allosteric regulation

Summary

Top Publications

  1. ncbi An allosteric mechanism for activation of the kinase domain of epidermal growth factor receptor
    Xuewu Zhang
    Department of Molecular and Cell Biology, Howard Hughes Medical Institute, University of California, Berkeley, 94720, USA
    Cell 125:1137-49. 2006
  2. ncbi Allostery and the Monod-Wyman-Changeux model after 50 years
    Jean Pierre Changeux
    Collège de France and Institut Pasteur, URA CNRS 2182, Paris Cedex 15 75724, France
    Annu Rev Biophys 41:103-33. 2012
  3. pmc Structural basis for allosteric regulation of GPCRs by sodium ions
    Wei Liu
    Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
    Science 337:232-6. 2012
  4. ncbi Ribonucleotide reductases
    Pär Nordlund
    Division of Biophysics and 2Division of Biochemistry, Medical Nobel Institute, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S 17177 Stockholm, Sweden
    Annu Rev Biochem 75:681-706. 2006
  5. ncbi Targeting cancer with small molecule kinase inhibitors
    Jianming Zhang
    Dana Farber Cancer Institute, Department of Cancer Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nat Rev Cancer 9:28-39. 2009
  6. ncbi The structural basis of function in Cys-loop receptors
    Andrew J Thompson
    Department of Biochemistry, University of Cambridge, Building O, Downing Site, Cambridge CB2 1QW, UK
    Q Rev Biophys 43:449-99. 2010
  7. ncbi Allosteric regulation and catalysis emerge via a common route
    Nina M Goodey
    Montclair State University, Department of Chemistry and Biochemistry, 1 Normal Avenue, Montclair, New Jersey 07043, USA
    Nat Chem Biol 4:474-82. 2008
  8. ncbi Mechanism of activation of the RAF-ERK signaling pathway by oncogenic mutations of B-RAF
    Paul T C Wan
    Section of Structural Biology, The Institute of Cancer Research, Chester Beatty Laboratories, 237 Fulham Road, London SW3 6JB, UK
    Cell 116:855-67. 2004
  9. ncbi Mechanism of CDK activation revealed by the structure of a cyclinA-CDK2 complex
    P D Jeffrey
    Cellular Biochemistry and Biophysics Program, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
    Nature 376:313-20. 1995
  10. pmc Detection of allosteric signal transmission by information-theoretic analysis of protein dynamics
    Alessandro Pandini
    Division of Mathematical Biology, Medical Research Council National Institute for Medical Research, London, UK
    FASEB J 26:868-81. 2012

Detail Information

Publications338 found, 100 shown here

  1. ncbi An allosteric mechanism for activation of the kinase domain of epidermal growth factor receptor
    Xuewu Zhang
    Department of Molecular and Cell Biology, Howard Hughes Medical Institute, University of California, Berkeley, 94720, USA
    Cell 125:1137-49. 2006
    ..The CDK/cyclin-like complex formed by two kinase domains thus explains the activation of EGFR-family receptors by homo- or heterodimerization...
  2. ncbi Allostery and the Monod-Wyman-Changeux model after 50 years
    Jean Pierre Changeux
    Collège de France and Institut Pasteur, URA CNRS 2182, Paris Cedex 15 75724, France
    Annu Rev Biophys 41:103-33. 2012
    ..New questions are raised concerning the dynamics of the allosteric transitions and more complex supramolecular ensembles...
  3. pmc Structural basis for allosteric regulation of GPCRs by sodium ions
    Wei Liu
    Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
    Science 337:232-6. 2012
    ..These high-resolution details shed light on the potential role of structured water molecules, sodium ions, and lipids/cholesterol in GPCR stabilization and function...
  4. ncbi Ribonucleotide reductases
    Pär Nordlund
    Division of Biophysics and 2Division of Biochemistry, Medical Nobel Institute, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S 17177 Stockholm, Sweden
    Annu Rev Biochem 75:681-706. 2006
    ..studies of members from each class have led to a deeper understanding of their catalytic mechanism and allosteric regulation by nucleoside triphosphates...
  5. ncbi Targeting cancer with small molecule kinase inhibitors
    Jianming Zhang
    Dana Farber Cancer Institute, Department of Cancer Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nat Rev Cancer 9:28-39. 2009
    ..This Review provides a broad overview of some of the approaches currently used to discover and characterize new kinase inhibitors...
  6. ncbi The structural basis of function in Cys-loop receptors
    Andrew J Thompson
    Department of Biochemistry, University of Cambridge, Building O, Downing Site, Cambridge CB2 1QW, UK
    Q Rev Biophys 43:449-99. 2010
    ..We also describe some of the current methods that are beginning to reveal the differences between different receptor states, and may ultimately show structural details of transitions between them...
  7. ncbi Allosteric regulation and catalysis emerge via a common route
    Nina M Goodey
    Montclair State University, Department of Chemistry and Biochemistry, 1 Normal Avenue, Montclair, New Jersey 07043, USA
    Nat Chem Biol 4:474-82. 2008
    b>Allosteric regulation of protein function is a mechanism by which an event in one place of a protein structure causes an effect at another site, much like the behavior of a telecommunications network in which a collection of transmitters,..
  8. ncbi Mechanism of activation of the RAF-ERK signaling pathway by oncogenic mutations of B-RAF
    Paul T C Wan
    Section of Structural Biology, The Institute of Cancer Research, Chester Beatty Laboratories, 237 Fulham Road, London SW3 6JB, UK
    Cell 116:855-67. 2004
    ..The high activity mutants signal to ERK by directly phosphorylating MEK, whereas the impaired activity mutants stimulate MEK by activating endogenous C-RAF, possibly via an allosteric or transphosphorylation mechanism...
  9. ncbi Mechanism of CDK activation revealed by the structure of a cyclinA-CDK2 complex
    P D Jeffrey
    Cellular Biochemistry and Biophysics Program, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
    Nature 376:313-20. 1995
    ..These changes activate the kinase by realigning active site residues and relieving the steric blockade at the entrance of the catalytic cleft...
  10. pmc Detection of allosteric signal transmission by information-theoretic analysis of protein dynamics
    Alessandro Pandini
    Division of Mathematical Biology, Medical Research Council National Institute for Medical Research, London, UK
    FASEB J 26:868-81. 2012
    ..In particular, we showed that a preorganized network of fragment connections between the allosteric and functional sites exists already in the inactive state of all three proteins...
  11. pmc The origin of allosteric functional modulation: multiple pre-existing pathways
    Antonio del Sol
    Bioinformatics Research Unit, Research and Development Division, Fujirebio Inc, Hachioji shi, Tokyo, Japan
    Structure 17:1042-50. 2009
    ....
  12. pmc ASD: a comprehensive database of allosteric proteins and modulators
    Zhimin Huang
    The Department of Pathophysiology, Chemical Biology Division, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Universities E Institutes, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
    Nucleic Acids Res 39:D663-9. 2011
    ..Therefore, ASD could be a platform and a starting point for biologists and medicinal chemists for furthering allosteric research. ASD is freely available at http://mdl.shsmu.edu.cn/ASD/...
  13. ncbi Multiple regulatory sites in large-conductance calcium-activated potassium channels
    Xiao Ming Xia
    Department of Anesthesiology, Washington University School of Medicine, Box 8054, St Louis, Missouri 63110, USA
    Nature 418:880-4. 2002
    ..This allows BK channels to serve a variety of physiological roles contingent on the Ca(2+) concentration to which the channels are exposed...
  14. ncbi Aptamers for allosteric regulation
    Jan L Vinkenborg
    Life and Medical Sciences Institute, Chemical Biology and Medicinal Chemistry Unit, Laboratory of Chemical Biology, Rheinische Friedrich Wilhelms Universitat Bonn, Bonn, Germany
    Nat Chem Biol 7:519-27. 2011
    Aptamers are useful for allosteric regulation because they are nucleic acid-based structures in which ligand binding induces conformational changes that may alter the function of a connected oligonucleotide at a distant site...
  15. pmc Protein allostery, signal transmission and dynamics: a classification scheme of allosteric mechanisms
    Chung Jung Tsai
    Basic Research Program, SAIC Frederick, Inc, Center for Cancer Research Nanobiology Program, NCI Frederick, Frederick, MD 21702, USA
    Mol Biosyst 5:207-16. 2009
    ..We further provide a range of examples illustrating mechanisms in protein allostery and their classification from the cellular functional standpoint...
  16. ncbi Allostery wiring diagrams in the transitions that drive the GroEL reaction cycle
    RIINA TEHVER
    Biophysics Program, Institute for Physical Science and Technology, University of Maryland, College Park, MD 20742, USA
    J Mol Biol 387:390-406. 2009
    ..We find that several substrate protein binding residues as well as sites related to ATPase activity belong to a single functional network in GroEL. For GroES, the mobile loop residues and GroES/GroES interface residues are linked...
  17. pmc Allosteric transitions in biological nanomachines are described by robust normal modes of elastic networks
    Wenjun Zheng
    Physics Department, University at Buffalo, Buffalo, NY 14260, USA
    Curr Protein Pept Sci 10:128-32. 2009
    ....
  18. pmc Allosteric modulators of GPCRs: a novel approach for the treatment of CNS disorders
    P Jeffrey Conn
    Department of Pharmacology, Vanderbilt Program in Drug Discovery, Vanderbilt Medical Center, 1215 Light Hall, Nashville, Tennessee 37232, USA
    Nat Rev Drug Discov 8:41-54. 2009
    ..These compounds provide high selectivity, novel modes of efficacy and may lead to novel therapeutic agents for the treatment of multiple psychiatric and neurological human disorders...
  19. ncbi The origin of protein interactions and allostery in colocalization
    John Kuriyan
    Howard Hughes Medical Institute, California Institute for Quantitative Biosciences, Department of Molecular and Cell Biology, University of California, Berkeley, California 94720, USA
    Nature 450:983-90. 2007
    ..Thus, the regulated protein networks of organisms seem to be the inevitable consequence of natural selection operating under physical laws...
  20. pmc Allosteric signal transmission in the nucleotide-binding domain of 70-kDa heat shock protein (Hsp70) molecular chaperones
    Anastasia Zhuravleva
    Department of Biochemistry and Molecular Biology, University of Massachusetts, Amherst, MA 01003, USA
    Proc Natl Acad Sci U S A 108:6987-92. 2011
    ..Thus, a pathway of allosteric communication leads from the NBD nucleotide-binding site to the substrate-binding domain via the interdomain linker...
  21. ncbi Structural basis for allosteric regulation of the monomeric allosteric enzyme human glucokinase
    Kenji Kamata
    Banyu Tsukuba Research Institute in collaboration with Merck Research Laboratories, Okubo 3, Tsukuba, Ibaraki 300 2611, Japan
    Structure 12:429-38. 2004
    ..This finding provided the mechanistic basis for activation of glucokinase as a potential therapeutic approach for treating type 2 diabetes mellitus...
  22. ncbi Dissecting the role of 5'-AMP for allosteric stimulation, activation, and deactivation of AMP-activated protein kinase
    Marianne Suter
    Institute of Cell Biology, Schafmattstrasse 18, ETH Zurich, 8093 Zurich, Switzerland
    J Biol Chem 281:32207-16. 2006
    ..These data shed new light on physiologically important aspects of AMPK regulation...
  23. pmc Hot spots for allosteric regulation on protein surfaces
    Kimberly A Reynolds
    Green Center for Systems Biology and Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX 75390 9050, USA
    Cell 147:1564-75. 2011
    ..These findings suggest that sectors enable the evolution of intermolecular communication and regulation...
  24. pmc Allosteric communication in myosin V: from small conformational changes to large directed movements
    M Cecchini
    Laboratoire de Chimie Biophysique, Universite Louis Pasteur, ISIS, Strasbourg, France
    PLoS Comput Biol 4:e1000129. 2008
    ..The mechanism of the uncoupling of the converter from the motor head, an essential part of the transition, is elucidated. The origin of the partial untwisting of the central beta-sheet in the rigor to post-rigor transition is described...
  25. pmc Allosteric regulation of histidine kinases by their cognate response regulator determines cell fate
    Ralf Paul
    Biozentrum, University of Basel, Klingelbergstrasse 70, 4056 Basel, Switzerland
    Cell 133:452-61. 2008
    ..crescentus. Thus, single domain response regulators can facilitate crosstalk, feedback control, and long-range communication among members of the two-component network...
  26. ncbi Allosteric mechanisms of signal transduction
    Jean Pierre Changeux
    Receptors and Cognition, Institut Pasteur, 75724 Paris Cedex 15, France
    Science 308:1424-8. 2005
    ..We review the MWC theory and its applications for the understanding of signal transduction in biology, and also identify remaining issues that deserve theoretical and experimental substantiation...
  27. pmc Surface sites for engineering allosteric control in proteins
    Jeeyeon Lee
    Department of Chemistry, Pennsylvania State University, University Park, PA 16802, USA
    Science 322:438-42. 2008
    ..PAS-DHFR serves as a proof of concept for engineering regulatory activities into proteins through interface design at conserved allosteric sites...
  28. ncbi Structural basis for tumor pyruvate kinase M2 allosteric regulation and catalysis
    Jill D Dombrauckas
    Center for Pharmaceutical Biotechnology and Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, Chicago, Illinois 60607, USA
    Biochemistry 44:9417-29. 2005
    ....
  29. ncbi Allosteric modulation of G protein-coupled receptors
    Lauren T May
    Department of Pharmacology, University of Melbourne, 3010 Parkville, Victoria
    Annu Rev Pharmacol Toxicol 47:1-51. 2007
    ..Studies are also beginning to unravel the structural basis of allosteric modulation of GPCRs. It remains to be determined whether such modulation represents interactions within monomers versus across dimers...
  30. ncbi The Ste5 scaffold allosterically modulates signaling output of the yeast mating pathway
    Roby P Bhattacharyya
    Department of Cellular and Molecular Pharmacology, University of California San Francisco, 600 16th Street, San Francisco, CA 94143 2240, USA
    Science 311:822-6. 2006
    ..Thus, scaffolds not only direct basic pathway connectivity but can precisely tune quantitative pathway input-output properties...
  31. ncbi Allosteric effects of Pit-1 DNA sites on long-term repression in cell type specification
    K M Scully
    Howard Hughes Medical Institute, Department of Endocrinology and Metabolism, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA
    Science 290:1127-31. 2000
    ....
  32. ncbi Tight steric closure at the intracellular activation gate of a voltage-gated K(+) channel
    D del Camino
    Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA
    Neuron 32:649-56. 2001
    ..Either these Kv channels have a broader inner entrance than seen in the KcsA crystal, even in the closed state, or the region is highly flexible (but nevertheless remains very securely closed nearby)...
  33. pmc Allosteric modulation of DNA by small molecules
    David M Chenoweth
    Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA
    Proc Natl Acad Sci U S A 106:13175-9. 2009
    ..This allosteric perturbation of the DNA helix provides a molecular basis for disruption of transcription factor-DNA interfaces by small molecules, a minimum step in chemical control of gene networks...
  34. pmc Markov propagation of allosteric effects in biomolecular systems: application to GroEL-GroES
    Chakra Chennubhotla
    Department of Computational Biology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA
    Mol Syst Biol 2:36. 2006
    ..Comparison with collective modes deduced from normal mode analysis reveals the propensity of global hinge regions to act as messengers in the transmission of allosteric signals...
  35. pmc Intrinsic dynamics of enzymes in the unbound state and relation to allosteric regulation
    Ivet Bahar
    Department of Computational Biology, School of Medicine, University of Pittsburgh, Suite 3064, Biomedical Science Tower 3, 3051 Fifth Avenue, Pittsburgh, PA 15213, USA
    Curr Opin Struct Biol 17:633-40. 2007
    ..This ability is structure-encoded, and plays a key role in facilitating allosteric regulation, which suggests complementing the sequence-encodes-structure paradigm of protein science by structure-..
  36. ncbi Protein dynamics and allostery: an NMR view
    Shiou Ru Tzeng
    Department of Chemistry and Chemical Biology, Rutgers University, Piscataway, NJ 08854, USA
    Curr Opin Struct Biol 21:62-7. 2011
    ..In several cases allosteric interactions proceed with minimal or no structural changes. We discuss emerging paradigms for the central role of protein dynamics in allostery...
  37. ncbi Asymmetric tyrosine kinase arrangements in activation or autophosphorylation of receptor tyrosine kinases
    Jae Hyun Bae
    Department of Pharmacology, Yale University School of Medicine, 333 Cedar St, New Haven, CT 06520 8066, USA
    Mol Cells 29:443-8. 2010
    ..These studies demonstrate that asymmetric dimer formation is as a common phenomenon critical for activation and autophosphorylation of RTKs...
  38. ncbi Allosteric regulation of estrogen receptor structure, function, and coactivator recruitment by different estrogen response elements
    Julie M Hall
    Receptor Biology Section, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA
    Mol Endocrinol 16:469-86. 2002
    ....
  39. pmc Rational engineering of enzyme allosteric regulation through sequence evolution analysis
    Jae Seong Yang
    School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology, Pohang, Gyeongbuk, Korea
    PLoS Comput Biol 8:e1002612. 2012
    Control of enzyme allosteric regulation is required to drive metabolic flux toward desired levels...
  40. pmc Allosteric modulators of NR2B-containing NMDA receptors: molecular mechanisms and therapeutic potential
    Laetitia Mony
    Laboratoire de Neurobiologie, Ecole Normale Superieure, CNRS, Paris, France
    Br J Pharmacol 157:1301-17. 2009
    ..A better understanding of how NR2B-containing NMDARs (and NMDARs in general) operate and how they can be modulated should help define new strategies to counteract the deleterious effects of dysregulated NMDAR activity...
  41. pmc Structural changes involved in protein binding correlate with intrinsic motions of proteins in the unbound state
    Dror Tobi
    Department of Computational Biology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15261, USA
    Proc Natl Acad Sci U S A 102:18908-13. 2005
    ....
  42. pmc Agonism/antagonism switching in allosteric ensembles
    Hesam N Motlagh
    T C Jenkins Department of Biophysics, Department of Biology, Johns Hopkins University, Baltimore, MD 21212, USA
    Proc Natl Acad Sci U S A 109:4134-9. 2012
    ....
  43. pmc Allosteric regulation of SERCA by phosphorylation-mediated conformational shift of phospholamban
    Martin Gustavsson
    Department of Biochemistry, Molecular Biology, and Biophysics and Department of Chemistry, University of Minnesota, Minneapolis, MN 55455
    Proc Natl Acad Sci U S A 110:17338-43. 2013
    ..We found that the allosteric regulation of SERCA depends on the conformational equilibrium of PLN, whose cytoplasmic regulatory domain ..
  44. pmc Understanding biomolecular motion, recognition, and allostery by use of conformational ensembles
    R Bryn Fenwick
    Joint BSC IRB Research Programme in Computational Biology, Institute for Research in Biomedicine, IRB Barcelona, Spain
    Eur Biophys J 40:1339-55. 2011
    ..Finally, we discuss the limitations of conformational ensembles and highlight some potential applications for the future...
  45. ncbi New concepts in drug discovery: collateral efficacy and permissive antagonism
    Terry Kenakin
    GlaxoSmithKline Research and Development, 5 Moore Drive, Research Triangle Park, North Carolina 27709, USA
    Nat Rev Drug Discov 4:919-27. 2005
    ..Here, the design of drugs against HIV is used as an example of how these concepts might be taken into consideration for GPCR-targeted drugs in general...
  46. ncbi Allostery and population shift in drug discovery
    Gozde Kar
    Center for Computational Biology and Bioinformatics and College of Engineering, Koc University Rumelifeneri Yolu, 34450 Sariyer Istanbul, Turkey
    Curr Opin Pharmacol 10:715-22. 2010
    ..Here we present an overview of dynamic conformational ensembles focusing on allosteric events in signaling. We propose that combining equilibrium fluctuation concepts with genomic screens could help drug discovery...
  47. pmc Purification and functional reconstitution of monomeric mu-opioid receptors: allosteric modulation of agonist binding by Gi2
    Adam J Kuszak
    Departments of Pharmacology, University of Michigan, Ann Arbor, Michigan 48109, USA
    J Biol Chem 284:26732-41. 2009
    ..of recent reports, we proposed that the monomeric form of MOR can activate G proteins and be subject to allosteric regulation. A mu-opioid receptor fused to yellow fluorescent protein (YMOR) was constructed and expressed in insect ..
  48. pmc Large-scale allosteric conformational transitions of adenylate kinase appear to involve a population-shift mechanism
    Karunesh Arora
    Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
    Proc Natl Acad Sci U S A 104:18496-501. 2007
    ..Our estimated activation energy barrier for the conformational transition is also in reasonable accord with the experimental findings...
  49. pmc On the conservation of the slow conformational dynamics within the amino acid kinase family: NAGK the paradigm
    Enrique Marcos
    Department of Biological Chemistry and Molecular Modelling, IQAC CSIC, Barcelona, Spain
    PLoS Comput Biol 6:e1000738. 2010
    ....
  50. pmc Catalytic control in the EGF receptor and its connection to general kinase regulatory mechanisms
    Natalia Jura
    Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA
    Mol Cell 42:9-22. 2011
    ..This mechanism, which involves the stabilization of the active conformation of an α helix, has features in common with mechanisms operative in several other kinases...
  51. ncbi A closer view of the conformation of the Lac repressor bound to operator
    C E Bell
    The Johnson Foundation and Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, 37th and Hamilton Walk, Philadelphia, Pennsylvania 19102 6059, USA
    Nat Struct Biol 7:209-14. 2000
    ..An extensive network of interactions between the DNA-binding and core domains of the repressor suggests a possible mechanism for the allosteric transition...
  52. ncbi Allosteric Akt (PKB) inhibitors: discovery and SAR of isozyme selective inhibitors
    Craig W Lindsley
    Department of Medicinal Chemistry, Technology Enabled Synthesis Group, Merck Research Laboratories, Merck and Co, PO Box 4, West Point, PA 19486, USA
    Bioorg Med Chem Lett 15:761-4. 2005
    ..An iterative analog library synthesis approach quickly provided a highly selective Akt1/Akt2 inhibitor that induces apoptosis in tumor cells and inhibits Akt phosphorylation in vivo...
  53. pmc Computational modeling of allosteric communication reveals organizing principles of mutation-induced signaling in ABL and EGFR kinases
    Anshuman Dixit
    Department of Pharmaceutical Chemistry, School of Pharmacy, The University of Kansas, Lawrence, Kansas, United States of America
    PLoS Comput Biol 7:e1002179. 2011
    ..number of allosteric inhibitors call for a systematic strategy to delineate and classify mechanisms of allosteric regulation and long-range communication that control kinase activity...
  54. ncbi Allosteric regulation of Hsp70 chaperones by a proline switch
    Markus Vogel
    Zentrum für Molekulare Biologie der Universität Heidelberg ZMBI, Heidelberg, Germany
    Mol Cell 21:359-67. 2006
    ..The conformation of the proline, acting through an invariant arginine as relay, determines and stabilizes the opened and closed conformation of the substrate binding domain and thereby regulates the chaperone activity of Hsp70...
  55. ncbi Allosteric regulation of glycogen synthase controls glycogen synthesis in muscle
    Michale Bouskila
    University of Dundee, Scotland, UK
    Cell Metab 12:456-66. 2010
    ..Our study provides genetic evidence that allosteric activation of GS is the primary mechanism by which insulin promotes muscle glycogen accumulation in vivo...
  56. pmc On the role of frustration in the energy landscapes of allosteric proteins
    Diego U Ferreiro
    Protein Physiology Lab, Department of Biological Chemistry, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires and Consejo Nacional de Investigaciones Científicas y Técnicas de Argentina, Buenos Aires, Argentina C1428EGA
    Proc Natl Acad Sci U S A 108:3499-503. 2011
    ..We also anecdotally examine some specific examples of complex conformational changes and speculate on the role of frustration in the kinetics of allosteric change...
  57. pmc Structural basis for allosteric regulation of human ribonucleotide reductase by nucleotide-induced oligomerization
    James Wesley Fairman
    Department of Biochemistry, University of Tennessee, Knoxville, TN, USA
    Nat Struct Mol Biol 18:316-22. 2011
    ..Site-directed mutagenesis and functional assays confirm that hexamerization is a prerequisite for inhibition by dATP. Our data indicate a mechanism for regulating RR activity by dATP-induced oligomerization...
  58. pmc Potentiation of alpha7 nicotinic acetylcholine receptors via an allosteric transmembrane site
    Gareth T Young
    Department of Neuroscience, Physiology and Pharmacology, University College London, Gower Street, London WC1E 6BT, United Kingdom
    Proc Natl Acad Sci U S A 105:14686-91. 2008
    ..Our findings suggest that this is a conserved modulatory allosteric site within neurotransmitter-gated ion channels...
  59. pmc Agonist activation of alpha7 nicotinic acetylcholine receptors via an allosteric transmembrane site
    Jaskiran K Gill
    Department of Neuroscience, University College London, London WC1E 6BT, United Kingdom
    Proc Natl Acad Sci U S A 108:5867-72. 2011
    ..Taken together, these findings provide evidence that agonist activation of nAChRs can occur via an allosteric transmembrane site...
  60. ncbi Allosteric regulation of the cAMP receptor protein
    J G Harman
    Department of Chemistry and Biochemistry, Texas Tech University, Lubbock, TX 79409, USA
    Biochim Biophys Acta 1547:1-17. 2001
    ..Interactions between CRP and RNA polymerase at CRP-dependent promoters produce active ternary transcription complexes...
  61. ncbi Structural basis for allostery in integrins and binding to fibrinogen-mimetic therapeutics
    Tsan Xiao
    The CBR Institute for Biomedical Research and Department of Pathology, Harvard Medical School, 200 Longwood Avenue, Boston, Massachusetts 02115, USA
    Nature 432:59-67. 2004
    ..Here, we define with crystal structures the atomic basis for allosteric regulation of the conformation and affinity for ligand of the integrin ectodomain, and how fibrinogen-mimetic ..
  62. pmc Predicting allosteric communication in myosin via a pathway of conserved residues
    Susan Tang
    Department of Bioengineering, Stanford University, Stanford, CA 94305, USA
    J Mol Biol 373:1361-73. 2007
    ..We provide a refined, downloadable application and source code (on https://simtk.org) to share this tool with the wider community (https://simtk.org/home/allopathfinder)...
  63. pmc Molecular basis for the role of glucokinase regulatory protein as the allosteric switch for glucokinase
    Jung Min Choi
    Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 305 701, Korea
    Proc Natl Acad Sci U S A 110:10171-6. 2013
    ..Despite the critical roles of GK and GKRP, the molecular basis for the allosteric regulation mechanism of GK by GKRP remains unclear...
  64. pmc Coherent conformational degrees of freedom as a structural basis for allosteric communication
    Simon Mitternacht
    Computational Biology Unit UNI Research, University of Bergen, Bergen, Norway
    PLoS Comput Biol 7:e1002301. 2011
    Conformational changes in allosteric regulation can to a large extent be described as motion along one or a few coherent degrees of freedom...
  65. pmc State-dependent cAMP binding to functioning HCN channels studied by patch-clamp fluorometry
    Shengjun Wu
    Department of Physiology and Biophysics, Virginia Commonwealth University School of Medicine, Richmond, Virginia, USA
    Biophys J 100:1226-32. 2011
    ..Our results provide what we believe to be new insights into the cAMP-dependent gating in HCN channel and the interpretation of protein allostery for general ligand-gated channels and receptors...
  66. ncbi Dynamic allostery: linkers are not merely flexible
    Buyong Ma
    Basic Science Program, SAIC Frederick, Inc, Center for Cancer Research Nanobiology Program, NCI Frederick, Frederick, MD 21702, USA
    Structure 19:907-17. 2011
    ..We further propose that evolution has optimized the linker sequences and lengths for efficiency, which explains why mutations in linkers may affect protein function and review the literature in this light...
  67. pmc Allosteric regulation of DNA cleavage and sequence-specificity through run-on oligomerization
    Dmitry Lyumkis
    National Resource for Automated Molecular Microscopy, Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
    Structure 21:1848-58. 2013
    ..The hybrid approach reveals an unusual mechanism of enzyme activation that explains SgrAI's oligomerization and allosteric behavior...
  68. pmc Homotropic allosteric regulation in monomeric mammalian glucokinase
    Mioara Larion
    Department of Chemistry and Biochemistry, Florida State University, Tallahassee, FL 32306 4390, USA
    Arch Biochem Biophys 519:103-11. 2012
    ..Mammalian glucokinase is subject to homotropic allosteric regulation by glucose-the steady-state velocity of glucose-6-phosphate production is not hyperbolic, but instead ..
  69. ncbi Rigor-like structures from muscle myosins reveal key mechanical elements in the transduction pathways of this allosteric motor
    Yuting Yang
    Rosenstiel Basic Medical Sciences Research Center, Brandeis University, Waltham, MA 02454, USA
    Structure 15:553-64. 2007
    ..The overall arrangements of subdomains in the motor are relatively conserved in each of the known contractile states, and we explore qualitatively the energetics of these states...
  70. pmc Unsuspected pathway of the allosteric transition in hemoglobin
    Stefan Fischer
    Interdisziplinäres Zentrum für Wissenschaftliches Rechnen Computational Biochemistry, Im Neuenheimer Feld 368, University of Heidelberg, D 69120 Heidelberg, Germany
    Proc Natl Acad Sci U S A 108:5608-13. 2011
    ..The results explain the recent photodissociation measurements, which suggest that the quaternary transition has a fast (2 μs) as well as a slow (20 μs) component and provide a testable model for single molecule FRET experiments...
  71. ncbi Evolution of allosteric models for hemoglobin
    William A Eaton
    Laboratory of Chemical Physics, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892 0520, USA
    IUBMB Life 59:586-99. 2007
    ....
  72. pmc A Monod-Wyman-Changeux mechanism can explain G protein-coupled receptor (GPCR) allosteric modulation
    Meritxell Canals
    Drug Discovery Biology, Medicinal Chemistry, and Department of Pharmacology, Monash Institute of Pharmaceutical Sciences, Monash University, 399 Royal Parade, Parkville, Victoria 3052, Australia
    J Biol Chem 287:650-9. 2012
    ..These findings define a chemical biological framework that can be applied to the study and classification of allosteric modulators across different GPCR families...
  73. ncbi Structure-based prediction of protein-protein binding affinity with consideration of allosteric effect
    Feifei Tian
    Key Laboratory of Biorheological Science and Technology Under Ministry of Education, 111 Project Laboratory of Biomechanics and Tissue Repair, and Bioengineering College, Chongqing University, Chongqing 400044, China
    Amino Acids 43:531-43. 2012
    ..We also give an empirical estimation of the prediction limit r(pred)(2) = 0.80 for structure-based method used to determine protein-protein binding affinity...
  74. pmc NMR insights into protein allostery
    Gregory Manley
    Department of Chemistry, Yale University, 225 Prospect Street, P O Box 208107, New Haven, CT 06520 8107, USA
    Arch Biochem Biophys 519:223-31. 2012
    ..Subsequently, we describe several examples of application of NMR to protein allostery and highlight the unique insight provided by this experimental technique...
  75. pmc Exploiting protein flexibility to predict the location of allosteric sites
    Alejandro Panjkovich
    Institute of Biotechnology and Biomedicine, Universitat Autonoma de Barcelona, 08193 Cerdanyola del Valles, Spain
    BMC Bioinformatics 13:273. 2012
    ..In this article, we describe a simple computational approach, based on the effect allosteric ligands exert on protein flexibility upon binding, to predict the existence and position of allosteric sites on a given protein structure...
  76. ncbi Allosteric regulation of PKM2 allows cellular adaptation to different physiological states
    Dan Y Gui
    Koch Institute for Integrative Cancer Research at Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Sci Signal 6:pe7. 2013
    Pyruvate kinase isoform M2 (PKM2) activity is subject to complex allosteric regulation. Recently, serine and SAICAR (succinylaminoimidazolecarboxamide ribose-5'-phosphate) were identified as previously unrecognized ..
  77. pmc Allosteric opening of the polypeptide-binding site when an Hsp70 binds ATP
    Ruifeng Qi
    Department of Physiology and Biophysics, Virginia Commonwealth University, Richmond, Virginia, USA
    Nat Struct Mol Biol 20:900-7. 2013
    ..These conformational changes, together with our biochemical assays, provide a structural explanation for allosteric coupling in Hsp70 activity. ..
  78. ncbi Protective role for type-1 metabotropic glutamate receptors against spike and wave discharges in the WAG/Rij rat model of absence epilepsy
    R T Ngomba
    Neuromed Institute, Neuropharmacology Unit, Parco Technologico, Località Camerelle 86077, Pozzilli, Isernia, Italy
    Neuropharmacology 60:1281-91. 2011
    ..This article is part of a Special Issue entitled 'Trends in neuropharmacology: in memory of Erminio Costa'...
  79. pmc β-Subunit myristoylation is the gatekeeper for initiating metabolic stress sensing by AMP-activated protein kinase (AMPK)
    Jonathan S Oakhill
    Protein Chemistry and Metabolism, Saint Vincent s Institute of Medical Research, University of Melbourne, 41 Victoria Parade, Fitzroy 3065, Australia
    Proc Natl Acad Sci U S A 107:19237-41. 2010
    ..Our results show that AMP regulates AMPK activation at the initial phosphorylation step, and that β-subunit myristoylation is important for transducing the metabolic stress signal...
  80. ncbi Crystal structures of fructose 1,6-bisphosphatase: mechanism of catalysis and allosteric inhibition revealed in product complexes
    J Y Choe
    Department of Biochemistry, Iowa State University, Ames 50011, USA
    Biochemistry 39:8565-74. 2000
    ..Development of negative charge on the 1-oxygen of F6P is stabilized by its coordination to the Mg(2+) at site 1...
  81. ncbi Allosteric regulation of nucleotidyl cyclases: an emerging pharmacological target
    Roland Seifert
    Institute of Pharmacology, Hannover Medical School, Hannover, Germany
    Sci Signal 5:pe37. 2012
    ..Here, we summarize the current status of such research and discuss future directions in this exciting field...
  82. ncbi Stereoselective kinetics of warfarin binding to human serum albumin: effect of an allosteric interaction
    Ilona Fitos
    Department of Molecular Pharmacology, Institute of Chemistry, Chemical Research Center, Hungarian Academy of Sciences, Budapest, Hungary
    Chirality 14:442-8. 2002
    ..In accordance with the low molar intrinsic fluorescence determined for the stable ternary complex, the amplitude of the decline in fluorescence became larger...
  83. ncbi Crystal structure of ATP sulfurylase from Penicillium chrysogenum: insights into the allosteric regulation of sulfate assimilation
    I J MacRae
    Section of Molecular and Cellular Biology and Department of Chemistry, University of California, One Shields Avenue, Davis, California 95616, USA
    Biochemistry 40:6795-804. 2001
    ..On the other hand, a surface "trench" links each catalytic site in one triad with an allosteric site in the other triad. This trench may be a vestigial feature of a bifunctional ("PAPS synthetase") ancestor of fungal ATP sulfurylase...
  84. ncbi Allostery in a monomeric protein: the case of human serum albumin
    Paolo Ascenzi
    Department of Biology, University Roma Tre, Rome, Italy
    Biophys Chem 148:16-22. 2010
    ..Here, both functional and structural aspects of the allosteric modulation of heme and drug (e.g., warfarin and ibuprofen) binding to HSA and of the drug-dependent reactivity of HSA-heme are reviewed...
  85. ncbi A locally closed conformation of a bacterial pentameric proton-gated ion channel
    Marie S Prevost
    Institut Pasteur, Groupe Récepteurs Canaux, Paris, France
    Nat Struct Mol Biol 19:642-9. 2012
    ..Further cross-linking, accessibility and molecular dynamics data suggest that the locally closed form is a functionally relevant conformation that occurs during allosteric gating transitions...
  86. pmc A series of α7 nicotinic acetylcholine receptor allosteric modulators with close chemical similarity but diverse pharmacological properties
    Jaskiran K Gill
    Department of Neuroscience, Physiology and Pharmacology, University College London, London, UK
    Mol Pharmacol 81:710-8. 2012
    ..These findings provide evidence of the pharmacological diversity of compounds interacting with the allosteric transmembrane site on α7 nAChRs...
  87. pmc Frequency and release flux of calcium sparks in rat cardiac myocytes: a relation to RYR gating
    Alexandra Zahradnikova
    Institute of Molecular Physiology and Genetics, Slovak Academy of Sciences, 833 34 Bratislava, Slovak Republic
    J Gen Physiol 136:101-16. 2010
    ..This mechanism clarifies the unexpectedly low calcium release flux during elementary release events and unifies the theory of calcium signaling in resting and contracting cardiac myocytes...
  88. ncbi G protein coupled receptors as allosteric proteins and the role of allosteric modulators
    Terry Kenakin
    GlaxoSmithKline Research and Development, Research Triangle Park, NC 27709, USA
    J Recept Signal Transduct Res 30:313-21. 2010
    ..Two of these behaviors (namely probe dependence for CCR5-based HIV-1 entry inhibitors and functional selectivity for biased agonism) will be highlighted with examples...
  89. ncbi Allosteric regulation of the transcription factor NFAT1 by multiple phosphorylation sites: a mathematical analysis
    Carlos Salazar
    Theoretische Biophysik, Institut fur Biologie, Humboldt Universitat Berlin, Invalidenstrasse 42, D 10115 Berlin, Germany
    J Mol Biol 327:31-45. 2003
    ..The model predicts that nuclear kinases exert a larger control on the activation threshold than cytoplasmic kinases, and that the NFAT activation kinetics can discriminate between input signals of different amplitude...
  90. pmc Spontaneous channel activity of the inositol 1,4,5-trisphosphate (InsP3) receptor (InsP3R). Application of allosteric modeling to calcium and InsP3 regulation of InsP3R single-channel gating
    Don On Daniel Mak
    Department of Physiology, B39 Anatomy Chemistry, University of Pennsylvania, Philadelphia, PA 19104 6085, USA
    J Gen Physiol 122:583-603. 2003
    ..The validity of this model was established by its successful quantitative prediction of channel behavior after it had been exposed to ultra-low bath [Ca2+]...
  91. pmc Cooperative [Ca²+]-dependent regulation of the rate of myosin binding to actin: solution data and the tropomyosin chain model
    Michael Geeves
    Department of Biosciences, University of Kent, Canterbury, Kent, United Kingdom
    Biophys J 100:2679-87. 2011
    ..Implications for theories of thin-filament regulation in muscle are discussed...
  92. pmc Glycoprotein hormone receptors: link between receptor homodimerization and negative cooperativity
    Eneko Urizar
    IRIBHM, Universite Libre de Bruxelles, Campus Erasme, Brussels, Belgium
    EMBO J 24:1954-64. 2005
    ..This study is the first report of homodimerization associated with negative cooperativity in rhodopsin-like GPCRs. As such, it may warrant revisitation of allosterism in the whole GPCR family...
  93. pmc Dynamically committed, uncommitted, and quenched states encoded in protein kinase A revealed by NMR spectroscopy
    Larry R Masterson
    Department of Biochemistry, University of Minnesota, Minneapolis, MN 55455 0431, USA
    Proc Natl Acad Sci U S A 108:6969-74. 2011
    ..These results unveil the role of internal dynamics in both kinase function and regulation...
  94. pmc NMR reveals novel mechanisms of protein activity regulation
    Charalampos G Kalodimos
    Department of Chemistry and Chemical Biology, Rutgers University, Piscataway, New Jersey 08854, USA
    Protein Sci 20:773-82. 2011
    ..A summary of mechanisms underpinning protein activity regulation revealed by the application of NMR spectroscopy in a number of biological systems studied in the lab is provided...
  95. pmc Allostery in the LacI/GalR family: variations on a theme
    Liskin Swint-Kruse
    Department of Biochemistry and Molecular Biology, The University of Kansas Medical Center, Kansas City, 66160, United States
    Curr Opin Microbiol 12:129-37. 2009
    ..In turn, binding to alternative DNA sequences may impact the degree of allosteric response. Thus, this family exhibits a symphony of variations by which transcriptional control is achieved...
  96. ncbi The anaerobic (class III) ribonucleotide reductase from Lactococcus lactis. Catalytic properties and allosteric regulation of the pure enzyme system
    E Torrents
    Department of Biochemistry 1, Medical Nobel Institute, MBB, Karolinska Institutet, S 17177 Stockholm, Sweden
    J Biol Chem 275:2463-71. 2000
    ..The results with the L. lactis class III reductase further support the concept of a common origin for all present day ribonucleotide reductases...
  97. pmc Allostery and cooperativity revisited
    Qiang Cui
    Department of Chemistry and Theoretical Chemistry Institute, University of Wisconsin, Madison, Wisconsin 53706, USA
    Protein Sci 17:1295-307. 2008
    ..The presentation offers not only an up-to-date description of allostery from a theoretical/computational perspective, but also helps to resolve several outstanding issues concerning allostery...
  98. ncbi Entropy-driven cAMP-dependent allosteric control of inhibitory interactions in exchange proteins directly activated by cAMP
    Rahul Das
    Department of Chemistry, Biochemistry, and Biomedical Sciences, McMaster University, Hamilton, Ontario L8S 4M1, Canada
    J Biol Chem 283:19691-703. 2008
    ....
  99. pmc Thermodynamics-based drug design: strategies for inhibiting protein-protein interactions
    Arne SchOn
    Department of Biology, The Johns Hopkins University, Baltimore, Maryland 21218, USA
    Future Med Chem 3:1129-37. 2011
    ..This rigorous model can be easily applied to the analysis of protein-protein inhibition data and used as a tool in the optimization of inhibitor molecules...
  100. pmc OMP peptides modulate the activity of DegS protease by differential binding to active and inactive conformations
    Jungsan Sohn
    Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Mol Cell 33:64-74. 2009
    ....
  101. pmc Ligand-induced conformational changes and conformational dynamics in the solution structure of the lactose repressor protein
    Marc Taraban
    Department of Chemistry, University of Utah, Salt Lake City, UT 84112, USA
    J Mol Biol 376:466-81. 2008
    ..In gene regulation, such a flexible LacI would be beneficial for the interaction of its two DNA-binding domains, positioned at the tips of the V, with the required two of three LacI operators needed for full repression...

Research Grants65

  1. Nitric Oxide Signaling with Heme Proteins
    William R Montfort; Fiscal Year: 2012
    ..Specific Aim 2 is to understand mechanism in the allosteric regulation of sGC. Experiments involving ligand binding, kinetics, femtosecond photolysis and 2D-IR are proposed...
  2. mTORC1-dependent regulation of the CycC/CDK8 complex
    Jeffrey E Pessin; Fiscal Year: 2013
    ..a complex process that is dependent upon the nutrient/hormone state, availability of substrate precursors, allosteric regulation of key enzymati activity steps, and the transcriptional control of lipogenic gene expression through the ..
  3. Allosteric regulation of the sensory protease DegS
    RANDALL VERNON MAULDIN; Fiscal Year: 2011
    ..The research described in this proposal will broaden and deepen our understanding of the allosteric mechanisms used by the DegS sensory protease to facilitate bacterial survival under inhospitable conditions. ..
  4. Regulation and Catalysis of Human Insulin Degrading Enzyme
    Wei Jen Tang; Fiscal Year: 2013
    ..is that the open-closed conformational switch of IDE is the key regulatory step of IDE that is subject to allosteric regulation by dimerization, posttranslational modifications, cellular factors, and chemical modulators...
  5. Polyamine and trypanothione metabolism in Trypanosoma brucei
    Margaret A Phillips; Fiscal Year: 2013
    ..inhibitors of AdoMetDC and they will provide insight into the general question of the molecular basis for allosteric regulation of protein function...
  6. Receptor disulfide allosteric regulation of anthrax toxin action
    Jianjun Sun; Fiscal Year: 2013
    ..This research will enhance our fundamental understanding of anthrax pathogenesis, which will facilitate development of novel therapeutics against anthrax. ..
  7. Allosteric Regulation of SNAREs and the Rab GEF Mon1 by Phosphoinositides
    Rutilio A Fratti; Fiscal Year: 2013
    ..The proposed study will define how the composition of the vacuolar membrane regulates SNARE and Mon1 function and will give us clues about the relationship between lipid modification and human health and disease. ..
  8. Role of hemoglobin b93cys residue in nitric oxide bioactivity
    RAKESH PRAVINCHANDRA PATEL; Fiscal Year: 2013
    ..adhesion to pulmonary endothelial cells and elicit vasodilation in a manner that is independent on allosteric regulation. Both pulmonary inflammation and lung injury are features of sepsis...
  9. Targeting Trypanosoma brucei S-adenosylmethionine decarboxylase in Drug Discovery
    NAHIR VELEZ; Fiscal Year: 2012
    ..amino acid residues involved in the activation in an attempt to gain insights into the mechanism of allosteric regulation. Next I will characterize species differences in the activation of AdoMetDC by prozyme by comparing the T...
  10. MOLECULAR GENETICS OF ISOCITRATE DEHYDROGENASES
    Lee McAlister Henn; Fiscal Year: 2011
    ..Mitochondrial NAD+-specific isocitrate dehydrogenase (IDH) is sensitive to cellular energy levels due to allosteric regulation by adenine nucleotides and NADH...
  11. Human PBGS Quaternary Structure Dynamics, Drugs, and Half-of-the-sites Reactivity
    Eileen K Jaffe; Fiscal Year: 2012
    ..HSR is similar to allosteric regulation in that binding phenomena at one location in the protein profoundly affect the binding/reactivity behavior ..
  12. Low Activity Oligomers of Porphobilinogen Synthase as Antibiotic Targets
    Eileen K Jaffe; Fiscal Year: 2010
    Abstract: Allosteric regulation through the interconversion of functionally distinct non-additive quaternary structure assemblies has recently been described for the essential enzyme porphobilinogen synthase (PBGS)...
  13. Mechanisms of Allosteric Influence on Enzymes Activity
    GREGORY DUNCAN REINHART; Fiscal Year: 2012
    ..The long-term goal of this research program is to understand the molecular basis for allosteric regulation. Currently we are focused on systems in which allosteric ligands achieve their effects by altering the ..
  14. A Mutagenic Study of Yeast Actin Conformational Changes
    Peter A Rubenstein; Fiscal Year: 2010
    ..The dynamic nature of the actin monomer, both free and within the actin filament, is required for allosteric regulation of actin, both internally, and imposed upon it by an array of actin regulatory proteins...
  15. Structural insights into redox homeostasis
    Joseph J Barycki; Fiscal Year: 2010
    ..We will examine the molecular details of allosteric regulation of glutamate cysteine ligase, which catalyzes the committed step of glutathione bisoynthesis...
  16. Allostery in Hepatitis B Virus Capsid Assembly
    SARAH PALMER KATEN; Fiscal Year: 2010
    ..disulfide on the kinetics of assembly in an effort to characterize the effects of this disulfide on the allosteric regulation of the disulfide...
  17. MOLECULAR BASIS OF HUMAN CYTOCHROME P450 3A FUNCTION
    James R Halpert; Fiscal Year: 2013
    ..The knowledge of the mechanistic basis and physiological role of allosteric regulation of CYP3A4 will provide key information necessary for understanding the mechanisms of adverse drug effects ..
  18. CGMP AND PHOTORECEPTOR FUNCTION
    Rick H Cote; Fiscal Year: 2012
    ..how the structural differences between PDE5 and PDE6 can reveal functional differences in drug binding, allosteric regulation and functional protein expression;and (c) the network of PDE6-interacting proteins and the function they ..
  19. Structural interrogation of allosteric AMPK regulation
    Karsten Melcher; Fiscal Year: 2013
    ..directly activate and inhibit the AMPK kinase activity, respectively, but the mechanism of this direct, allosteric regulation is unknown...
  20. The glucocorticoid receptor as signal integrator: studying ALL drug resistance
    Miles A Pufall; Fiscal Year: 2013
    ..studied signal integration using the glucocorticoid receptor (GR), in particular the mechanistic basis of allosteric regulation by DNA sequence...
  21. TRANSPORT OF NEUROTRANSMITTER INTO SYNAPTIC VESICLES
    Robert H Edwards; Fiscal Year: 2011
    ..In addition, the vesicular glutamate transporters (VGLUTs) show allosteric regulation by chloride and may themselves exhibit a chloride conductance, but the relationship between these ..
  22. STUDIES OF THROMBIN ALLOSTERY
    Enrico Di Cera; Fiscal Year: 2013
    ..the strategy for macromolecular substrate recognition at the active site that leaves exosite I free for allosteric regulation. In specific aim 1, we will test by site-directed mutagenesis the pathway of long-range communication ..
  23. High-throughput assay for protein-ligand interaction
    Vincent T Lee; Fiscal Year: 2012
    ..Protein interactions with low molecular weight ligand have great implication in biology for both allosteric regulation and enzymatic activity...
  24. Vibrational Spectroscopic Investigations of Glutamate Receptor
    Vasanthi Jayaraman; Fiscal Year: 2010
    The specific molecular interactions between glutamate and the glutamate receptor are central to the allosteric regulation of function in this membrane bound protein, which is main excitatory neurotransmitter receptor in the mammalian ..
  25. Allosteric Regulation of Myocardial Contraction
    JOHN MARSHALL ROBINSON; Fiscal Year: 2013
    ..The goal of this project is to establish mechanism of cooperative myofilament activation (Aim 1) and to establish the mechanism of altered myofilament sensitivity to Ca2+ (Aim II). ..
  26. TRANSPORT OF NEUROTRANSMITTER INTO SYNAPTIC VESICLES
    Robert H Edwards; Fiscal Year: 2013
    ..In addition, the vesicular glutamate transporters (VGLUTs) show allosteric regulation by chloride and may themselves exhibit a chloride conductance, but the relationship between these ..
  27. Allosteric Regulation of Ion Channel Gating
    Christopher J Lingle; Fiscal Year: 2013
    ....
  28. Structure and mechanism of zinc efflux transporters
    Dax Fu; Fiscal Year: 2013
    ..The conformational changes underlying the allosteric regulation of zinc transport are yet to be explored...
  29. Regulation of Phenylalanine Catabolism
    Paul F Fitzpatrick; Fiscal Year: 2013
    ..The goal of the research proposed here is to understand the structural and dynamic basis for the allosteric regulation. The proposed experiments will combine modern structural approaches (e.g...
  30. ELECTRON TRANSPORT ENZYMES IN CATECHOLAMINE GRANULES
    Patrick Fleming; Fiscal Year: 1990
    ..The fourth objective is to kinetically characterize the allosteric regulation of DBH by ADP. Standard enzyme assay and computer analysis of the complex kinetics will be used...
  31. DEOXYRIBONUCLEOTIDE METABOLISM IN ESCHERICHIA COLI
    James Fuchs; Fiscal Year: 1992
    ..of all ribonucleotide diphosphates and the substrate specificity and overall activity is controlled by allosteric regulation. The regulation of the synthesis of the enzyme is unusual...
  32. The Partnership for Native American Cancer Prevention (1 of 2)
    William H Wiist; Fiscal Year: 2013
    ..Despite extensive study, little is known about the overall shape of sGC, the means by which allosteric regulation takes place, the arrangement of functional domains in the protein or the arrangement of the protein in the ..
  33. The Partnership for Native American Cancer Prevention (2 of 2)
    TESHIA G ARAMBULA SOLOMON; Fiscal Year: 2013
    ..Despite extensive study, little is known about the overall shape of sGC, the means by which allosteric regulation takes place, the arrangement of functional domains in the protein or the arrangement of the protein in the ..
  34. Mutually exclusive protein folding
    Stewart N Loh; Fiscal Year: 2012
    ..be implemented within a single protein or can be combined with MEF in a two- domain fusion to establish allosteric regulation. The aims will generate biosensors for calcium and sugars, protein scaffolds for development of versatile (..
  35. Development of a library of regulated Actibodies
    Wendy E Thomas; Fiscal Year: 2013
    ..This work will help us understand a newly discovered type of allosteric regulation, and determine whether it is useful for making regulated recognition proteins...
  36. Mechanisms of Neurotransmitter Biosynthesis
    Paul F Fitzpatrick; Fiscal Year: 2011
    ..The kinetics of peptide bond exchange will be used to evaluate a literature model for allosteric regulation of phenylalanine hydroxylase, while fluorescence methods will be used to evaluate a structural model for ..
  37. Structural Investigation of Allosteric Regulation in Bacterial Carbonic Anhydrase
    JEFF CRONK; Fiscal Year: 2007
    ..It integrates a textbook example of an extremely fast enzyme with allosteric regulation of enzyme activity...
  38. MEMBRANE BIOPHYSICS AND CONTROL OF THROMBIN GENERATION
    BARRY LENTZ; Fiscal Year: 1999
    DESCRIPTION: This ongoing project proposes to extend studies of the role(s) of PS allosteric regulation of blood coagulation factors Xa and Va...
  39. Protein Design Using Physical Scoring Functions integrated with Site Couplings
    Junmei Wang; Fiscal Year: 2012
    ..among many proteins plays a significant role in many biological processes, such as signal transmission and allosteric regulation, etc...
  40. DOPAMINE MONOOXYGENASE--MOLECULAR MECHANISMS
    JUDITH KLINMAN; Fiscal Year: 1999
    ..pathway for the biogenesis of soluble vs membrane bound enzyme; (e) further characterization of a proposed allosteric regulation of enzyme by ascorbate; and (f) affinity labelling of the fumarate activator site. III...
  41. ALLOSTERIC REGULATION OF SUBSTRATE CHANNELING
    Michael Dunn; Fiscal Year: 2006
    ..Objectives: Elucidate fundamental relationships of chemical catalysis, enzyme conformational dynamics, allosteric regulation, and enzyme structure to the mechanism of metabolite transfer between enzyme pairs (substrate channeling) ..
  42. RIBONUCLEOTIDE REDUCTASE OF THE MALARIA PARASITE
    Debopam Chakrabarti; Fiscal Year: 2000
    ..Compare the activities of the recombinant and native RNR. 4) Study kinetic properties and the allosteric regulation of the PF RNR...
  43. Regulation of cardiac ion channel function via allosteric modulators
    Andrew Marks; Fiscal Year: 2007
    ..6 (calstabin1/2). Four aims are proposed: Aim 1: Allosteric regulation of RyR2 by small molecules that enhance binding of calstabin2 to RyR2...
  44. Altered phosphodiesterase expression in diseased muscle
    TIMOTHY BLOOM; Fiscal Year: 2007
    ..There are eleven known families of mammalian PDE, differentiated by their substrate specificity, kinetics, allosteric regulation and sensitivity to pharmacologic agents...
  45. ORGANIZATION AND REGULATION OF THE ATCASE CISTRONS
    James Wild; Fiscal Year: 1993
    ..in higher organisms (yeast, myxamoeba, plants and hamster) in order to further an understanding of the allosteric regulation of aspartate transcarbamoylase since extensive chemical, mutational and crystallographic data are ..
  46. COCAINE RECEPTORS AND ADDICTION
    MOHYEE ELDEFRAWI; Fiscal Year: 1993
    ..2- To determine the mechanism of allosteric regulation of the cocaine-sensitive [3H]DA transport by ATP, cations and anions...
  47. EVOLUTION OF ALLOSTERIC REGULATION IN PHOSPHORYLASE
    Robert Fletterick; Fiscal Year: 1999
    ..These basic mechanisms have strong eventual implications for developing therapy to help persons with diabetes and other metabolic disorders, such as hepatic glycogen storage diseases. ..
  48. PHENCYCLIDINE PSYCHOPHARMACOLOGY--SCHIZOPHRENIA
    Daniel Javitt; Fiscal Year: 1990
    ..approaches including N-ethyl maleimide inactivation paradigms will determine the nature of any mutual allosteric regulation. Solubilization techniques modeled after those which have succeeded for other receptor classes will be ..
  49. REGULATION OF ADENINE NUCLEOTIDE POOLS
    Vern Schramm; Fiscal Year: 1993
    ..structure and chemical modification will e used to establish the amino acids involved in catalysis and in allosteric regulation. The role of enzyme-bound zinc in AMP deaminase will be investigated by EPR studies in which Zn(II) is ..
  50. Regulation of Virus Capsid Assembly
    GILLIAN AIR; Fiscal Year: 2007
    ..that (i) in vitro assembly can be correlated with assembly in vivo and (ii) assembly is subject to allosteric regulation. Assembly of the common naturally occurring mutants will be correlated with phenotype...
  51. PROTEIN INTERACTIONS REGULATING CELL MOTILITY
    Wendell Lim; Fiscal Year: 2009
    ..Most of these signaling molecules display complex allosteric regulation. For example, the neuronal Wiskott- Aldrich Syndrome Protein (N-WASP) stimulates actin filament nucleation ..
  52. Studying the dynamics of protein allostery with path-based Markov state models
    ALBERT PAN; Fiscal Year: 2009
    ..simulation methodology is proposed to probe the detailed microscopic mechanisms of voltage-dependent allosteric regulation. Most biomolecular conformational changes occur on timescales which are beyond the ability of current ..
  53. ALLOSTERIC REGULATION OF THE ESTROGEN RECEPTOR BY DNA
    FERN MURDOCH; Fiscal Year: 1999
    ..The results of these experiments will define the role of DNA as an allosteric effector of the estrogen receptor. ..
  54. STRUCTURE-FUNCTION RELATIONSHIPS IN PHOSPHORYLASE A
    Robert Fletterick; Fiscal Year: 1993
    ..The control of the key enzymes of many cellular processes is by allosteric regulation which may be coupled of phosphorylation - a covalent post translation switch that changes protein function...
  55. Structural Studies of Archaeal Ribonucleotide Reductases
    Hector Hernandez; Fiscal Year: 2005
    ..objective of this research proposal is to obtain structural insight into the molecular details of the allosteric regulation of ribonucleotide reductases (RNRs)...
  56. Regulation of Map Kinase by Protein Motions
    Natalie G Ahn; Fiscal Year: 2010
    ..allosterically between their respective binding pockets, and explore the functional consequences of allosteric regulation, using isothermal calorimetry, HX-MS, and NMR. Sp...
  57. Structural Investigations of Guanylyl Cyclase Function
    Patricia Pellicena; Fiscal Year: 2004
    ..Using GC-C as a transmembrane cyclase model, we will investigate the allosteric regulation of the enzyme...
  58. EFC assay to measure Allosteric Regulation of Protein Kinases
    KEITH OLSON; Fiscal Year: 2007
    ..In order to harness EFC to measure allosteric regulation, we will insert the EA and ProLabel fragments into a protein kinase and its allosteric regulator protein...
  59. Regulated Complex Assembly in Membrane-Associated Guanylate Kinases
    RHONDA NEWMAN; Fiscal Year: 2009
    ..In a hypothesized model, allosteric regulation of the intramolecular association of protein domains regulates MAGUK function...
  60. REGULATION OF ANTIGEN PROCESSING
    Peter Jensen; Fiscal Year: 2004
    ..further investigate the structural basis for DM function and to test the hypothesis that DM is subject to allosteric regulation. Additional experiments are proposed to analyze the interaction of class II molecules with tetraspanin ..
  61. REGULATION OF ANTIGEN PROCESSING
    Peter Jensen; Fiscal Year: 2009
    ..further investigate the structural basis for DM function and to test the hypothesis that DM is subject to allosteric regulation. Additional experiments are proposed to analyze the interaction of class II molecules with tetraspanin ..
  62. BASIS FOR NA MODULATION OF ALPHA2 RECEPTOR FUNCTION
    LEE LIMBIRD; Fiscal Year: 1999
    ..discovery that a mutation in a highly conserved residue in the receptor, Asp79Asn, resulted in a loss of allosteric regulation of the receptor to sodium and, more significantly, a selective loss in coupling of the receptor to ..
  63. Antibodies Engineered for Allosteric Control of Binding.
    Iain Peters; Fiscal Year: 2001
    ..The proposed research will test efficacy of a molecular design capable of imposing allosteric regulation on any scFv...
  64. Structural Studies on the Cannabinoid Receptor
    STEVEN MANSOOR; Fiscal Year: 2006
    ..By exploring whether this is true for the CB1 receptor, I will determine if nucleotide allosteric regulation of ligand binding works through inducing conformational changes in the receptor...
  65. Hexameric PBGS as a Bioterrorism Defense
    Eileen Jaffe; Fiscal Year: 2006
    ..Success of the proposed studies will establish a much needed new target for species selective antibiotic development that can be applied to bio-defense against NIAID priority pathogens. ..