic the action of PRL on both casein and DNA ((TH)thymidine incorporation) synthesis, whereas the other two mAbs were without any stimulatory effect. For this stimulatory effect to be observed, bivalency of the antibody was essential, since monovalent fragments, which were able to inhibit PRL binding, had no agonistic activity. The ability of the mAbs to induce a down-regulation of receptors was also studied. These studies suggest that the binding domain of the receptor might be relatively complex, since only a part of this domain recognized by the antibody with PRL-like activity was able to induce hormonal action. Alternatively, only those antibodies able to microaggregate the receptors may possess PRL-like activity.

  4. Structural aspects of catalytic mechanisms of endonucleases and their binding to nucleic acids

    SciTech Connect (OSTI)

    Zhukhlistova, N. E.; Balaev, V. V.; Lyashenko, A. V.; Lashkov, A. A., E-mail: alashkov83@gmail.com [Russian Academy of Sciences, Shubnikov Institute of Crystallography (Russian Federation)

    2012-05-15T23:59:59.000Z

    Endonucleases (EC 3.1) are enzymes of the hydrolase class that catalyze the hydrolytic cleavage of deoxyribonucleic and ribonucleic acids at any region of the polynucleotide chain. Endonucleases are widely used both in biotechnological processes and in veterinary medicine as antiviral agents. Medical applications of endonucleases in human cancer therapy hold promise. The results of X-ray diffraction studies of the spatial organization of endonucleases and their complexes and the mechanism of their action are analyzed and generalized. An analysis of the structural studies of this class of enzymes showed that the specific binding of enzymes to nucleic acids is characterized by interactions with nitrogen bases and the nucleotide backbone, whereas the nonspecific binding of enzymes is generally characterized by interactions only with the nucleic-acid backbone. It should be taken into account that the specificity can be modulated by metal ions and certain low-molecular-weight organic compounds. To test the hypotheses about specific and nonspecific nucleic-acid-binding proteins, it is necessary to perform additional studies of atomic-resolution three-dimensional structures of enzyme-nucleic-acid complexes by methods of structural biology.

  5. A Single-Domain Llama Antibody Potently Inhibits the Enzymatic Activity of Botulinum Neurotoxin by Binding to the Non-Catalytic [alpha]-Exosite Binding Region

    SciTech Connect (OSTI)

    Dong, Jianbo; Thompson, Aaron A.; Fan, Yongfeng; Lou, Jianlong; Conrad, Fraser; Ho, Mengfei; Pires-Alves, Melissa; Wilson, Brenda A.; Stevens, Raymond C.; Marks, James D. (UIUC); (Scripps); (UCSF)

    2010-08-13T23:59:59.000Z

    Ingestion or inhalation of botulinum neurotoxin (BoNT) results in botulism, a severe and frequently fatal disease. Current treatments rely on antitoxins, which, while effective, cannot reverse symptoms once BoNT has entered the neuron. For treatments that can reverse intoxication, interest has focused on developing inhibitors of the enzymatic BoNT light chain (BoNT Lc). Such inhibitors typically mimic substrate and bind in or around the substrate cleavage pocket. To explore the full range of binding sites for serotype A light chain (BoNT/A Lc) inhibitors, we created a library of non-immune llama single-domain VHH (camelid heavy-chain variable region derived from heavy-chain-only antibody) antibodies displayed on the surface of the yeast Saccharomyces cerevisiae. Library selection on BoNT/A Lc yielded 15 yeast-displayed VHH with equilibrium dissociation constants (K{sub d}) from 230 to 0.03 nM measured by flow cytometry. Eight of 15 VHH inhibited the cleavage of substrate SNAP25 (synaptosome-associated protein of 25,000 Da) by BoNT/A Lc. The most potent VHH (Aa1) had a solution K{sub d} for BoNT/A Lc of 1.47 x 10{sup -10} M and an IC{sub 50} (50% inhibitory concentration) of 4.7 x 10{sup -10} M and was resistant to heat denaturation and reducing conditions. To understand the mechanism by which Aa1 inhibited catalysis, we solved the X-ray crystal structure of the BoNT/A Lc-Aa1 VHH complex at 2.6 {angstrom} resolution. The structure reveals that the Aa1 VHH binds in the {alpha}-exosite of the BoNT/A Lc, far from the active site for catalysis. The study validates the utility of non-immune llama VHH libraries as a source of enzyme inhibitors and identifies the BoNT/A Lc {alpha}-exosite as a target for inhibitor development.

  6. Binding energy of (Lambda)He-7 and test of charge symmetry breaking in the Lambda N interaction potential

    SciTech Connect (OSTI)

    Hashimoto, O; Honda, D; Kaneta, M; Kato, F; Kawama, D; Maruyama, N; Matsumura, A; Nakamura, S N; Nomura, H; Nonaka, K; Ohtani, A; Okayasu, Y; Osaka, M; Oyamada, M; Sumihama, M; Tamura, H; Baker, O K; Cole, L; Christy, M; Gueye, P; Keppel, C; Tang, L; Yuan, L; Acha, A; Baturin, P; Boeglin, W; Kramer, L; Markowitz, P; Pamela, P; Perez, N; Raue, B; Reinhold, J; Rivera, R; Kato, S; Sato, Y; Takahashi, T; Daniel, A; Hungerford, Ed V; Ispiryan, M; Kalantarians, N; Lan, K J; Li, Y; Miyoshi, T; Randeniya, S; Rodriguez, V M; Bosted, P; Carlini, R; Ent, R; Fenker, H; Gaskell, D; Jones, M; Mack, D; Roche, J; Smith, G; Tvaskis, V; Vulcan, W; Wood, S; Yan, C; Asaturyan, A; Asaturyan, R; Egiyan, K; Mkrtchyan, H; Margaryan, A; Navasardyan, T; Tadevosyan, V; Zamkochian, S; Hu, B; Song, Y; Luo, W; Androic, D; Furic, M; Petkovic, T; Seva, T; Ahmidouch, A; Danagoulian, S; Gasparian, A; Halkyard, R; Johnson, K; Simicevic, N; Wells, S; Niculescu, G; Niculescu, M I; Gan, L; Benmokhtar, F; Horn, T; Elassar, M

    2011-09-01T23:59:59.000Z

    The binding energy of 7LambdaHe has been obtained for the first time with reaction spectroscopy using the (e, e'K+) reaction at Jefferson Lab's Hall C. A comparison among the binding energies of the A = 7 T = l iso-triplet hypernuclei, 7LambdaHe, 7LambdaLi*and 7LambdaBe, is made and possible charge symmetry breaking (CSB) in the LambdaN potential is discussed. For 7LambdaHe and 7LambdaBe, the shifts in binding energies are opposite to those predicted by a recent cluster model calculation, which assumes that the unexplained part of the binding energy difference between 4LambdaH and 4LambdaHe, is due to the CSB of the LambdaN potential. Further examination of CSB in light hypernuclear systems is required both experimentally and theoretically.

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

    E-Print Network [OSTI]

    Jean-Marie Barbaroux; Semjon Vugalter

    2013-06-19T23:59:59.000Z

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

  8. X-ray diffraction study of the binding of the antisickling agent 12C79 to human hemoglobin

    SciTech Connect (OSTI)

    Wireko, R.C.; Abraham, D.J. (Virginia Commonwealth Univ., Richmond (United States))

    1991-03-15T23:59:59.000Z

    The hemoglobin binding site of the antisickling agent 12C79 has been determined by x-ray crystallography. 12C79 is recognized as one of the first molecules to reach clinical trials that was designed, de novo, from x-ray-determined atomic coordinates of a protein. Several previous attempts to verify the proposed Hb binding sites via crystallographic studies have failed. Using revised experimental procedures, the authors obtained 12C79-deoxhemoglobin crystals grown after reaction with oxyhemoglobin and cyanoborohydride reduction to stabilize the Schiff base linkage. The difference electron-density Fourier maps show that two 12C79 molecules bind covalently to both symmetry-related N-terminal amino groups of the hemoglobin {alpha} chains. This is in contrast to the original design that proposed the binding of one drug molecule that spans the molecular dyad to interact with both N-terminal {alpha}-amino groups.

  9. Networks link antigenic and receptor-binding sites of influenza hemagglutinin: Mechanistic insight into fitter strain propagation

    E-Print Network [OSTI]

    Soundararajan, Venkataramanan

    Influenza viral passaging through pre-vaccinated mice shows that emergent antigenic site mutations on the viral hemagglutinin (HA) impact host receptor-binding affinity and, therefore, the evolution of fitter influenza ...

  10. Brief Articles A Swift All-Atom Energy-Based Computational Protocol to Predict DNA-Ligand Binding

    E-Print Network [OSTI]

    Jayaram, Bhyravabotla

    atomic charges on the DNA and ligand atoms calculated from Coulomb's law, employing a sigmoidal dielecBrief Articles A Swift All-Atom Energy-Based Computational Protocol to Predict DNA-Ligand Binding

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

    E-Print Network [OSTI]

    Gordan, Raluca

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

  12. 1Lesions in the mRNA cap-binding gene ABA HYPERSENSITIVE 1 suppress FRIGIDA-mediated delayed

    E-Print Network [OSTI]

    Raines, Ronald T.

    1Lesions in the mRNA cap-binding gene ABA HYPERSENSITIVE 1 suppress FRIGIDA-mediated delayed morphology were identified in T-DNA and fast-neutron mutant populations. Molecular analysis showed

  13. Cytotoxicity of 1,2-epoxynaphthalene Is Correlated with Protein Binding and in Situ Glutathione Depletion in Cytochrome

    E-Print Network [OSTI]

    Hammock, Bruce D.

    refinery streams and coal tar feedstocks produce hundreds of millions of pounds annually (Kirk and Othmer to bind covalently to nu- cleophilic amino acid residues of cellular proteins and thus cause cytotoxicity

  14. S.IM.PL Serialization: Type System Scopes Encapsulate Cross-Language, Multi-Format Information Binding

    E-Print Network [OSTI]

    Shahzad, Nabeel

    2012-02-14T23:59:59.000Z

    repetitive, tedious code to map loosely-typed serialized data to strongly-typed program objects. We developed S.IM.PL Serialization, a cross-language multi-format information binding framework to relieve developers from the burdens associated...

  15. 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)

    1984-04-24T23:59:59.000Z

    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.

  16. Crystal Structures of the Staphylococcal Toxin SSL5 in Complex With Sialyl-Lewis X Reveal a Conserved Binding Site That Shares Common Features With Viral And Bacterial Sialic Acid-Binding Proteins

    SciTech Connect (OSTI)

    Baker, H.M.; Basu, I.; Chung, M.C.; Caradoc-Davies, T.; Fraser, J.D.; Baker, E.N.

    2009-06-02T23:59:59.000Z

    Staphylococcus aureus is a significant human pathogen. Among its large repertoire of secreted toxins is a group of staphylococcal superantigen-like proteins (SSLs). These are homologous to superantigens but do not have the same activity. SSL5 is shown here to bind to human granulocytes and to the cell surface receptors for human IgA (Fc alphaRI) and P-selectin [P-selectin glycoprotein ligand-1 (PSGL-1)] in a sialic acid (Sia)-dependent manner. Co-crystallization of SSL5 with the tetrasaccharide sialyl Lewis X (sLe(X)), a key determinant of PSGL-1 binding to P-selectin, led to crystal structures of the SSL5-sLe(X) complex at resolutions of 1.65 and 2.75 A for crystals at two pH values. In both structures, sLe(X) bound to a specific site on the surface of the C-terminal domain of SSL5 in a conformation identical with that bound by P-selectin. Conservation of the key carbohydrate binding residues indicates that this ability to bind human glycans is shared by a substantial subgroup of the SSLs, including SSL2, SSL3, SSL4, SSL5, SSL6, and SSL11. This indicates that the ability to target human glycans is an important property of this group of toxins. Structural comparisons also showed that the Sia binding site in SSL5 contains a substructure that is shared by other Sia binding proteins from bacteria as well as viruses and represents a common binding motif.

  17. Detection Of Amplified Or Deleted Chromosomal Regions

    DOE Patents [OSTI]

    Stokke, Trond (San Fransisco, CA), Pinkel, Daniel (Walnut Creek, CA), Gray, Joe W. (San Fransisco, CA)

    1997-05-27T23:59:59.000Z

    The present invention relates to in situ hybridization methods for the identification of new chromosomal abnormalities associated with various diseases. In particular, it provides probes which are specific to a region of amplification in chromosome 20.

  18. Detection of amplified or deleted chromosomal regions

    DOE Patents [OSTI]

    Stokke, Trond (San Francisco, CA); Pinkel, Daniel (Walnut Creek, CA); Gray, Joe W. (San Francisco, CA)

    1995-01-01T23:59:59.000Z

    The present invention relates to in situ hybridization methods for the identification of new chromosomal abnormalities associated with various diseases. In particular, it provides probes which are specific to a region of amplification in chromosome 20.

  19. Help:Deleting pages | Open Energy Information

    Open Energy Info (EERE)

    AFDC Printable Version Share this resource Send a link to EERE: Alternative Fuels Data Center Home Page to someone by E-mail Share EERE: Alternative Fuels Data Center Home Page on Facebook Tweet about EERE: Alternative Fuels Data Center Home Page on Twitter Bookmark EERE: Alternative Fuels Data Center Home Page onYou are now leaving Energy.gov You are now leaving Energy.gov You are being directedAnnual Siteof Energy 2,AUDIT REPORTEnergyFarms AHefei Sungrow Power SupplyProviding CitationsSee

  20. Category:Proposed deletion | Open Energy Information

    Open Energy Info (EERE)

    AFDC Printable Version Share this resource Send a link to EERE: Alternative Fuels Data Center Home Page to someone by E-mail Share EERE: Alternative Fuels Data Center Home Page on Facebook Tweet about EERE: Alternative Fuels Data Center Home Page on Twitter Bookmark EERE: Alternative Fuels Data Center Home Page onYou are now leaving Energy.gov You are now leaving Energy.gov You are being directedAnnual Siteof EnergyInnovation inOpen EnergyCallawayCaparaAcademicBoard

  1. PartialDeletion for web.cdr

    Office of Legacy Management (LM)

    AFDC Printable Version Share this resource Send a link to EERE: Alternative Fuels Data Center Home Page to someone by E-mail Share EERE: Alternative Fuels Data Center Home Page on Facebook Tweet about EERE: Alternative Fuels Data Center Home Page on Twitter Bookmark EERE: Alternative1 First Use of Energy for All Purposes (Fuel and Nonfuel), 2002; Level: National5Sales for4,645 3,625 1,006 492 742EnergyOn AprilA groupTuba City, Arizona, DisposalFourthN V O 1 8 7 +NewAugust 4,P -.,.States

  2. RNA-binding properties and RNA chaperone activity of human peroxiredoxin 1

    SciTech Connect (OSTI)

    Kim, Ji-Hee; Lee, Jeong-Mi; Lee, Hae Na; Kim, Eun-Kyung; Ha, Bin [Lee Gil Ya Cancer and Diabetes Institute, Gachon University (Korea, Republic of)] [Lee Gil Ya Cancer and Diabetes Institute, Gachon University (Korea, Republic of); Ahn, Sung-Min, E-mail: smahn@gachon.ac.kr [Lee Gil Ya Cancer and Diabetes Institute, Gachon University (Korea, Republic of) [Lee Gil Ya Cancer and Diabetes Institute, Gachon University (Korea, Republic of); Department of Translational Medicine, Gachon University Gil Hospital, Incheon (Korea, Republic of); Jang, Ho Hee, E-mail: hhjang@gachon.ac.kr [Lee Gil Ya Cancer and Diabetes Institute, Gachon University (Korea, Republic of); Lee, Sang Yeol [Division of Applied Life Sciences (Brain Korea 21 program), Gyeongsang National University, Jinju 660-701 (Korea, Republic of)] [Division of Applied Life Sciences (Brain Korea 21 program), Gyeongsang National University, Jinju 660-701 (Korea, Republic of)

    2012-09-07T23:59:59.000Z

    Highlights: Black-Right-Pointing-Pointer hPrx1 has RNA-binding properties. Black-Right-Pointing-Pointer hPrx1 exhibits helix-destabilizing activity. Black-Right-Pointing-Pointer Cold stress increases hPrx1 level in the nuclear fraction. Black-Right-Pointing-Pointer hPrx1 enhances the viability of cells exposed to cold stress. -- Abstract: Human peroxiredoxin 1 (hPrx1), a member of the peroxiredoxin family, detoxifies peroxide substrates and has been implicated in numerous biological processes, including cell growth, proliferation, differentiation, apoptosis, and redox signaling. To date, Prx1 has not been implicated in RNA metabolism. Here, we investigated the ability of hPrx1 to bind RNA and act as an RNA chaperone. In vitro, hPrx1 bound to RNA and DNA, and unwound nucleic acid duplexes. hPrx1 also acted as a transcription anti-terminator in an assay using an Escherichia coli strain containing a stem-loop structure upstream of the chloramphenicol resistance gene. The overall cellular level of hPrx1 expression was not increased at low temperatures, but the nuclear level of hPrx1 was increased. In addition, hPrx1 overexpression enhanced the survival of cells exposed to cold stress, whereas hPrx1 knockdown significantly reduced cell survival under the same conditions. These findings suggest that hPrx1 may perform biological functions as a RNA-binding protein, which are distinctive from known functions of hPrx1 as a reactive oxygen species scavenger.

  3. Structural Basis for Nucleotide Binding and Reaction Catalysis in Mevalonate Diphosphate Decarboxylase

    SciTech Connect (OSTI)

    Barta, Michael L.; McWhorter, William J.; Miziorko, Henry M.; Geisbrecht, Brian V. (UMKC)

    2012-09-17T23:59:59.000Z

    Mevalonate diphosphate decarboxylase (MDD) catalyzes the final step of the mevalonate pathway, the Mg{sup 2+}-ATP dependent decarboxylation of mevalonate 5-diphosphate (MVAPP), producing isopentenyl diphosphate (IPP). Synthesis of IPP, an isoprenoid precursor molecule that is a critical intermediate in peptidoglycan and polyisoprenoid biosynthesis, is essential in Gram-positive bacteria (e.g., Staphylococcus, Streptococcus, and Enterococcus spp.), and thus the enzymes of the mevalonate pathway are ideal antimicrobial targets. MDD belongs to the GHMP superfamily of metabolite kinases that have been extensively studied for the past 50 years, yet the crystallization of GHMP kinase ternary complexes has proven to be difficult. To further our understanding of the catalytic mechanism of GHMP kinases with the purpose of developing broad spectrum antimicrobial agents that target the substrate and nucleotide binding sites, we report the crystal structures of wild-type and mutant (S192A and D283A) ternary complexes of Staphylococcus epidermidis MDD. Comparison of apo, MVAPP-bound, and ternary complex wild-type MDD provides structural information about the mode of substrate binding and the catalytic mechanism. Structural characterization of ternary complexes of catalytically deficient MDD S192A and D283A (k{sub cat} decreased 10{sup 3}- and 10{sup 5}-fold, respectively) provides insight into MDD function. The carboxylate side chain of invariant Asp{sup 283} functions as a catalytic base and is essential for the proper orientation of the MVAPP C3-hydroxyl group within the active site funnel. Several MDD amino acids within the conserved phosphate binding loop ('P-loop') provide key interactions, stabilizing the nucleotide triphosphoryl moiety. The crystal structures presented here provide a useful foundation for structure-based drug design.

  4. Binding Effects in High-Energy Scattering Applied to K-Shell Ionization

    E-Print Network [OSTI]

    Binstock, J.; Reading, John F.

    1975-01-01T23:59:59.000Z

    PHYSICA L RE VIEW A VOLUME 11, NUMBER APRIL 1975 Binding effects in high-energy scattering applied to K-shell ionization* J. Binstock and J. F. Reading Physics Department and Cyclotron Institute, Texas ASM University, College Station, Texas 77843... (Received 30 October 1974) The equation describing scattering of a fast ion by a E-shell electron, ihv 881/BZ = exp (iHe Z/k ) V(r, R) exp (-sHeZ/h v) S? where He ( ) =- {0 /2~ e)+ r ?(@ /~e) l8 1n Xo (&)/~&~ 8/8&:?FT+ BT, is solved in the Glauber...

  5. 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

  6. Radii and Binding Energies of Nuclei in the Alpha-Cluster Model

    E-Print Network [OSTI]

    G. K. Nie

    2006-03-22T23:59:59.000Z

    The alpha-cluster model is based on two assumptions that the proton-neutron pair interactions are responsible for adherence between alpha-clusters and that the NN-interaction in the alpha-clusters is isospin independent. It allows one to estimate the Coulomb energy and the short range inter-cluster bond energy in dependence on the number of clusters. The charge radii are calculated on the number of alpha-clusters too. Unlike the Weizsacker formula in this model the binding energies of alpha-clusters and excess neutrons are estimated separately. The calculated values are in a good agreement with the experimental data.

  7. CO2>Binding)Organic)Liquids)Gas)Capture)with) Polarity>Swing>Assisted)Regeneration)

    SciTech Connect (OSTI)

    Heldebrant, David

    2014-05-31T23:59:59.000Z

    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.

  8. Odd-even staggering in nuclear binding and the liquid-drop model

    E-Print Network [OSTI]

    W. A. Friedman

    2009-11-03T23:59:59.000Z

    The trends with mass number are examined for the odd-even-staggering (OES) in nuclear binding of neutrons and protons through the conventional measures $\\Delta^{(3)}$. The large differences previously observed between these trends for even and odd values of these measures is found to arise, in part, from the slow variation of binding energies with mass and charge which provides a background contribution. This background is estimated with the liquid-drop model, and accounts for the greater difference found in proton removal relative to neutron removal. The differences which persist after backgrounds are removed can not be treated in the conventional liquid-drop model but require the addition of a new term. Such a term is investigated, and its effect on specific values of the OES is calcutated. The liquid-drop fitting is also applied to a set of separation energies constrained to match the specific set of nuclei used to determine the observed values for the odd $\\Delta^{(3)}$. The resulting fit for the pairing term is compared to the average value of even and odd measures. The effect on this value of the new liquid-drop term is observed, and the change in background when the new term is included is also used as an alternate method for determining the difference between trends of the even and odd values of the OES.

  9. Many-Body Dispersion Effects in the Binding of Adsorbates on Metal Surfaces

    E-Print Network [OSTI]

    Maurer, Reinhard J; Tkatchenko, Alexandre

    2015-01-01T23:59:59.000Z

    A correct description of electronic exchange and correlation effects for molecules in contact with extended (metal) surfaces is a challenging task for first-principles modeling. In this work we demonstrate the importance of collective van der Waals dispersion effects beyond the pairwise approximation for organic--inorganic systems on the example of atoms, molecules, and nanostructures adsorbed on metals. We use the recently developed many-body dispersion (MBD) approach in the context of density-functional theory [Phys. Rev. Lett. 108, 236402 (2012); J. Chem. Phys. 140, 18A508 (2014)] and assess its ability to correctly describe the binding of adsorbates on metal surfaces. We briefly review the MBD method and highlight its similarities to quantum-chemical approaches to electron correlation in a quasiparticle picture. In particular, we study the binding properties of xenon, 3,4,9,10-perylene-tetracarboxylic acid (PTCDA), and a graphene sheet adsorbed on the Ag(111) surface. Accounting for MBD effects we are abl...

  10. Tolerance to cadmium and cadmium-binding ligands in Great Salt Lake brine shrimp (Artemia salina)

    SciTech Connect (OSTI)

    Jayasekara, S.; Drown, D.B.; Sharma, R.P.

    1986-02-01T23:59:59.000Z

    Information on the accumulation of cadmium in cytosolic proteins of Great Lake brine shrimp (Artemia salina) was obtained from animals collected directly from the lake and also from animal hatched and maintained in three sublethal concentrations of cadmium (0.5, 2.0, 5.0 ppm) in saltwater aquaria. Brine shrimp growth under these conditions was monitored by measuring body lengths during a 7-day exposure period. Heat-stable, cadmium-binding ligands were isolated and identified by Sephadex G-75 chromatography and atomic absorption spectrophotometry. Cadmium was found to be equally distributed between high and low molecular weight proteins in animals collected from the lake and the 0.5 ppm cadmium group. There was also a slight growth stimulation noted in the 0.5-pm group. Higher cadmium incorporation was noted in low molecular weight fractions with increasing cadmium concentration in the exposure media. Low molecular weight fractions were also found to have high uv absorption characteristics at 250 nm and low absorption at 280 nm. Molecular weight of the cadmium-binding ligands was found to be 11,000 as estimated by the gel filtration method. De novo synthesis of this protein was increased as a function of cadmium concentration in the media. However, slow accumulation of cadmium in other protein fractions was also noticed in higher cadmium exposure groups, suggesting the existence of possible tolerance mechanisms in brine shrimp exposed to suspected acute cadmium concentrations.

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

    SciTech Connect (OSTI)

    Hassaneen, Kh.S.A., E-mail: khs_94@yahoo.com [Physics Department, Faculty of Science, Sohag University, Sohag (Egypt); Abo-Elsebaa, H.M.; Sultan, E.A. [Physics Department, Faculty of Science, Sohag University, Sohag (Egypt); Mansour, H.M.M. [Physics Department, Faculty of Science, Cairo University, Giza (Egypt)

    2011-03-15T23:59:59.000Z

    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.

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

    SciTech Connect (OSTI)

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

    2010-09-02T23:59:59.000Z

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

  13. Control of the level of unusual estrogen-binding protein in rat liver by sex steroids and the pituitary

    SciTech Connect (OSTI)

    Smirnova, O.V.; Rozen, V.B.; Vishnyakova, T.G.

    1986-02-01T23:59:59.000Z

    This paper studies the role of sex steriods and the pituitary in regulation of the unusual estrogen-binding protein (UEBP) level in male rat liver. The concentration of E/sub 2/-binding sites of UEBP in the liver cytosol was determined by measuring binding of a minimal addition of 2,4,6,7-tritium-E/sub 2/, with specific radioactivity of 98-100 Ci/mmole. Data on the effect of hypophysectomy on the UEBP level in the liver of different groups of rats are presented. The presence of comparable quantities of E/sub 2/ and androgens in rats of both sexes is evidence of the existence of a fine mechanism of combined regulation of the UEBP concentration under natural conditions that reflect changes in the absolute E/sub 2/ or androgen levels or in the ratio between them.

  14. Addendum: Triton and hypertriton binding energies calculated from SU_6 quark-model baryon-baryon interactions

    E-Print Network [OSTI]

    Y. Fujiwara; Y. Suzuki; M. Kohno; K. Miyagawa

    2007-09-29T23:59:59.000Z

    Previously we calculated the binding energies of the triton and hypertriton, using an SU_6 quark-model interaction derived from a resonating-group method of two baryon clusters. In contrast to the previous calculations employing the energy-dependent interaction kernel, we present new results using a renormalized interaction, which is now energy independent and reserves all the two-baryon data. The new binding energies are slightly smaller than the previous values. In particular the triton binding energy turns out to be 8.14 MeV with a charge-dependence correction of the two-nucleon force, 190 keV, being included. This indicates that about 350 keV is left for the energy which is to be accounted for by three-body forces.

  15. A Conserved Surface Loop in Type I Dehydroquinate Dehydratases Positions an Active Site Arginine and Functions in Substrate Binding

    SciTech Connect (OSTI)

    Light, Samuel H.; Minasov, George; Shuvalova, Ludmilla; Peterson, Scott N.; Caffrey, Michael; Anderson, Wayne F.; Lavie, Arnon (UC); (UIC)

    2012-04-18T23:59:59.000Z

    Dehydroquinate dehydratase (DHQD) catalyzes the third step in the biosynthetic shikimate pathway. We present three crystal structures of the Salmonella enterica type I DHQD that address the functionality of a surface loop that is observed to close over the active site following substrate binding. Two wild-type structures with differing loop conformations and kinetic and structural studies of a mutant provide evidence of both direct and indirect mechanisms of involvement of the loop in substrate binding. In addition to allowing amino acid side chains to establish a direct interaction with the substrate, closure of the loop necessitates a conformational change of a key active site arginine, which in turn positions the substrate productively. The absence of DHQD in humans and its essentiality in many pathogenic bacteria make the enzyme a target for the development of nontoxic antimicrobials. The structures and ligand binding insights presented here may inform the design of novel type I DHQD inhibiting molecules.

  16. Binding-induced Stabilization and Assembly of the Phage P22 Tail Accessory Factor gp4

    SciTech Connect (OSTI)

    Olia,A.; Al-Bassam, J.; Winn-Stapley, D.; Joss, L.; Casjens, S.; Cingolani, G.

    2006-01-01T23:59:59.000Z

    To infect and replicate, bacteriophage P22 injects its 43 kbp genome across the cell wall of Salmonella enterica serovar Typhimurium. The attachment of phage P22 to the host cell as well as the injection of the viral DNA into the host is mediated by the virion's tail complex. This 2.8 MDa molecular machine is formed by five proteins, which include the portal protein gp1, the adhesion tailspike protein gp9, and three tail accessory factors: gp4, gp10, gp26. We have isolated the tail accessory factor gp4 and characterized its structure and binding interactions with portal protein. Interestingly, gp4 exists in solution as a monomer, which displays an exceedingly low structural stability (T{sub m} 34 {sup o}C). Unfolded gp4 is prone to aggregation within a narrow range of temperatures both in vitro and in Salmonella extracts. In the virion the thermal unfolding of gp4 is prevented by the interaction with the dodecameric portal protein, which stabilizes the structure of gp4 and suppresses unfolded gp4 from irreversibly aggregating in the Salmonella milieu. The structural stabilization of gp4 is accompanied by the concomitant oligomerization of the protein to form a ring of 12 subunits bound to the lower end of the portal ring. The interaction of gp4 with portal protein is complex and likely involves the distinct binding of two non-equivalent sets of six gp4 proteins. Binding of the first set of six gp4 equivalents to dodecameric portal protein yields a gp(1){sub 12}:gp(4){sub 6} assembly intermediate, which is stably populated at 30 {sup o}C and can be resolved by native gel electrophoresis. The final product of the assembly reaction is a bi-dodecameric gp(1){sub 12}:gp(4){sub 12} complex, which appears hollow by electron microscopy, suggesting that gp4 does not physically plug the DNA entry/exit channel, but acts as a structural adaptor for the other tail accessory factors: gp10 and gp26.

  17. 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.

    2008-01-10T23:59:59.000Z

    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.

  18. Binding Energetics of Substitutional and Interstitial Helium and Di-Helium Defects with Grain Boundary Structure in alpha-Fe

    SciTech Connect (OSTI)

    Tschopp, Mark A.; Gao, Fei; Yang, Li; Solanki, K. N.

    2014-01-21T23:59:59.000Z

    he formation/binding energetics and length scales associated with the interaction between He atoms and grain boundaries in BCC alpha-Fe was explored. Ten different low grain boundaries from the <100> and <110> symmetric tilt sigma grain boundary systems were used. In this work, we then calculated formation/binding energies for 1 - 2 He atoms in the substitutional and interstitial sites (HeV, He2V, HeInt, He2Int) at all potential grain boundary sites within 15 A of the boundary (52826 simulations total). The present results provide detailed information about the interaction energies and length scales of 1-2 He atoms with grain boundaries for the structures examined. A number of interesting new findings emerge from the present study. For instance, the sigma3(112) twin boundary in BCC Fe possesses a much smaller binding energy than other boundaries, which corresponds in long time dynamics simulations to the ability of an interstitial He defect to break away from the boundary in simulations on the order of nanoseconds. Additionally, positive correlations between the calculated formation/binding energies of the He defects (R > 0.9) asserts that the local environment surrounding each site strongly influences the He defect energies and that highly accurate quantum mechanics calculations of lower order defects may be an adequate predictor of higher order defects. Various metrics to quantify or classify the local environment were compared with the He defect binding energies. The present work shows that the binding and formation energies for He defects are important for understanding the physics of He diffusion and trapping by grain boundaries, which can be important for modeling He interactions in polycrystalline steels.

  19. Binding energetics of substitutional and interstitial helium and di-helium defects with grain boundary structure in ?-Fe

    SciTech Connect (OSTI)

    Tschopp, M. A., E-mail: mark.tschopp@gatech.edu [Dynamic Research Corporation, (on site at) U.S. Army Research Laboratory, Aberdeen Proving Ground, Maryland 21005 (United States); Center for Advanced Vehicular Systems, Mississippi State University, Starkville, Mississippi 39762 (United States); Gao, F.; Yang, L. [Pacific Northwest National Laboratory, Richland, Washington 99352 (United States); Solanki, K. N. [Arizona State University, School for Engineering of Matter, Transport and Energy, Tempe, Arizona 85287 (United States)

    2014-01-21T23:59:59.000Z

    The formation/binding energetics and length scales associated with the interaction between He atoms and grain boundaries in BCC ?-Fe were explored. Ten different low ? grain boundaries from the ?100? and ?110? symmetric tilt grain boundary systems were used. In this work, we then calculated formation/binding energies for 12 He atoms in the substitutional and interstitial sites (HeV, He{sub 2}V, HeInt, He{sub 2}Int) at all potential grain boundary sites within 15? of the boundary (52?826 simulations total). The present results provide detailed information about the interaction energies and length scales of 12 He atoms with grain boundaries for the structures examined. A number of interesting new findings emerge from the present study. For instance, the ?3(112) twin boundary in BCC Fe possesses a much smaller binding energy than other boundaries, which corresponds in long time dynamics simulations to the ability of an interstitial He defect to break away from the boundary in simulations on the order of nanoseconds. Additionally, positive correlations between the calculated formation/binding energies of the He defects (R?>?0.9) asserts that the local environment surrounding each site strongly influences the He defect energies and that highly accurate quantum mechanics calculations of lower order defects may be an adequate predictor of higher order defects. Various metrics to quantify or classify the local environment were compared with the He defect binding energies. The present work shows that the binding and formation energies for He defects are important for understanding the physics of He diffusion and trapping by grain boundaries, which can be important for modeling He interactions in polycrystalline steels.

  20. 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. (MIT); (UT-Australia); (Macquarie); (Toronto); (New South)

    2012-02-15T23:59:59.000Z

    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.

  1. Full $0\\hbar?$ shell model calculation of the binding energies of the $1f_{7/2}$ nuclei

    E-Print Network [OSTI]

    E. Caurier; G. Martinez-Pinedo; F. Nowacki; A. Poves; J. Retamosa; A. P. Zuker

    1998-09-23T23:59:59.000Z

    Binding energies and other global properties of nuclei in the middle of the $pf$ shell, such as M1, E2 and Gamow-Teller sum rules, have been obtained using a new Shell Model code (NATHAN) written in quasi-spin formalism and using a $j-j$-coupled basis. An extensive comparison is made with the recently available Shell Model Monte Carlo results using the effective interaction KB3. The binding energies for -nearly- all the $1f_{7/2}$ nuclei are compared with the measured (and extrapolated) results.

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

    SciTech Connect (OSTI)

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

    2014-09-04T23:59:59.000Z

    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).

  3. Atmospheric Oxygen Binding and Hole Doping in Deformed Graphene on a SiO2 Substrate

    E-Print Network [OSTI]

    Sunmin Ryu; Li Liu; Stephane Berciaud; Young-Jun Yu; Haitao Liu; Philip Kim; George W. Flynn; Louis E. Brus

    2010-11-13T23:59:59.000Z

    Using micro-Raman spectroscopy and scanning tunneling microscopy, we study the relationship between structural distortion and electrical hole doping of graphene on a silicon dioxide substrate. The observed upshift of the Raman G band represents charge doping and not compressive strain. Two independent factors control the doping: (1) the degree of graphene coupling to the substrate, and (2) exposure to oxygen and moisture. Thermal annealing induces a pronounced structural distortion due to close coupling to SiO2 and activates the ability of diatomic oxygen to accept charge from graphene. Gas flow experiments show that dry oxygen reversibly dopes graphene; doping becomes stronger and more irreversible in the presence of moisture and over long periods of time. We propose that oxygen molecular anions are stabilized by water solvation and electrostatic binding to the silicon dioxide surface.

  4. Neuronal differentiation modulates the dystrophin Dp71d binding to the nuclear matrix

    SciTech Connect (OSTI)

    Rodriguez-Munoz, Rafael; Villarreal-Silva, Marcela; Gonzalez-Ramirez, Ricardo [Departamento de Genetica y Biologia Molecular, Centro de Investigacion y de Estudios Avanzados del IPN, Avenida Instituto Politecnico Nacional 2508, Apartado Postal 14-740, C.P. 07360, Mexico D.F. (Mexico); Garcia-Sierra, Francisco [Departamento de Biologia Celular, Centro de Investigacion y de Estudios Avanzados del IPN, Avenida Instituto Politecnico Nacional 2508, Apartado Postal 14-740, C.P. 07360, Mexico D.F. (Mexico); Mondragon, Monica; Mondragon, Ricardo [Departamento de Bioquimica, Centro de Investigacion y de Estudios Avanzados del IPN, Avenida Instituto Politecnico Nacional 2508, Apartado Postal 14-740, C.P. 07360, Mexico D.F. (Mexico); Cerna, Joel [Facultad de Medicina, Universidad de Colima, Avenida Universidad 333. C.P. 28040 Colima, Col. (Mexico); Cisneros, Bulmaro [Departamento de Genetica y Biologia Molecular, Centro de Investigacion y de Estudios Avanzados del IPN, Avenida Instituto Politecnico Nacional 2508, Apartado Postal 14-740, C.P. 07360, Mexico D.F. (Mexico)], E-mail: bcisnero@cinvestav.mx

    2008-10-24T23:59:59.000Z

    The function of dystrophin Dp71 in neuronal cells remains unknown. To approach this issue, we have selected the PC12 neuronal cell line. These cells express both a Dp71f cytoplasmic variant and a Dp71d nuclear isoform. In this study, we demonstrated by electron and confocal microscopy analyses of in situ nuclear matrices and Western blotting evaluation of cell extracts that Dp71d associates with the nuclear matrix. Interestingly, this binding is modulated during NGF-induced neuronal differentiation of PC12 cells with a twofold increment in the differentiated cells, compared to control cells. Also, distribution of Dp71d along the periphery of the nuclear matrix observed in the undifferentiated cells is replaced by intense fluorescent foci localized in Center of the nucleoskeletal structure. In summary, we revealed that Dp71d is a dynamic component of nuclear matrix that might participate in the nuclear modeling occurring during neuronal differentiation.

  5. Binding energy of singlet excitons and charge transfer complexes in MDMO-PPV:PCBM solar cells

    E-Print Network [OSTI]

    Kern, Julia; Deibel, Carsten; Dyakonov, Vladimir

    2011-01-01T23:59:59.000Z

    The influence of an external electric field on the photoluminescence intensity of singlet excitons and charge transfer complexes is investigated for a poly[2-methoxy-5-(3',7'-dimethyloctyloxy)-1,4-phenylenevinylene] (MDMO-PPV) diode and a bulk heterojunction of the PPV in combination with [6,6]-phenyl-C61 butyric acid methylester (PCBM), respectively. The experimental data is related to the dissociation probability derived from the Onsager-Braun model. In this way, a lower limit for the singlet exciton binding energy of MDMO-PPV is determined as (327 +- 30) meV, whereas a significantly lower value of (203 +- 18) meV is extracted for the charge transfer complex in a MDMO-PPV:PCBM blend.

  6. Morphine-6-glucuronide: analgesic effects and receptor binding profile in rats

    SciTech Connect (OSTI)

    Abbott, F.V.; Palmour, R.M.

    1988-01-01T23:59:59.000Z

    The antinociceptive effects of morphine-6-glucuronide (M6G) were examined in two animal models of pain, the tail immersion test (reflex withdrawal to noxious heat) and the formalin test (behavioral response to minor tissue injury). In the tail immersion test, M6G produced and increase in withdrawal latency that rose rapidly between 0.01 and 0.025 ug ICV or 1 and 2 mg/kg SC. A further increase occurred at doses greater than 0.2 ug ICV or 4 mg/kg SC and was associated with marked catelepsy and cyanosis. Naloxone, 0.1 mg/kg SC, shifted the lower component of the dose-effect relation by a factor of 24. In the formalin test, 0.01 ug M6G ICV produced hyperalgesia, while between 0.05 and 0.2 ug ICV, antinociception increased rapidly without toxicity. The dose effect relations for hyperalgesia and antinociception were shifted to the right by factors of 20- and 3-fold, respectively. By comparison, ICV morphine was 60 (formalin test) to 145-200 (tail immersion test) times less potent than M6G. At sub-nanomolar concentrations, M6G enhanced the binding of (/sup 3/H)-etorphine, (/sup 3/H)-dihydromorphine and (/sup 3/H)-naloxone to rat brain membrane receptors by 20-40%. At higher concentrations, M6G displaced each ligand from binding sites, with K/sub i/ values of about 30 nM, as compared to morphine K/sub i/ values of about 3 nM.

  7. Phospholamban mutants compete with wild type for SERCA binding in living cells

    SciTech Connect (OSTI)

    Gruber, Simon J.; Haydon, Suzanne [Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota Medical School, Minneapolis, MN 55455 (United States)] [Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota Medical School, Minneapolis, MN 55455 (United States); Thomas, David D., E-mail: ddt@umn.edu [Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota Medical School, Minneapolis, MN 55455 (United States)

    2012-04-06T23:59:59.000Z

    Highlights: Black-Right-Pointing-Pointer PLB phosphorylation in HEK cells increased FRET between YFP-PLB and CFP-SERCA. Black-Right-Pointing-Pointer Competition: Expressing loss-of-function PLB mutants in the system decreased FRET. Black-Right-Pointing-Pointer The FRET assay could screen potential therapeutic PLB mutants to activate SERCA. -- Abstract: We have used fluorescent fusion proteins stably expressed in HEK cells to detect directly the interaction between the sarcoplasmic reticulum Ca-ATPase (SERCA) and phospholamban (PLB) in living cells, in order to design PLB mutants for gene therapy. Ca{sup 2+} cycling in muscle cells depends strongly on SERCA. Heart failure (HF), which contributes to 12% of US deaths, typically exhibits decreased SERCA activity, and several potential therapies for HF aim to increase SERCA activity. We are investigating the use of LOF-PLB mutants (PLB{sub M}) as gene therapy vectors to increase SERCA activity. Active SERCA1a and WT-PLB, tagged at their N termini with fluorescent proteins (CFP and YFP), were coexpressed in stable HEK cell lines, and fluorescence resonance energy transfer (FRET) was used to detect their interaction directly. Phosphorylation of PLB, induced by forskolin, caused an increase in FRET from CFP-SERCA to YFP-PLB, indicating that SERCA inhibition can be relieved without dissociation of the complex. This suggests that a LOF mutant might bind to SERCA with sufficient affinity to complete effectively with WT-PLB, thus relieving SERCA inhibition. Therefore, we transiently expressed a series of PLB{sub M} in the CFP-SERCA/YFP-PLB cell line, and found decreased FRET, implying competition between PLB{sub M} and WT-PLB for binding to SERCA. These results establish this FRET assay as a rapid and quantitative means of screening PLB{sub M} for optimization of gene therapy to activate SERCA, as needed for gene therapy in HF.

  8. Structural and Biochemical Determinants of Ligand Binding by the c-di-GMP Riboswitch

    SciTech Connect (OSTI)

    Smith, K.; Lipchock, S; Livingston,; Shanahan, C; Strobel, S

    2010-01-01T23:59:59.000Z

    The bacterial second messenger c-di-GMP is used in many species to control essential processes that allow the organism to adapt to its environment. The c-di-GMP riboswitch (GEMM) is an important downstream target in this signaling pathway and alters gene expression in response to changing concentrations of c-di-GMP. The riboswitch selectively recognizes its second messenger ligand primarily through contacts with two critical nucleotides. However, these two nucleotides are not the most highly conserved residues within the riboswitch sequence. Instead, nucleotides that stack with c-di-GMP and that form tertiary RNA contacts are the most invariant. Biochemical and structural evidence reveals that the most common natural variants are able to make alternative pairing interactions with both guanine bases of the ligand. Additionally, a high-resolution (2.3 {angstrom}) crystal structure of the native complex reveals that a single metal coordinates the c-di-GMP backbone. Evidence is also provided that after transcription of the first nucleotide on the 3{prime}-side of the P1 helix, which is predicted to be the molecular switch, the aptamer is functional for ligand binding. Although large energetic effects occur when several residues in the RNA are altered, mutations at the most conserved positions, rather than at positions that base pair with c-di-GMP, have the most detrimental effects on binding. Many mutants retain sufficient c-di-GMP affinity for the RNA to remain biologically relevant, which suggests that this motif is quite resilient to mutation.

  9. DNA as a target for anticancer compounds: methods to determine the mode of binding and the mechanism of action

    E-Print Network [OSTI]

    Hergenrother, Paul J.

    . A battery of in vitro assays readily distinguishes between DNA intercalation, DNA groove binding-targeting drugs for cancer and beyond, the further discovery and characterization of such compounds are of considerable interest. This review outlines diagnostic experiments useful in characterizing noncovalent drug

  10. 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.; (UTSMC)

    2010-09-21T23:59:59.000Z

    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.

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

    E-Print Network [OSTI]

    Crofts, Antony R.

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

  12. LEUKOTRIENE BLT2 RECEPTOR MONOMERS ACTIVATE THE Gi2 GTP-BINDING PROTEIN MORE EFFICIENTLY THAN DIMERS

    E-Print Network [OSTI]

    Paris-Sud XI, Universit de

    of Pharmaceutical Technology, Jadavpur University, Kolkata 700032, India 5 present address: INSERM U563, Hpital was then successfully refolded to its native state, as measured by high-affinity LTB4 binding in the presence orientation as assessed by fluorescence resonance energy transfer, was then separated from the monomer. Using

  13. Stability of polycrystalline and wurtzite Si nanowires via symmetry-adapted tight-binding objective molecular dynamics

    E-Print Network [OSTI]

    Dumitrica,Traian

    Stability of polycrystalline and wurtzite Si nanowires via symmetry-adapted tight-binding objective polycrystalline of fivefold symmetry and the wurtzite wires of threefold symmetry are the most favorable quasi only low-energy 001 Si sur- faces. In another recent study,10 wurtzite NWs with hexago- nal cross

  14. Specific in vivo binding to the norepinephrine transporter demonstrated with the PET radioligand, (S,S)-[11

    E-Print Network [OSTI]

    Shen, Jun

    to striatum. Pretreatment with the NET ligand, desipramine, decreased the specific binding of (S,S)-[11 C of [11 C]desipramine has been reported [27] but preliminary in vivo data obtained with PET indicated data has not been reported up to date. (S,S)-MeNER (1, Fig. 1) is an O-methyl analog of rebox- etine (2

  15. Direct Binding of pRb/E2F-2 to GATA-1 Regulates Maturation and Terminal Cell Division during

    E-Print Network [OSTI]

    Paris-Sud XI, Universit de

    a tricomplex with the retinoblastoma protein (pRb) and E2F-2. This interaction requires a LXCXE motif mutant unable to bind pRb fails to inhibit cell proliferation and results in mouse embryonic lethality by anemia. These findings clarify the previously suspected cell-autonomous role of pRb during erythropoiesis

  16. The Non-catalytic Chitin-binding Protein CBP21 from Serratia marcescens Is Essential for Chitin Degradation*

    E-Print Network [OSTI]

    van Aalten, Daan

    Degradation* Received for publication, April 25, 2005, and in revised form, May 26, 2005 Published, JBC Papers,4)-linked units of N-acetylglu- cosamine. We show that efficient chitin degradation additionally depends degradation by chitinase B. CBP21 variants with single mutations on the largely polar binding surface lost

  17. Studies on the binding of 5-N-methylated quindoline derivative to human telomeric G-quadruplex

    SciTech Connect (OSTI)

    Xu, Wei; Tan, Jia-Heng; Chen, Shuo-Bin; Hou, Jin-Qiang; Li, Ding [School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006 (China)] [School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006 (China); Huang, Zhi-Shu, E-mail: ceshzs@mail.sysu.edu.cn [School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006 (China)] [School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006 (China); Gu, Lian-Quan, E-mail: cesglq@mail.sysu.edu.cn [School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006 (China)] [School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006 (China)

    2011-03-18T23:59:59.000Z

    Research highlights: {yields} Hydrophobic interaction provided an important driving force for the interaction between ligand and G-quadruplex. {yields} Constrained water molecules were released from surface of G-tetrad upon the formation of the complex. {yields} The end-stacking mode for quindoline derivative was validated through UV-vis, ITC, steady-state, and time-resolved fluorescence experiment. {yields} The binding of compound 1 to quadruplex was found to be a temperature-dependent and enthalpy-entropy compensation process. -- Abstract: Quindoline derivatives as telomeric quadruplex ligands have shown good biological activity for telomerase inhibition. In the present study, we used spectroscopic and calorimetric methods to investigate the interactions between a quindoline derivative (5-methyl-11-(2-morpholinoethylamino)-10-H-indolo-[3,2-b]quinolin-5-ium iodide, compound 1) and human telomeric G-quadruplex. The thermodynamic studies using isothermal titration calorimetry (ITC) indicated that their binding process was temperature-dependent and enthalpy-entropy co-driven. The significant negative heat capacity was obtained experimentally from the temperature dependence of enthalpy changes, which was consistent with that from theoretical calculation, and all suggesting significant hydrophobic contribution to the molecular recognition process. Based on the results from UV-vis, ITC, steady-state and time-resolved fluorescence, their binding mode was determined as two ligand molecules stacking on the quartets on both ends of the quadruplex. These results shed light on rational design and development of quindoline derivatives as G-quadruplex binding ligands.

  18. Nucleoprotein of influenza B virus binds to its type A counterpart and disrupts influenza A viral polymerase complex formation

    SciTech Connect (OSTI)

    Jaru-ampornpan, Peera, E-mail: peera.jar@biotec.or.th; Narkpuk, Jaraspim; Wanitchang, Asawin; Jongkaewwattana, Anan, E-mail: anan.jon@biotec.or.th

    2014-01-03T23:59:59.000Z

    Highlights: FluB nucleoprotein (BNP) can bind to FluA nucleoprotein (ANP). BNPANP interaction inhibits FluA polymerase activity. BNP binding prevents ANP from forming a functional FluA polymerase complex. Nuclear localization of BNP is necessary for FluA polymerase inhibition. Viral RNA is not required for the BNPANP interaction. -- Abstract: Upon co-infection with influenza B virus (FluB), influenza A virus (FluA) replication is substantially impaired. Previously, we have shown that the nucleoprotein of FluB (BNP) can inhibit FluA polymerase machinery, retarding the growth of FluA. However, the molecular mechanism underlying this inhibitory action awaited further investigation. Here, we provide evidence that BNP hinders the proper formation of FluA polymerase complex by competitively binding to the nucleoprotein of FluA. To exert this inhibitory effect, BNP must be localized in the nucleus. The interaction does not require the presence of the viral RNA but needs an intact BNP RNA-binding motif. The results highlight the novel role of BNP as an anti-influenza A viral agent and provide insights into the mechanism of intertypic interference.

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

    E-Print Network [OSTI]

    Wider, Gerhard

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

  20. Metal binding to dissolved organic matter and adsorption to ferrihydrite in shallow peat groundwaters: Application to diamond exploration

    E-Print Network [OSTI]

    Metal binding to dissolved organic matter and adsorption to ferrihydrite in shallow peat t The speciation and solubility of kimberlite pathfinder metals (Ni, Nd, Ba and K) in shallow peat ground- waters with kimberlite pathfinder metals and determine the spatial distribution of those metals in shallow peat

  1. Interactions between ultraviolet light and interleukin-1 on MSH binding in both mouse melanoma and human squamous carcinoma cells

    SciTech Connect (OSTI)

    Birchall, N.; Orlow, S.J.; Kupper, T.; Pawelek, J. (Univ. of Auckland, (New Zealand))

    1991-03-29T23:59:59.000Z

    Interactions between beta-melanotropin (MSH), interleukin 1-a (IL-1), and ultraviolet light (UV) were examined in Cloudman S91 mouse melanoma and RHEK human squamous carcinoma cell lines. The following points were established: (1) both cell lines produced IL-1 and their production was stimulated by exposure of the cells to UV; (2) both cell lines possessed high affinity binding sites for MSH, and their ability to bind MSH was modulated by IL-1; (3) IL-1 exhibited both stimulatory and inhibitory effects on MSH binding to Cloudman cells; and (4) the stimulatory effect of IL-1 on MSH binding to melanoma cells was reflected in enhanced cellular responsiveness to MSH regarding tyrosinase activity (E.C. 1.14.18.1) and melanin content. The findings raise the possibility that interactions between keratinocytes and melanocytes may be regulated by IL-1 and MSH, and suggest a possible mechanism for stimulation of cutaneous melanogenesis by solar radiation: enhancement of MSH receptor activity by induction of IL-1.

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

    E-Print Network [OSTI]

    Jayaram, Bhyravabotla

    Free Energy Component Analysis for Drug Design: A Case Study of HIV-1 Protease-Inhibitor Binding energy component analysis that conveys information on the physicochemical forces driving the protein for a specific protein target if not in the general case. It is here that the free energy component analysis

  3. Mutagenesis of Residue Arg-246 in the Phosphate-binding Subdomain of Catalytic Sites of Escherichia coli F1-ATPase*

    E-Print Network [OSTI]

    Zulfiqar Ahmad

    coli F1-ATPase* Received for publication, April 26, 2004, and in revised form, May 17, 2004 Published Residues responsible for phosphate binding in F1F0- ATP synthase catalytic sites are of significant to impair oxida- tive phosphorylation and to reduce ATPase activity of purified F1 by 100-fold. In contrast

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

    E-Print Network [OSTI]

    Ikura, Mitsuhiko

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

  5. New Method for Calculating the Absolute Free Energy of Binding: The Effect of a Mobile Loop on the Avidin/Biotin Complex

    E-Print Network [OSTI]

    Meirovitch, Hagai

    New Method for Calculating the Absolute Free Energy of Binding: The Effect of a Mobile Loop energy and entropy. HSMD is extended here for the first time for calculating the absolute free energy change to the total free energy of binding is calculated here for the first time. Our result, A0 ) -24

  6. Biochem. J. (2005) 390, 729735 (Printed in Great Britain) doi:10.1042/BJ20050378 729 Phosphorylation of PEA-15 switches its binding specificity from ERK/MAPK

    E-Print Network [OSTI]

    Ramos, Joe W.

    2005-01-01T23:59:59.000Z

    Phosphorylation of PEA-15 switches its binding specificity from ERK/MAPK to FADD Hemamalini RENGANATHAN*, Hema the ERK (extracellular-signal-regulated kinase)/MAPK (mitogen- activated protein kinase) pathway and the death receptor-initiated apoptosis pathway. This is the result of PEA-15 binding to the ERK

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

    E-Print Network [OSTI]

    Lohman, Timothy M.

    E. coli SSB tetramer binds the rst and second molecules of (dT)35 with heat capacities of opposite complex of Escherichia coli SSB tetramer with (dT)70 displays a temperature-dependent sign reversal) to probe whether this effect requires binding of one or two (dX)35 molecules per SSB tetramer. We nd

  8. Stopped-Flow Studies of the Kinetics of Single-Stranded DNA Binding and Wrapping around the Escherichia coli SSB Tetramer

    E-Print Network [OSTI]

    Lohman, Timothy M.

    the Escherichia coli SSB Tetramer Alexander G. Kozlov and Timothy M. Lohman* Department of Biochemistry in which either one molecule of (dT)70 or two molecules of (dT)35 bind per tetramer. Stopped-flow studies. Our results indicate that initial ssDNA binding to the tetramer is very rapid, with a bimolecular rate

  9. Recombinant fusion protein of albumin-retinol binding protein inactivates stellate cells

    SciTech Connect (OSTI)

    Choi, Soyoung; Park, Sangeun; Kim, Suhyun [Laboratory of Cellular Oncology, Korea University Graduate School of Medicine, Ansan, Gyeonggi do 425-707 (Korea, Republic of)] [Laboratory of Cellular Oncology, Korea University Graduate School of Medicine, Ansan, Gyeonggi do 425-707 (Korea, Republic of); Lim, Chaeseung [Department of Laboratory Medicine, Korea University Guro Hospital, Seoul 152-703 (Korea, Republic of)] [Department of Laboratory Medicine, Korea University Guro Hospital, Seoul 152-703 (Korea, Republic of); Kim, Jungho [Department of Life Science, Sogang University, Seoul 121-742 (Korea, Republic of)] [Department of Life Science, Sogang University, Seoul 121-742 (Korea, Republic of); Cha, Dae Ryong [Department of Internal Medicine, Korea University Ansan Hospital, Ansan, Gyeonggi do 425-020 (Korea, Republic of)] [Department of Internal Medicine, Korea University Ansan Hospital, Ansan, Gyeonggi do 425-020 (Korea, Republic of); Oh, Junseo, E-mail: ohjs@korea.ac.kr [Laboratory of Cellular Oncology, Korea University Graduate School of Medicine, Ansan, Gyeonggi do 425-707 (Korea, Republic of)] [Laboratory of Cellular Oncology, Korea University Graduate School of Medicine, Ansan, Gyeonggi do 425-707 (Korea, Republic of)

    2012-02-03T23:59:59.000Z

    Highlights: Black-Right-Pointing-Pointer We designed novel recombinant albumin-RBP fusion proteins. Black-Right-Pointing-Pointer Expression of fusion proteins inactivates pancreatic stellate cells (PSCs). Black-Right-Pointing-Pointer Fusion proteins are successfully internalized into and inactivate PSCs. Black-Right-Pointing-Pointer RBP moiety mediates cell specific uptake of fusion protein. -- Abstract: Quiescent pancreatic- (PSCs) and hepatic- (HSCs) stellate cells store vitamin A (retinol) in lipid droplets via retinol binding protein (RBP) receptor and, when activated by profibrogenic stimuli, they transform into myofibroblast-like cells which play a key role in the fibrogenesis. Despite extensive investigations, there is, however, currently no appropriate therapy available for tissue fibrosis. We previously showed that the expression of albumin, composed of three homologous domains (I-III), inhibits stellate cell activation, which requires its high-affinity fatty acid-binding sites asymmetrically distributed in domain I and III. To attain stellate cell-specific uptake, albumin (domain I/III) was coupled to RBP; RBP-albumin{sup domain} {sup III} (R-III) and albumin{sup domain} {sup I}-RBP-albumin{sup III} (I-R-III). To assess the biological activity of fusion proteins, cultured PSCs were used. Like wild type albumin, expression of R-III or I-R-III in PSCs after passage 2 (activated PSCs) induced phenotypic reversal from activated to fat-storing cells. On the other hand, R-III and I-R-III, but not albumin, secreted from transfected 293 cells were successfully internalized into and inactivated PSCs. FPLC-purified R-III was found to be internalized into PSCs via caveolae-mediated endocytosis, and its efficient cellular uptake was also observed in HSCs and podocytes among several cell lines tested. Moreover, tissue distribution of intravenously injected R-III was closely similar to that of RBP. Therefore, our data suggest that albumin-RBP fusion protein comprises of stellate cell inactivation-inducing moiety and targeting moiety, which may lead to the development of effective anti-fibrotic drug.

  10. Intestinal-fatty acid binding protein and lipid transport in human intestinal epithelial cells

    SciTech Connect (OSTI)

    Montoudis, Alain [Department of Nutrition, Universite de Montreal and Research Center, CHU Sainte Justine, 3175 Cote Ste-Catherine, Montreal, Que., H3T 1C5 (Canada); Delvin, Edgard [Department of Biochemistry, Universite de Montreal and Research Center, CHU Sainte Justine, 3175 Cote Ste-Catherine, Montreal, Que., H3T 1C5 (Canada); Canadian Institute of Health Research, Group of the Functional Development and Physiopathology of the Digestive Tract, and Department of Anatomy and Cellular Biology, Faculty of Medicine and Health Sciences, Universite de Sherbrooke, Sherbrooke, Que., Canada J1H 5N4 (Canada); Menard, Daniel [Department of Pathology and Cell Biology, Universite de Montreal and Research Center, CHU Sainte Justine, 3175 Cote Ste-Catherine, Montreal, Que., H3T 1C5 (Canada); Canadian Institute of Health Research, Group of the Functional Development and Physiopathology of the Digestive Tract, and Department of Anatomy and Cellular Biology, Faculty of Medicine and Health Sciences, Universite de Sherbrooke, Sherbrooke, Que., J1H 5N4 (Canada)] (and others)

    2006-01-06T23:59:59.000Z

    Intestinal-fatty acid binding protein (I-FABP) is a 14-15 kDa cytoplasmic molecule highly expressed in the enterocyte. Although different functions have been proposed for various FABP family members, the specific function of I-FABP in human intestine remains unclear. Here, we studied the role of I-FABP in molecularly modified normal human intestinal epithelial cells (HIEC-6). cDNA transfection resulted in 90-fold I-FABP overexpression compared to cells treated with empty pQCXIP vector. The high-resolution immunogold technique revealed labeling mainly in the cytosol and confirmed the marked phenotype abundance of I-FABP in cDNA transfected cells. I-FABP overexpression was not associated with alterations in cell proliferation and viability. Studies using these transfected cells cultured with [{sup 14}C]oleic acid did not reveal higher efficiency in de novo synthesis or secretion of triglycerides, phospholipids, and cholesteryl esters compared to cells treated with empty pQCXIP vector only. Similarly, the incubation with [{sup 35}S]methionine did not disclose a superiority in the biogenesis of apolipoproteins (apo) A-I, A-IV, B-48, and B-100. Finally, cells transfected with I-FABP did not exhibit an increased production of chylomicrons, VLDL, LDL, and HDL. Our observations establish that I-FABP overexpression in normal HIEC-6 is not related to cell proliferation, lipid esterification, apo synthesis, and lipoprotein assembly, and, therefore, exclude its role in intestinal fat transport.

  11. The Exact Form of the Green's Function of the Hckel (Tight Binding) Model

    E-Print Network [OSTI]

    Ramis Movassagh; Yuta Tsuji; Roald Hoffmann

    2014-08-13T23:59:59.000Z

    The applications of the H\\"uckel (tight binding) model are ubiquitous in quantum chemistry and solid state physics. The matrix representation is isomorphic to an unoriented vertex adjacency matrix of a bipartite graph, which is also the Laplacian matrix plus twice the identity. In this paper, we analytically calculate the determinant and, when it exists, the inverse of this matrix in connection with the Green's function, $\\mathbf{G}$, of the $N\\times N$ H\\"uckel matrix for linear chains and cyclic systems. For an open linear chain we prove that $\\mathbf{G}$ is a real symmetric matrix whose entries are $G\\left(r,s\\right)=\\left(-1\\right)^{\\frac{r+s-1}{2}}$ when $ $$r$ is even and $s

  12. Split green fluorescent protein as a modular binding partner for protein crystallization

    SciTech Connect (OSTI)

    Nguyen, Hau B. [Los Alamos National Laboratory, MS M888, Los Alamos, NM 87545 (United States); Hung, Li-Wei [Los Alamos National Laboratory, MS D454, Los Alamos, NM 87545 (United States); Yeates, Todd O. [University of California, PO Box 951569, Los Angeles, CA 90095 (United States); Terwilliger, Thomas C., E-mail: terwilliger@lanl.gov; Waldo, Geoffrey S., E-mail: terwilliger@lanl.gov [Los Alamos National Laboratory, MS M888, Los Alamos, NM 87545 (United States)

    2013-12-01T23:59:59.000Z

    A strategy using a new split green fluorescent protein (GFP) as a modular binding partner to form stable protein complexes with a target protein is presented. The modular split GFP may open the way to rapidly creating crystallization variants. A modular strategy for protein crystallization using split green fluorescent protein (GFP) as a crystallization partner is demonstrated. Insertion of a hairpin containing GFP ?-strands 10 and 11 into a surface loop of a target protein provides two chain crossings between the target and the reconstituted GFP compared with the single connection afforded by terminal GFP fusions. This strategy was tested by inserting this hairpin into a loop of another fluorescent protein, sfCherry. The crystal structure of the sfCherry-GFP(1011) hairpin in complex with GFP(19) was determined at a resolution of 2.6 . Analysis of the complex shows that the reconstituted GFP is attached to the target protein (sfCherry) in a structurally ordered way. This work opens the way to rapidly creating crystallization variants by reconstituting a target protein bearing the GFP(1011) hairpin with a variety of GFP(19) mutants engineered for favorable crystallization.

  13. Non-specific binding of Na$^+$ and Mg$^{2+}$ to RNA determined by force spectroscopy methods

    E-Print Network [OSTI]

    C. V. Bizarro; A. Alemany; F. Ritort

    2012-06-20T23:59:59.000Z

    RNA duplex stability depends strongly on ionic conditions, and inside cells RNAs are exposed to both monovalent and multivalent ions. Despite recent advances, we do not have general methods to quantitatively account for the effects of monovalent and multivalent ions on RNA stability, and the thermodynamic parameters for secondary structure prediction have only been derived at 1M [Na$^+$]. Here, by mechanically unfolding and folding a 20 bp RNA hairpin using optical tweezers, we study the RNA thermodynamics and kinetics at different monovalent and mixed monovalent/Mg$^{2+}$ salt conditions. We measure the unfolding and folding rupture forces and apply Kramers theory to extract accurate information about the hairpin free energy landscape under tension at a wide range of ionic conditions. We obtain non-specific corrections for the free energy of formation of the RNA hairpin and measure how the distance of the transition state to the folded state changes with force and ionic strength. We experimentally validate the Tightly Bound Ion model and obtain values for the persistence length of ssRNA. Finally, we test the approximate rule by which the non-specific binding affinity of divalent cations at a given concentration is equivalent to that of monovalent cations taken at 100 fold that concentration for small molecular constructs.

  14. Evaluation of selected binding domains for the analysis of ubiquitinated proteomes

    SciTech Connect (OSTI)

    Nakayasu, Ernesto S.; Ansong, Charles; Brown, Joseph N.; Yang, Feng; Lopez-Ferrer, Dani; Qian, Weijun; Smith, Richard D.; Adkins, Joshua N.

    2013-08-07T23:59:59.000Z

    Ubiquitination is an abundant post-translational modification that consists of covalent attachment of a 76 amino acid residue polypeptide, ubiquitin, to lysine residues or the N-terminus of proteins. Mono and polyubiquitination have been shown to be involved in many critical eukaryotic cellular functions. Affinity enrichment of ubiquitinated proteins has enabled the global analysis of this key modification. In this context, the use of ubiquitin-binding domains (UBDs) is a promising, but poorly explored alternative to more broadly used immune-affinity or tagged affinity enrichment methods. Herein we evaluate the application of eight selected UBDs with differing and contrasting affinities for ubiquitination states. We performed a micro-scale proteomic comparison, leading to the identification of ~200 ubiquitinated protein candidates per UBD to facilitate comparisons. Western blot analysis using anti-ubiquitin or monoclonal antibodies against polyubiquitination at lysine 48 and 63 suggests that UBDs from Dsk2 and ubiquilin-1 have the broadest specificity capturing most types of ubiquitination, whereas the one from NBR1 seems to be more selective to polyubiquitination. Our data demonstrate that with optimized purification conditions UBDs can be a useful tool for proteomic applications.

  15. Dissociative Binding of Carboxylic Acid Ligand on Nanoceria Surface in Aqueous Solution: A Joint in Situ Spectroscopic Characterization and First-Principles Study

    SciTech Connect (OSTI)

    Lu, Zhou; Karakoti, Ajay S.; Velarde Ruiz Esparza, Luis A.; Wang, Weina; Yang, Ping; Thevuthasan, Suntharampillai; Wang, Hongfei

    2013-11-21T23:59:59.000Z

    Carboxylic acid is a common ligand anchoring group to functionalize nanoparticle surfaces. Its binding structures and mechanisms as a function of the oxidation states of metal oxide nanoparticle surfaces are not well characterized experimentally. We present an in situ sum frequency generation vibrational spectroscopy (SFG-VS) study on the binding of deuterated acetic acid on ceria nanoparticles in the aqueous solution. In the SFG experiment, ceria nanoparticles were deposited on the flat surface of a CaF2 hemisphere in contact with acetic acid solutions. While the ceria nanoparticle deprotonated the acetic acid, the CaF2 surface could not. Thus, the binding of the deprotonated acetic acid on ceria can be selectively probed. SFG spectra revealed that the binding modes of the carboxylate group depend on the oxidation states of the ceria surfaces. SFG polarization analysis suggested that the bidentate chelating and bridging binding modes co-exist on the reduced ceria surfaces, while the oxidized ceria surfaces are dominated by the bidentate bridging mode. The direct spectroscopic evidence helps to clarify the binding structures and mechanisms on the ceria nanoparticles. Furthermore, the middle-infrared (IR) transparent CaF2 and its chemical inertness make CaF2 and similar substrate materials good candidates for direct SFG-VS measurement of nanoparticle surface reactions and binding chem-istry.

  16. Autoradiographic localization of sigma receptor binding sites in guinea pig and rat central nervous system with (+)3H-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine

    SciTech Connect (OSTI)

    Gundlach, A.L.; Largent, B.L.; Snyder, S.H.

    1986-06-01T23:59:59.000Z

    (+)3H-3-PPP ((+)3H-3-(3-Hydroxyphenyl)-N-(1-propyl)-piperidine) binds with high affinity to brain membranes with a pharmacological profile consistent with that of sigma receptors. The distribution of (+)3H-3-PPP binding sites in brain and spinal cord of both guinea pig and rat has been determined by in vitro autoradiography with binding densities quantitated by computer-assisted densitometry. (+)3H-3-PPP binding to slide-mounted brain sections is saturable and displays high affinity and a pharmacological specificity very similar to sites labeled in homogenates. (+)3H-3-PPP binding sites are heterogeneously distributed. Highest concentrations of binding sites occur in spinal cord, particularly the ventral horn and dorsal root ganglia; the pons-medulla, associated with the cranial nerve and pontine nuclei and throughout the brain stem reticular formation; the cerebellum, over the Purkinje cell layer; the midbrain, particularly the central gray and red nucleus; and hippocampus, over the pyramidal cell layer. Lowest levels are seen in the basal ganglia and parts of the thalamus, while all other areas, including hypothalamus and cerebral cortex, exhibit moderate grain densities. Quinolinic acid-induced lesions of the hippocampus indicate that (+)3H-3-PPP labels hippocampal pyramidal cells and granule cells in the dentate gyrus. Intrastriatal injection of ibotenic acid dramatically reduces (+)3H-3-PPP binding in this area, while injection of 6-hydroxydopamine produces a relatively slight decrease. The distribution of (+)3H-3-PPP binding sites does not correlate with the receptor distribution of any recognized neurotransmitter or neuropeptide, including dopamine. However, there is a notable similarity between the distribution of (+)3H-3-PPP sites and high-affinity binding sites for psychotomimetic opioids, such as the benzomorphan (+)SKF 10,047.

  17. GBR-12909 and fluspirilene potently inhibited binding of ( sup 3 H) (+) 3-PPP to sigma receptors in rat brain

    SciTech Connect (OSTI)

    Contreras, P.C.; Bremer, M.E.; Rao, T.S. (G. D. Searle Co., Chesterfield, MO (USA))

    1990-01-01T23:59:59.000Z

    Fluspirilene and GBR-12909, two compounds structurally similar to BMY-14802 and haloperidol, were assessed for their ability to interact with sigma receptors. Fluspirilene, an antipsychotic agent that interacts potently with dopamine receptors, inhibited the binding of ({sup 3}H)-(+)3-PPP (IC{sub 50} = 380 nM) more potently than rimcazole, a putative sigma antagonist that was tested clinically for antipsychotic activity. GBR-12909, a potent dopamine uptake blocker, also inhibited the binding of ({sup 3}H)-(+)3-PPP with an IC{sub 50} of 48 nM. However, other compounds that block the re-uptake of catecholamines, such as nomifensine, desipramine, imipramine, xylamine, benztropine and cocaine, were much weaker than GBR-12909as sigma ligands. Thus, GBR-12909 and fluspirilene, compounds structurally similar to BMY-14802, are potent sigma ligands.

  18. Crystal Structure of 12-Lipoxygenase Catalytic-Domain-Inhibitor Complex Identifies a Substrate-Binding Channel for Catalysis

    SciTech Connect (OSTI)

    Xu, Shu; Mueser, Timothy C.; Marnett, Lawrence J.; Funk, Jr., Max O. (Toledo); (Vanderbilt)

    2014-10-02T23:59:59.000Z

    Lipoxygenases are critical enzymes in the biosynthesis of families of bioactive lipids including compounds with important roles in the initiation and resolution of inflammation and in associated diseases such as diabetes, cardiovascular disease, and cancer. Crystals diffracting to high resolution (1.9 {angstrom}) were obtained for a complex between the catalytic domain of leukocyte 12-lipoxygenase and the isoform-specific inhibitor, 4-(2-oxapentadeca-4-yne)phenylpropanoic acid (OPP). In the three-dimensional structure of the complex, the inhibitor occupied a new U-shaped channel open at one end to the surface of the protein and extending past the redox-active iron site that is essential for catalysis. In models, the channel accommodated arachidonic acid, defining the binding site for the substrate of the catalyzed reaction. There was a void adjacent to the OPP binding site connecting to the surface of the enzyme and providing a plausible access channel for the other substrate, oxygen.

  19. Spread of highly localized wave-packet in the tight-binding lattice: Entropic and information-theoretical characterization

    SciTech Connect (OSTI)

    Cuevas, F.A. [Departamento de Fisica, Universidad Catolica del Norte, Avenida Angamos 0610, Antofagasta (Chile); Curilef, S., E-mail: scurilef@ucn.cl [Departamento de Fisica, Universidad Catolica del Norte, Avenida Angamos 0610, Antofagasta (Chile); Plastino, A.R., E-mail: arplastino@ugr.es [National University La Plata, CREG-UNLP, C.C. 727, 1900 La Plata (Argentina); Instituto Carlos I, Universidad de Granada, Granada (Spain)

    2011-10-15T23:59:59.000Z

    The spread of a wave-packet (or its deformation) is a very important topic in quantum mechanics. Understanding this phenomenon is relevant in connection with the study of diverse physical systems. In this paper we apply various 'spreading measures' to characterize the evolution of an initially localized wave-packet in a tight-binding lattice, with special emphasis on information-theoretical measures. We investigate the behavior of both the probability distribution associated with the wave packet and the concomitant probability current. Complexity measures based upon Renyi entropies appear to be particularly good descriptors of the details of the delocalization process. - Highlights: > Spread of highly localized wave-packet in the tight-binding lattice. > Entropic and information-theoretical characterization is used to understand the delocalization. > The behavior of both the probability distribution and the concomitant probability current is investigated. > Renyi entropies appear to be good descriptors of the details of the delocalization process.

  20. External and Internal Guest Binding of a Highly Charged Supramolecular Host in Water: Deconvoluting the Very Different Thermodynamics

    SciTech Connect (OSTI)

    Sgarlata, Carmelo; Mugridge, Jeffrey; Pluth, Michael; Tiedemann,, Bryan; Zito, Valeria; Arena, Giuseppe; Raymond, Kenneth N.

    2009-07-22T23:59:59.000Z

    NMR, UV-vis and isothermal titration calorimetry (ITC) measurements probe different aspects of competing host-guest equilibria as simple alkylammonium guest molecules interact with both the exterior (ion-association) and interior (encapsulation) of the [Ga{sub 4}L{sub 6}]{sup 12-} supramolecular assembly in water. Data obtained by each independent technique measure different components of the host-guest equilibria and only when analyzed together does a complete picture of the solution thermodynamics emerge. Striking differences between the internal and external guest binding are found. External binding is enthalpy driven and mainly due to attractive interactions between the guests and the exterior surface of the assembly while encapsulation is entropy driven as a result of desolvation and release of solvent molecules from the host cavity.

  1. Structural and Functional Basis of CXCL12 (stromal cell-derived factor-1 alpha) Binding to Heparin

    SciTech Connect (OSTI)

    Murphy,J.; Cho, Y.; Sachpatzidis, A.; Fan, C.; Hodsdon, M.; Lolis, E.

    2007-01-01T23:59:59.000Z

    CXCL12 (SDF-1a) and CXCR4 are critical for embryonic development and cellular migration in adults. These proteins are involved in HIV-1 infection, cancer metastasis, and WHIM disease. Sequestration and presentation of CXCL12 to CXCR4 by glycosaminoglycans (GAGs) is proposed to be important for receptor activation. Mutagenesis has identified CXCL12 residues that bind to heparin. However, the molecular details of this interaction have not yet been determined. Here we demonstrate that soluble heparin and heparan sulfate negatively affect CXCL12-mediated in vitro chemotaxis. We also show that a cluster of basic residues in the dimer interface is required for chemotaxis and is a target for inhibition by heparin. We present structural evidence for binding of an unsaturated heparin disaccharide to CXCL12 attained through solution NMR spectroscopy and x-ray crystallography. Increasing concentrations of the disaccharide altered the two-dimensional 1H-15N-HSQC spectra of CXCL12, which identified two clusters of residues. One cluster corresponds to {beta}-strands in the dimer interface. The second includes the amino-terminal loop and the a-helix. In the x-ray structure two unsaturated disaccharides are present. One is in the dimer interface with direct contacts between residues His25, Lys27, and Arg41 of CXCL12 and the heparin disaccharide. The second disaccharide contacts Ala20, Arg21, Asn30, and Lys64. This is the first x-ray structure of a CXC class chemokine in complex with glycosaminoglycans. Based on the observation of two heparin binding sites, we propose a mechanism in which GAGs bind around CXCL12 dimers as they sequester and present CXCL12 to CXCR4.

  2. Dual Binding of an Antibody and a Small Molecule Increases the Stability of TERRA G-Quadruplex

    E-Print Network [OSTI]

    Yangyuoru, Philip M.; Di Antonio, Marco; Ghimire, Chiran; Biffi, Giulia; Balasubramanian, Shankar; Mao, Hanbin

    2014-11-24T23:59:59.000Z

    RNA Structures DOI: 10.1002/anie.201408113 Dual Binding of an Antibody and a Small Molecule Increases the Stability of TERRA G-Quadruplex** Philip M. Yangyuoru, Marco Di Antonio, Chiran Ghimire, Giulia Biffi, Shankar Balasubramanian,* and Hanbin Mao... the development of [*] P. M. Yangyuoru,[+] C. Ghimire, Prof. H. Mao Department of Chemistry and Biochemistry Kent State University, Kent, OH 44242 (USA) E-mail: hmao@kent.edu Dr. M. Di Antonio,[+] Prof. S. Balasubramanian Department of Chemistry, University...

  3. TIN2 Binds TRF1 and TRF2 Simultaneously and Stabilizes the TRF2 Complex on Telomeres*

    E-Print Network [OSTI]

    de Lange, Titia

    TIN2 Binds TRF1 and TRF2 Simultaneously and Stabilizes the TRF2 Complex on Telomeres* Received interacting partner, TIN2, as well as PIP1 and POT1 and regulates telomere-length homeo- stasis. The TRF2 that TRF1, TIN2, PIP1, and POT1 are associated with the TRF2-hRap1 complex. Gel filtration identified a TRF

  4. Evidence for separate substrate binding sites for hydrogen peroxide and cumene hydroperoxide (CHP) in the oxidation of ethanol by catalase

    SciTech Connect (OSTI)

    DeMaster, E.G.; Nagasawa,ss H.T.

    1986-03-01T23:59:59.000Z

    The oxidation of ethanol by purified bovine liver catalase (Sigma, C-40) can be supported by H/sub 2/O/sub 2/ or by CHP. The time course of the H/sub 2/O/sub 2/ supported reaction (using glucose/glucose oxidase as the H/sub 2/O/sub 2/ source) was linear for at least one hr, whereas the rate of acetaldehyde formation in the CHP (4.2 mM) supported reaction decreased with time. When catalase was exposed o CHP for 5 min before the addition of ethanol, the rate of CHP supported ethanol oxidation was reduced by more than 90% compared to incubations where the addition of ethanol preceded that of CHP. In the CHP inhibited state, the peroxidative activity of catalase was not restored by further addition of CHP or ethanol; however, addition of fresh catalase yielded its expected activity. Significantly, the CHP inhibited enzyme was equally effective as the untreated enzyme in catalyzing (a) the oxidation of ethanol in the presence H/sub 2/O/sub 2/ supported peroxidative activity as well as catalytic activity by CHP inhibited catalase points to separate binding sites for H/sub 2/O/sub 2/ and CHP in this reaction. Alternatively, CHP may bind adjacent to a common peroxide active site, thereby sterically impeding the binding of CHP - but not of H/sub 2/O/sub 2/ - to this active site.

  5. Identification and characterization of (/sup 3/H)-rauwolscine binding to alpha2-adrenoceptors in the canine saphenous vein

    SciTech Connect (OSTI)

    Gout, B.

    1988-01-01T23:59:59.000Z

    The biochemical exploration of the alpha2-adrenergic receptors was investigated in the canine saphenous vein using the highly selective alpha2-adrenergic antagonist rauwolscine as a tritiated ligand. Following an enzymatic digestive pretreatment, the authors isolated a purified smooth muscle cell membranes fraction from saphenous veins in quantity sufficient to permit them to study the venous alpha2-adrenoreceptor content. The binding of tritiated rauwolscine was rapid, specific, saturable and reversible. The presence of high affinity sites with a density of binding Bmax of 125.2 /+ -/ 43.1 fmol/mg protein was demonstrated on a unique class of non interacting sites. The kinetically derived Kd was 1.28 nM, in good agreement with the value obtained from saturation isotherms. The pharmacological profile of these sites was assessed by the comparison of the potency of alpha-adrenergic agonists and antagonists to inhibit 1 nM (/sup 3/H)-rauwolscine. Their efficacy was respectively: rauwolscine > phentolamine > RX 781094 > clonidine >> prazosin > (-)-phenylephrine > (-)-noradrenaline. The results showed that (/sup 3/H)-rauwolscine bound specifically to sites in their membranal preparation, which had the pharmacological characteristics of the alpha2-adrenoceptors. The correlation between biochemical and pharmacological data revealed the usefulness of binding methods in the further study of adrenergic mechanisms in the canine saphenous vein.

  6. 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 (Michigan)

    2014-10-02T23:59:59.000Z

    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.

  7. Laminopathy-inducing lamin A mutants can induce redistribution of lamin binding proteins into nuclear aggregates

    SciTech Connect (OSTI)

    Huebner, S. [Department of Biochemistry and Molecular Biology, Nuclear Signalling Laboratory, PO Box 13D, Monash University, Clayton, Victoria 3800 (Australia)]. E-mail: stefan.huebner@med.monash.edu.au; Eam, J.E. [Department of Biochemistry and Molecular Biology, Nuclear Signalling Laboratory, PO Box 13D, Monash University, Clayton, Victoria 3800 (Australia); Huebner, A. [Department of Biochemistry and Molecular Biology, Nuclear Signalling Laboratory, PO Box 13D, Monash University, Clayton, Victoria 3800 (Australia); Jans, D.A. [Department of Biochemistry and Molecular Biology, Nuclear Signalling Laboratory, PO Box 13D, Monash University, Clayton, Victoria 3800 (Australia)

    2006-01-15T23:59:59.000Z

    Lamins, members of the family of intermediate filaments, form a supportive nucleoskeletal structure underlying the nuclear envelope and can also form intranuclear structures. Mutations within the A-type lamin gene cause a variety of degenerative diseases which are collectively referred to as laminopathies. At the molecular level, laminopathies have been shown to be linked to a discontinuous localization pattern of A-type lamins, with some laminopathies containing nuclear lamin A aggregates. Since nuclear aggregate formation could lead to the mislocalization of proteins interacting with A-type lamins, we set out to examine the effects of FLAG-lamin A N195K and R386K protein aggregate formation on the subnuclear distribution of the retinoblastoma protein (pRb) and the sterol responsive element binding protein 1a (SREBP1a) after coexpression as GFP-fusion proteins in HeLa cells. We observed strong recruitment of both proteins into nuclear aggregates. Nuclear aggregate recruitment of the NPC component nucleoporin NUP153 was also observed and found to be dependent on the N-terminus. That these effects were specific was implied by the fact that a number of other coexpressed karyophilic GFP-fusion proteins, such as the nucleoporin NUP98 and kanadaptin, did not coaggregate with FLAG-lamin A N195K or R386K. Immunofluorescence analysis further indicated that the precursor form of lamin A, pre-lamin A, could be found in intranuclear aggregates. Our results imply that redistribution into lamin A-/pre-lamin A-containing aggregates of proteins such as pRb and SREBP1a could represent a key aspect underlying the molecular pathogenesis of certain laminopathies.

  8. Substrate Binding Mode and its Implication on Drug Design for Botulinum Neurotoxin A

    SciTech Connect (OSTI)

    Kumaran, D.; Rawat, R; Ahmed, A; Swaminathan, S

    2008-01-01T23:59:59.000Z

    The seven antigenically distinct serotypes of Clostridium botulinum neurotoxins, the causative agents of botulism, block the neurotransmitter release by specifically cleaving one of the three SNARE proteins and induce flaccid paralysis. The Centers for Disease Control and Prevention (CDC) has declared them as Category A biowarfare agents. The most potent among them, botulinum neurotoxin type A (BoNT/A), cleaves its substrate synaptosome-associated protein of 25 kDa (SNAP-25). An efficient drug for botulism can be developed only with the knowledge of interactions between the substrate and enzyme at the active site. Here, we report the crystal structures of the catalytic domain of BoNT/A with its uncleavable SNAP-25 peptide 197QRATKM202 and its variant 197RRATKM202 to 1.5 A and 1.6 A, respectively. This is the first time the structure of an uncleavable substrate bound to an active botulinum neurotoxin is reported and it has helped in unequivocally defining S1 to S5? sites. These substrate peptides make interactions with the enzyme predominantly by the residues from 160, 200, 250 and 370 loops. Most notably, the amino nitrogen and carbonyl oxygen of P1 residue (Gln197) chelate the zinc ion and replace the nucleophilic water. The P1?-Arg198, occupies the S1? site formed by Arg363, Thr220, Asp370, Thr215, Ile161, Phe163 and Phe194. The S2? subsite is formed by Arg363, Asn368 and Asp370, while S3? subsite is formed by Tyr251, Leu256, Val258, Tyr366, Phe369 and Asn388. P4?-Lys201 makes hydrogen bond with Gln162. P5?-Met202 binds in the hydrophobic pocket formed by the residues from the 250 and 200 loop. Knowledge of interactions between the enzyme and substrate peptide from these complex structures should form the basis for design of potent inhibitors for this neurotoxin.

  9. Binding of misonidazole to V79 spheroids and fragments of Dunning rat prostatic and human colon carcinomas in vitro: diffusion of oxygen and reactive metabolites

    SciTech Connect (OSTI)

    Franko, A.J.; Koch, C.J.

    1984-08-01T23:59:59.000Z

    Differences were noted previously in the binding of /sup 14/C-Misonidazole (MISO) to V79 and EMT6 spheroids when incubated at low oxygen levels. Further data reported here indicate that the K/sub m/ for the inhibition of binding by oxygen is lower in V79 than EMT6 spheroids, so that part of the non-uniformity of binding to V79 spheroids can be explained by diffusion of small amounts of oxygen through the entire rim of viable cells. Diffusion of reactive metabolites of MISO out of the spheroid previously was considered an unlikely explanation. Further evidence to support this interpretation is presented here. Patterns of binding of /sup 3/H-MISO to Dunning and human colon carcinomas are presented which are consistent with the interpretation that most of the reactive metabolites are confined to the cell in which they are produced.

  10. This article was processed using the L a T E X macro package with LLNCS style brain manages to circumvent the binding problem altogether with the help of

    E-Print Network [OSTI]

    Triesch, Jochen

    recordings, optical imaging using voltage sensitive dyes, EEG or MEG. We suggest that the spatial resolution to circumvent the binding problem altogether with the help of combination­coding cells, in spite of all

  11. Loss of the retinoblastoma binding protein 2 (RBP2) histone demethylase suppresses tumorigenesis in mice lacking Rb1 or Men1

    E-Print Network [OSTI]

    Lin, Wenchu

    Aberrations in epigenetic processes, such as histone methylation, can cause cancer. Retinoblastoma binding protein 2 (RBP2; also called JARID1A or KDM5A) can demethylate tri- and dimethylated lysine 4 in histone H3, which ...

  12. Protein-only mechanism induces self-perpetuating changes in the activity of neuronal Aplysia cytoplasmic polyadenylation element binding protein (CPEB)

    E-Print Network [OSTI]

    Heinrich, Sven U.

    Neuronal cytoplasmic polyadenylation element binding protein (CPEB) plays a critical role in maintaining the functional and morphological long-lasting synaptic changes that underlie learning and memory. It can undergo a ...

  13. Histidine-Mediated pH-Sensitive Regulation of M-Ficolin:GlcNAc Binding in Innate Immunity Examined by Molecular Dynamics Simulations

    E-Print Network [OSTI]

    Yang, Linfeng

    Background: M-ficolin, a pathogen recognition molecule in the innate immune system, binds sugar residues including N-acetyl-D-glucosamine (GlcNAc), which is displayed on invading microbes and on apoptotic cells. The cis ...

  14. The structure of SecB/OmpA as visualized by electron microscopy: The mature region of the precursor protein binds asymmetrically to SecB

    SciTech Connect (OSTI)

    Tang, Ying; Pan, Xijiang [State-Key Laboratory of Biomembrane and Membrane Biotechnology, Center for Structural Biology, School of Life Science, Tsinghua University, Beijing 100084 (China)] [State-Key Laboratory of Biomembrane and Membrane Biotechnology, Center for Structural Biology, School of Life Science, Tsinghua University, Beijing 100084 (China); Tai, Phang C. [Department of Biology, Georgia State University, Atlanta, GA 30303 (United States)] [Department of Biology, Georgia State University, Atlanta, GA 30303 (United States); Sui, Sen-Fang, E-mail: suisf@mail.tsinghua.edu.cn [State-Key Laboratory of Biomembrane and Membrane Biotechnology, Center for Structural Biology, School of Life Science, Tsinghua University, Beijing 100084 (China)] [State-Key Laboratory of Biomembrane and Membrane Biotechnology, Center for Structural Biology, School of Life Science, Tsinghua University, Beijing 100084 (China)

    2010-03-19T23:59:59.000Z

    SecB, a molecular chaperone in Escherichia coli, binds a subset of precursor proteins that are exported across the plasma membrane via the Sec pathway. Previous studies showed that SecB bound directly to the mature region rather than to the signal sequence of the precursor protein. To determine the binding pattern of SecB and the mature region of the preprotein, here, we visualized the structure of the SecB/OmpA complex by electron microscopy. This complex is composed by two parts: the main density represents one SecB tetramer and the unfolded part of OmpA wrapping round it; the elongated smaller density represents the rest of OmpA. Each SecB protomer makes a different contribution to the binding of SecB with OmpA. The binding pattern between SecB tetramer and OmpA is asymmetric.

  15. 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 [Departament de Qumica, Universitat Autnoma de Barcelona, Bellaterra 08193 (Spain); Rodriguez-Rodrguez, Cristina [Medicinal Inorganic Chemistry Group, Department of Chemistry, University of British Columbia, 2036 Main Mall, Vancouver, BC, V6T 1Z1 (Canada)

    2014-10-06T23:59:59.000Z

    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.

  16. Fermi Site Office CX Determinations | U.S. DOE Office of Science...

    Office of Science (SC) Website

    Fermi Site Office CX Determinations Integrated Support Center (ISC) ISC Home About Services Freedom of Information Act (FOIA) Privacy Act Categorical Exclusion Determinations...

  17. NF-{kappa}B suppresses HIF-1{alpha} response by competing for P300 binding

    SciTech Connect (OSTI)

    Mendonca, Daniela B.S., E-mail: daniela_mendonca@dentistry.unc.edu [Universidade Catolica de Brasilia, Pos-Graduacao em Ciencias Genomicas e Biotecnologia, SGAN Quadra 916, Av. W5 Norte, 70790-160 Brasilia, DF (Brazil); Bone Biology and Implant Therapy Laboratory, Department of Prosthodontics, University of North Carolina at Chapel Hill, 330 Brauer Hall, CB 7450, Chapel Hill, NC 27599 (United States); Mendonca, Gustavo [Universidade Catolica de Brasilia, Pos-Graduacao em Ciencias Genomicas e Biotecnologia, SGAN Quadra 916, Av. W5 Norte, 70790-160 Brasilia, DF (Brazil) [Universidade Catolica de Brasilia, Pos-Graduacao em Ciencias Genomicas e Biotecnologia, SGAN Quadra 916, Av. W5 Norte, 70790-160 Brasilia, DF (Brazil); Bone Biology and Implant Therapy Laboratory, Department of Prosthodontics, University of North Carolina at Chapel Hill, 330 Brauer Hall, CB 7450, Chapel Hill, NC 27599 (United States); Aragao, Francisco J.L. [Universidade Catolica de Brasilia, Pos-Graduacao em Ciencias Genomicas e Biotecnologia, SGAN Quadra 916, Av. W5 Norte, 70790-160 Brasilia, DF (Brazil) [Universidade Catolica de Brasilia, Pos-Graduacao em Ciencias Genomicas e Biotecnologia, SGAN Quadra 916, Av. W5 Norte, 70790-160 Brasilia, DF (Brazil); Embrapa Recursos Geneticos e Biotecnologia, Laboratorio de Introducao e Expressao de Genes, PqEB W5 Norte, 70770-900 Brasilia, DF (Brazil); Cooper, Lyndon F., E-mail: lyndon_cooper@dentistry.unc.edu [Bone Biology and Implant Therapy Laboratory, Department of Prosthodontics, University of North Carolina at Chapel Hill, 330 Brauer Hall, CB 7450, Chapel Hill, NC 27599 (United States)

    2011-01-28T23:59:59.000Z

    Research highlights: {yields} p65 completely blocked HIF-1{alpha} activity at the HRE on different cell lines. {yields} p65 caused minor changes in HIF-1{alpha} and HIF-1{alpha} target genes mRNA expression. {yields} p65 reduced transcription of VEGF promoter. {yields} p65 competes with HIF-1{alpha} for p300. -- Abstract: Hypoxia has emerged as a key determinant of osteogenesis. HIF-1{alpha} is the transcription factor mediating hypoxia responses that include induction of VEGF and related bone induction. Inflammatory signals antagonize bone repair via the NF-{kappa}B pathway. The present investigation explored the functional relationship of hypoxia (HIF-1{alpha} function) and inflammatory signaling (NF-{kappa}B) in stem like and osteoprogenitor cell lines. The potential interaction between HIF-1{alpha} and NF-{kappa}B signaling was explored by co-transfection studies in hFOB with p65, HIF-1{alpha} and 9x-HRE-luc or HIF-1{alpha} target genes reporter plasmids. Nuclear cross-talk was directly tested using the mammalian Gal4/VP16 two-hybrid, and confirmed by co-immunoprecipitation/western blotting assays. The results show that inflammatory stimulation (TNF-{alpha} treatment) causes a marked inhibition of HIF-1{alpha} function at the HRE in all cell lines studied. Also, co-transfection with p65 expression vector leads to reduced hVEGFp transcription after DFO-induced hypoxia. However, TNF-{alpha} treatment had little effect on HIF-1{alpha} mRNA levels. The functional interaction of Gal4-HIF-1{alpha} and VP16-p300 fusion proteins is effectively blocked by expression of p65 in a dose dependent manner. It was concluded that NF-{kappa}B-mediated inflammatory signaling is able to block HIF-1{alpha} transactivation at HRE-encoding genes by direct competition for p300 binding at the promoter. Inflammation may influence the stem cell niche and tissue regeneration by influencing cellular responses to hypoxia.

  18. 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

    2014-01-03T23:59:59.000Z

    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.

  19. Near-infrared fluorescence glucose sensing based on glucose/galactose-binding protein coupled to 651-Blue Oxazine

    SciTech Connect (OSTI)

    Khan, Faaizah; Pickup, John C., E-mail: john.pickup@kcl.ac.uk

    2013-08-30T23:59:59.000Z

    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.

  20. Structure and interactions of the C-terminal metal binding domain of Archaeoglobus fulgidus CopA

    SciTech Connect (OSTI)

    Agarwal, S.; Hong, D.; Desai, N.K.; H.Sazinsky, M.; Argello, J.M.; Rosenzweig, A.C. (NWU)

    2010-08-13T23:59:59.000Z

    The Cu(+)-ATPase CopA from Archaeoglobus fulgidus belongs to the P(1B) family of the P-type ATPases. These integral membrane proteins couple the energy of ATP hydrolysis to heavy metal ion translocation across membranes. A defining feature of P(1B-1)-type ATPases is the presence of soluble metal binding domains at the N-terminus (N-MBDs). The N-MBDs exhibit a conserved ferredoxin-like fold, similar to that of soluble copper chaperones, and bind metal ions via a conserved CXXC motif. The N-MBDs enable Cu(+) regulation of turnover rates apparently through Cu-sensitive interactions with catalytic domains. A. fulgidus CopA is unusual in that it contains both an N-terminal MBD and a C-terminal MBD (C-MBD). The functional role of the unique C-MBD has not been established. Here, we report the crystal structure of the apo, oxidized C-MBD to 2.0 A resolution. In the structure, two C-MBD monomers form a domain-swapped dimer, which has not been observed previously for similar domains. In addition, the interaction of the C-MBD with the other cytoplasmic domains of CopA, the ATP binding domain (ATPBD) and actuator domain (A-domain), has been investigated. Interestingly, the C-MBD interacts specifically with both of these domains, independent of the presence of Cu(+) or nucleotides. These data reinforce the uniqueness of the C-MBD and suggest a distinct structural role for the C-MBD in CopA transport.