Research Topics
Genomes and Genes
Species
| allosteric siteSummarySummary: A site on an enzyme which upon binding of a modulator, causes the protein to undergo a conformational change that may alter the catalytic or binding properties of the enzyme. Top Publications
Research Grants
| Scientific Experts
|
Detail Information
Publications
Structural Basis of allosteric regulation and substrate specificity of the non-phosphorylating glyceraldehyde 3-Phosphate dehydrogenase from Thermoproteus tenaxEsben Lorentzen
European Molecular Biology Laboratory, Hamburg Outstation, Notkestr 85, D 22603 Hamburg, Germany
J Mol Biol 341:815-28. 2004..3 A resolution, which allows us to analyse the structural basis for substrate binding, the mechanism of catalysis as well as the stereoselectivity of the enzymatic reaction...
Small molecule activators of SIRT1 as therapeutics for the treatment of type 2 diabetesJill C Milne
Sirtris Pharmaceuticals Inc, 790 Memorial Drive, Cambridge, Massachusetts 02139, USA
Nature 450:712-6. 2007..These compounds bind to the SIRT1 enzyme-peptide substrate complex at an allosteric site amino-terminal to the catalytic domain and lower the Michaelis constant for acetylated substrates...- Allostery and cooperativity revisitedQiang Cui
Department of Chemistry and Theoretical Chemistry Institute, University of Wisconsin, Madison, Wisconsin 53706, USA
Protein Sci 17:1295-307. 2008..quot; 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... - Computation of conformational coupling in allosteric proteinsBrian A Kidd
Department of Bioengineering, University of Washington, Seattle, Washington, United States of America
PLoS Comput Biol 5:e1000484. 2009.... - BMS-345541 is a highly selective inhibitor of I kappa B kinase that binds at an allosteric site of the enzyme and blocks NF-kappa B-dependent transcription in miceJames R Burke
Department of Immunology, Inflammation and Pulmonary Drug Discovery, Bristol Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543, USA
J Biol Chem 278:1450-6. 2003..Thus, the compound is effective against NF-kappa B activation in mice and represents an important tool for investigating the role of IKK in disease models... - Surface sites for engineering allosteric control in proteinsJeeyeon 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... - IIAGlc inhibition of glycerol kinase: a communications network tunes protein motions at the allosteric sitePeng Yu
Department of Biochemistry and Biophysics and Texas Agricultural Experiment Station, Texas A and M University, College Station, Texas 77843 2128, USA
Biochemistry 46:12355-65. 2007..coli glycerol kinase suggest that motions of the allosteric site have an important role in the inhibition. Three E... - Characterization of the functional role of allosteric site residue Asp102 in the regulatory mechanism of human mitochondrial NAD(P)+-dependent malate dehydrogenase (malic enzyme)Hui Chih Hung
Department of Life Sciences, National Chung Hsing University, Taichung 402, Taiwan, Republic of China
Biochem J 392:39-45. 2005..The Asp102 mutants, however, are much less sensitive to regulation by fumarate. Mutation of Asp102 leads to the desensitization of the co-operative effect between fumarate and substrates of the enzyme... - Pharmacology of the beta-carboline FG-7,142, a partial inverse agonist at the benzodiazepine allosteric site of the GABA A receptor: neurochemical, neurophysiological, and behavioral effectsAndrew K Evans
University of Bristol, Henry Wellcome Laboratories of Integrative Neuroscience and Endocrinology, Bristol, UK
CNS Drug Rev 13:475-501. 2007..beta-carbolines, spanning a spectrum from full agonists to full inverse agonists at the benzodiazepine allosteric site for the GABA(A) receptor, can provide valuable insight into the neural mechanisms underlying anxiety-related .. - Quantitative analysis of DNA binding by the Escherichia coli arginine repressorD Szwajkajzer
Chemistry Department, Princeton University, Princeton, NJ 08544 1009, USA
J Mol Biol 312:949-62. 2001..The results indicate that subunit assembly plays no role in activation, although communication among subunits of the ArgR hexamer is required for specific DNA binding. The data suggest that DNA is also an allosteric effector of ArgR... - CBS domains form energy-sensing modules whose binding of adenosine ligands is disrupted by disease mutationsJohn W Scott
Division of Molecular Physiology, Faculty of Life Sciences, Wellcome Trust Biocentre, University of Dundee, Scotland, United Kingdom
J Clin Invest 113:274-84. 2004..This shows that tandem pairs of CBS domains act, in most cases, as sensors of cellular energy status and, as such, represent a newly identified class of binding domain for adenosine derivatives... - Manipulation of ligand binding affinity by exploitation of conformational couplingJ S Marvin
Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA
Nat Struct Biol 8:795-8. 2001..A family of 20 variants was generated with affinities ranging from an approximately 100-fold improvement (7.4 nM) to an approximately two-fold weakening (1.8 mM) relative to the wild type protein (800 nM)... - Cellular activation of leukocyte function-associated antigen-1 and its affinity are regulated at the I domain allosteric siteM L Lupher
ICOS Corporation, 22021 20th Avenue SE, Bothell, WA 98021, USA
J Immunol 167:1431-9. 2001..Binding of the LFA-1 ligand, ICAM-1 to the metal ion-dependent adhesion site is regulated by the I domain allosteric site (IDAS)... - Searching for new allosteric sites in enzymesJeanne A Hardy
Sunesis Pharmaceuticals Inc, 341 Oyster Point Boulevard, South San Francisco, California 94080, USA
Curr Opin Struct Biol 14:706-15. 2004..By exploring recent structurally well-characterized examples, trends begin to emerge for both the modes of binding and mechanisms of inhibition... - MHC class II allosteric site drugs: new immunotherapeutics for malignant, infectious and autoimmune diseasesM Xu
Antigen Express, Inc, One Innovation Drive, Worcester, MA 01605, USA
Scand J Immunol 54:39-44. 2001..of the 'Ii-Key' segment of the Ii protein with the major histocmpatibility complex (MHC) Class II allosteric site, which is adjacent to the antigenic peptide-binding site, creates therapeutic opportunities by regulating the .. - The 70-kDa heat shock protein chaperone nucleotide-binding domain in solution unveiled as a molecular machine that can reorient its functional subdomainsYongbo Zhang
Biophysics Research Division and Departments of Biological Chemistry and Chemistry, University of Michigan, 930 North University Avenue, Ann Arbor, MI 48109, USA
Proc Natl Acad Sci U S A 101:10272-7. 2004..Our data suggest a hypothesis that cochaperone or substrate domain binding perturbs the relative subdomain orientations, thereby functionally and allosterically coupling to the nucleotide state of the NBD... - Modeling the cAMP-induced allosteric transition using the crystal structure of CAP-cAMP at 2.1 A resolutionJ M Passner
Department of Molecular Biophysics and Biochemistry, Mount Sinai Schoolof Medicine, New York, NY 10029, USA
J Mol Biol 304:847-59. 2000..Additionally, cAMP binding may cause a further rearrangement of the DNA-binding and cAMP-binding domains of CAP via a flap consisting of beta-strands 4 and 5 which lies over the cAMP... - A glycine-dependent riboswitch that uses cooperative binding to control gene expressionMaumita Mandal
Department of Molecular, Cellular, and Developmental Biology, Yale University, Post Office Box 208103, New Haven, CT 06520 8103, USA
Science 306:275-9. 2004..Thus, riboswitches perform key regulatory roles and exhibit complex performance characteristics that previously had been observed only with protein factors... - Structural basis for allostery in integrins and binding to fibrinogen-mimetic therapeuticsTsan 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..Allostery in the head thus disrupts interaction between the legs in a previously described low-affinity bent integrin conformation, and leg extension positions the high-affinity head far above the cell surface... - Discovery of an allosteric site in the caspasesJeanne A Hardy
Sunesis Pharmaceuticals, Inc, 341 Oyster Point Boulevard, South San Francisco, CA 94080, USA
Proc Natl Acad Sci U S A 101:12461-6. 2004..We discovered a previously unreported and conserved allosteric site in a deep cavity at the dimer interface 14 A from the active site... - Residue Asp-189 controls both substrate binding and the monovalent cation specificity of thrombinSwati Prasad
Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St Louis, Missouri 63110, USA
J Biol Chem 279:10103-8. 2004.... - G protein-coupled receptor allosterism and complexingArthur Christopoulos
Department of Pharmacology, University of Melbourne, Parkville, Victoria, Australia
Pharmacol Rev 54:323-74. 2002..It is proposed that the study of allosteric phenomena will become of progressively greater import to the drug discovery process due to the advent of newer and more sensitive GPCR screening technologies... - Expression, purification and characterization of human glutamate dehydrogenase (GDH) allosteric regulatory mutationsJie Fang
Division of Endocrinology, The Children s Hospital of Philadelphia, 34th Street and Civic Center Boulevard, Philadelphia, PA 19104, USA
Biochem J 363:81-7. 2002.... - The structure of apo human glutamate dehydrogenase details subunit communication and allosteryThomas J Smith
Donald Danforth Plant Science Center, 975 North Warson Road, St Louis, MO 63132, USA
J Mol Biol 318:765-77. 2002..These results support the previous proposal that purines regulate GDH activity by altering the dynamics of the NAD binding domain. Finally, a possible structural mechanism for negative cooperativity is presented... - A tertiary two-state allosteric model for hemoglobinEric R Henry
Laboratory of Chemical Physics, Building 5, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-0520, USA
Biophys Chem 98:149-64. 2002..The model is consistent with the results of solution, gel, and single crystal oxygen binding studies, but underestimates the population of doubly-liganded molecules determined in low-temperature electrophoresis experiments... - Cooperativity in transcription factor binding to the coactivator CREB-binding protein (CBP). The mixed lineage leukemia protein (MLL) activation domain binds to an allosteric site on the KIX domainNatalie K Goto
Department of Molecular Biology and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, California 92037, USA
J Biol Chem 277:43168-74. 2002..In the case of MLL and c-Myb, both proteins are involved in proliferation of hematopoietic cells and leukemogenesis, and synergistic interactions mediated by CBP may play a functional role... - The modular logic of signaling proteins: building allosteric switches from simple binding domainsWendell A Lim
Department of Cellular and Molecular Pharmacology, Department of Biochemistry and Biophysics, University of California, San Francisco 94143 0450, USA
Curr Opin Struct Biol 12:61-8. 2002..A combination of structural, biophysical and computational studies is beginning to shed light on the fundamental principles governing this type of modular allostery... - Thiamine derivatives bind messenger RNAs directly to regulate bacterial gene expressionWade Winkler
Department of Molecular, Cellular and Developmental Biology, Yale University, PO Box 208103, New Haven, Connecticut 06520 8103, USA
Nature 419:952-6. 2002..This metabolite-sensing regulatory system provides an example of a 'riboswitch' whose evolutionary origin might pre-date the emergence of proteins... - Non-nucleoside analogue inhibitors bind to an allosteric site on HCV NS5B polymerase. Crystal structures and mechanism of inhibitionMeitian Wang
Canadian Institutes for Health Research Group in Protein Structure and Function, Department of Biochemistry, University of Alberta, Edmonton, Alberta T6G 2H7, Canada
J Biol Chem 278:9489-95. 2003..The location of this inhibitor-binding site suggests that the binding of these inhibitors interferes with a conformational change essential for the activity of the polymerase... - Interactions of orthosteric and allosteric ligands with [3H]dimethyl-W84 at the common allosteric site of muscarinic M2 receptorsChristian Tränkle
Department of Pharmacology and Toxicology, Institute of Pharmacy, University of Bonn, Gerhard Domagk Strasse 3, D 53121 Bonn, Germany
Mol Pharmacol 64:180-90. 2003An optimized assay for the binding of [3H]dimethyl-W84 to its allosteric site on M2 muscarinic receptors has been used to directly measure the affinities of allosteric ligands... - "Ping-pong" interactions between mitochondrial tRNA import receptors within a multiprotein complexSubhendra Nath Bhattacharyya
Indian Institute of Chemical Biology, 4 Raja S.C. Mullick Road, Calcutta 700032, India
Mol Cell Biol 23:5217-24. 2003..This "ping-pong" mechanism may be an effective means to maintain a balanced tRNA pool for mitochondrial translation... - Kinetic and allosteric consequences of mutations in the subunit and domain interfaces and the allosteric site of yeast pyruvate kinaseAron W Fenton
Department of Biochemistry and Molecular Biology, Oklahoma State University, Stillwater, Oklahoma 74078, USA
Arch Biochem Biophys 397:28-39. 2002..None of the seven A [bond] C domain interface mutations altered allostery. A model that includes a central role for E392 in allosteric regulation of yeast PK is proposed... - Allosteric determinants in guanine nucleotide-binding proteinsMark E Hatley
Department of Pharmacology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9050, USA
Proc Natl Acad Sci U S A 100:14445-50. 2003..The network of residues identified by the SCA appears to comprise a core allosteric mechanism conferring nucleotide-dependent switching; the specific features of different G protein family members are built on this core... - Human liver glycogen phosphorylase inhibitors bind at a new allosteric siteV L Rath
Department of Exploratory Medicinal Sciences, Global Research and Development, Pfizer Inc, Groton, CT 06340, USA
Chem Biol 7:677-82. 2000..Maintaining control of blood glucose levels is critical in minimizing the debilitating effects of diabetes, making liver glycogen phosphorylase a potential therapeutic target... - A new allosteric site in glycogen phosphorylase b as a target for drug interactionsN G Oikonomakos
Institute of Biological Research and Biotechnology, The National Hellenic Research Foundation, Athens, 11635, Greece eie gr
Structure 8:575-84. 2000..Structural studies have been carried out in order to establish the mechanism of this unusual inhibitor... - An RNA-binding respiratory component mediates import of type II tRNAs into Leishmania mitochondriaSaibal Chatterjee
Genetic Engineering Laboratory, Indian Institute of Chemical Biology, Calcutta 700032, India
J Biol Chem 281:25270-7. 2006.... - Local motions in a benchmark of allosteric proteinsMichael D Daily
Program in Molecular and Computational Biophysics, Johns Hopkins University, Baltimore, Maryland 21218, USA
Proteins 67:385-99. 2007..However, allosteric proteins exhibit twice as much percent motion on average as nonallosteric proteins with ligand-induced motion. These observations may guide efforts to design flexibility and allostery into proteins... - Allosteric small molecules unveil a role of an extracellular E2/transmembrane helix 7 junction for G protein-coupled receptor activationDorothea Jäger
Pharmacology and Toxicology Section, Institute of Pharmacy, Rheinische Friedrich Wilhelms University, D 53121 Bonn, Germany
J Biol Chem 282:34968-76. 2007..we found that the deviating allosteric/orthosteric interactions are mediated through the core region of the allosteric site. A key epitope is M(2)Trp(422) in position 7... - Contact rearrangements form coupled networks from local motions in allosteric proteinsMichael D Daily
Program in Molecular and Computational Biophysics, Johns Hopkins University, Baltimore, Maryland 21218, USA
Proteins 71:455-66. 2008..In summary, residue-residue contact rearrangement networks provide useful representations of the portions of allosteric pathways resulting from coupled local motions... - A kinetic mechanism for nicotinic acetylcholine receptors based on multiple allosteric transitionsS J Edelstein
Departement de Biochimie, Universite de Geneve, Switzerland
Biol Cybern 75:361-79. 1996..In terms of future developments, the analysis presented here provides a physical basis for constructing more biologically realistic models of synaptic modulation that may be applied to artificial neural networks... 
Nicotinic receptors, allosteric proteins and medicineJean Pierre Changeux
Research Unit, National Center of Scientific Research 2182, Department of Neuroscience, Pasteur Institute, Paris, France
Trends Mol Med 14:93-102. 2008....- FimH forms catch bonds that are enhanced by mechanical force due to allosteric regulationOlga Yakovenko
Department of Bioengineering, University of Washington, Seattle, Washington 98195, USA
J Biol Chem 283:11596-605. 2008..Additionally, these observations may provide a means for designing antiadhesive mechanisms... - A monomeric variant of insulin degrading enzyme (IDE) loses its regulatory propertiesEun Suk Song
Department of Molecular and Cellular Biochemistry and the Center for Structural Biology, University of Kentucky, Lexington, Kentucky, United States of America
PLoS ONE 5:e9719. 2010..Insulin degrading enzyme (IDE) is a key enzyme in the metabolism of both insulin and amyloid beta peptides. IDE is unique in that it is subject to allosteric activation which is hypothesized to occur through an oligomeric structure... - Subunit interactions and composition of the fructose 6-phosphate catalytic site and the fructose 2,6-bisphosphate allosteric site of mammalian phosphofructokinaseCristina Ferreras
Departamento de Bioquimica, Facultad de Medicina de la Universidad Autonoma de Madrid, 28029 Madrid, Spain
J Biol Chem 284:9124-31. 2009..prokaryotic gene, with the duplicated fructose 6-phosphate catalytic site in the C-terminal half becoming an allosteric site for the activator fructose 2,6-bisphosphate... - Allosteric site variants of Haemophilus influenzae beta-carbonic anhydraseRoger S Rowlett
Department of Chemistry, Colgate University, 13 Oak Drive, Hamilton, New York 13346, USA
Biochemistry 48:6146-56. 2009..These results lend additional support to the hypothesis that HICA is an allosteric enzyme that can adopt active and inactive conformations, the latter of which is stabilized by bicarbonate ion binding to a non-catalytic site... - Allosteric networks governing regulation and catalysis of Src-family protein tyrosine kinases: implications for disease-associated kinasesHeung Chin Cheng
Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Melbourne, Victoria, Australia
Clin Exp Pharmacol Physiol 37:93-101. 2010..4. Further investigations to decipher the roles of the hydrophobic spine residues in regulation and catalysis of SFKs will benefit the development of therapeutic SFK inhibitors for cancer treatment... - Allosteric disulfide bondsBryan Schmidt
Centre for Vascular Research, University of New South Wales and Department of Haematology, Prince of Wales Hospital, Sydney, New South Wales 2052, Australia
Biochemistry 45:7429-33. 2006..We suggest that the -RHStaple configuration is a hallmark of allosteric disulfides. About 1 in 15 of all structurally determined disulfides is a potential allosteric bond... - Amide hydrogen exchange reveals conformational changes in hsp70 chaperones important for allosteric regulationWolfgang Rist
Zentrum für Molekulare Biologie der Universität Heidelberg ZMBH, Im Neuenheimer Feld 282, 69120 Heidelberg, Germany
J Biol Chem 281:16493-501. 2006..ATP reverts the ATP-induced conformational changes in the linker and selected parts of the NBD. Our data outline a pathway for allosteric interdomain control and suggest an important role of the linker and the base of helix alphaA... - Mutations in the human UDP-N-acetylglucosamine 2-epimerase gene define the disease sialuria and the allosteric site of the enzymeR Seppala
1Section on Human Biochemical Genetics, Heritable Disorders Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892 1830, USA
Am J Hum Genet 64:1563-9. 1999..Their heterozygote mutations, R266W, R266Q, and R263L, indicate that the allosteric site of the epimerase resides in the region of codons 263-266... - Molecular basis and characterization of the hyperinsulinism/hyperammonemia syndrome: predominance of mutations in exons 11 and 12 of the glutamate dehydrogenase gene. HI/HA Contributing InvestigatorsC A Stanley
The Children s Hospital of Philadelphia, Department of Pediatrics, University of Pennsylvania School of Medicine, 19104, USA
Diabetes 49:667-73. 2000..Based on the three-dimensional structure of GDH, the mutations may function by impairing the binding of an inhibitory GTP to a domain responsible for the allosteric and cooperativity properties of GDH... - Thrombin: a paradigm for enzymes allosterically activated by monovalent cationsEnrico Di Cera
Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St Louis, MO 63110, USA
C R Biol 327:1065-76. 2004..formation of a ternary intermediate with the enzyme-substrate complex, or binding of the cation to an allosteric site in the protein. Thrombin is a Na+-activated enzyme with procoagulant, anticoagulant and signaling roles... - Asymmetric and independent contribution of the second transmembrane segment 12' residues to diliganded gating of acetylcholine receptor channels: a single-channel study with choline as the agonistC Grosman
Department of Physiology and Biophysics, State University of New York at Buffalo, Buffalo, New York 14214, USA
J Gen Physiol 115:637-51. 2000.... - Critical amino acid residues of the common allosteric site on the M2 muscarinic acetylcholine receptor: more similarities than differences between the structurally divergent agents gallamine and bis(ammonio)alkane-type hexamethylene-bis-[dimethyl-(3-phthaXi-Ping Huang
Department of Psychiatry, H073, Hershey Medical Center, Penn State College of Medicine, 500 University Drive, Hershey, PA 17033, USA
Mol Pharmacol 68:769-78. 2005..W84) are known to interact competitively at a common allosteric site on muscarinic receptors... - Interdomain communication in hepatitis C virus polymerase abolished by small molecule inhibitors bound to a novel allosteric siteStefania Di Marco
Istituto di Ricerche di Biologia Molecolare P. Angeletti, Pomezia (Rome, Italy
J Biol Chem 280:29765-70. 2005..Our structures identify a novel mechanism by which a new class of allosteric inhibitors inhibits the HCV polymerase and open the way to the development of novel antiviral agents against this clinically relevant human pathogen... - Intramolecular signaling pathways revealed by modeling anisotropic thermal diffusionNobuyuki Ota
Howard Hughes Medical Institute and Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94143-2240, USA
J Mol Biol 351:345-54. 2005..Therefore, the ATD method should prove to be a powerful and general complement to experimental efforts to understand the physical basis of intramolecular signaling... - Inhibition of the calcineurin-NFAT interaction by small organic molecules reflects binding at an allosteric siteSunghyun Kang
CBR Institute for Biomedical Research, Boston, MA 02115, USA
J Biol Chem 280:37698-706. 2005..The finding that an allosteric site controls NFAT binding opens new alternatives for inhibition of calcineurin-NFAT signaling. - A close structural analog of 2-methyl-6-(phenylethynyl)-pyridine acts as a neutral allosteric site ligand on metabotropic glutamate receptor subtype 5 and blocks the effects of multiple allosteric modulatorsAlice L Rodriguez
Department of Pharmacology and Program in Translational Neuropharmacology, Vanderbilt University Medical Center, 23rd Ave. South at Pierce, 417-D Preston Research Bldg, Nashville, Tennessee 37232-6600, USA
Mol Pharmacol 68:1793-802. 2005..The third compound, 5-methyl-6-(phenylethynyl)-pyridine (5MPEP), acts as a neutral allosteric site ligand that binds to the MPEP site and has no effects alone... - A selective metabotropic glutamate receptor 7 agonist: activation of receptor signaling via an allosteric site modulates stress parameters in vivoKayo Mitsukawa
Neuroscience Research, Novartis Institutes for BioMedical Research, Novartis Pharma AG, CH-4002 Basel, Switzerland
Proc Natl Acad Sci U S A 102:18712-7. 2005..dihydrochloride (AMN082), which directly activates receptor signaling via an allosteric site in the transmembrane domain... - Selective allosteric ligand activation of the retinoid X receptor heterodimers of NGFI-B and Nurr1Kentaro Morita
Graduate School of Frontier Biosciences, Osaka University, Osaka 565-0871, Japan
Biochem Pharmacol 71:98-107. 2005..The data indicate that the RXR heterodimers of NGFI-B and Nurr1 are selectively activated by the RXR ligand HX600, and that compounds such as HX600 will be valuable tools in investigating NGFI-B and Nurr1 function... - The number of catalytic elements is crucial for the emergence of metabolic coresIldefonso M De La Fuente
Department of Mathematics, Faculty of Science and Technology, University of the Basque Country, Vizcaya, Spain
PLoS ONE 4:e7510. 2009.... - Molecular dissection of Na+ binding to thrombinAgustin O Pineda
Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St Louis, Missouri 63110, USA
J Biol Chem 279:31842-53. 2004..The role of the water network uncovered in this study establishes a new paradigm for the allosteric regulation of thrombin and other Na(+)-activated enzymes involved in blood coagulation and the immune response... - ATP effects on insulin-degrading enzyme are mediated primarily through its triphosphate moietyEun Suk Song
Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, Kentucky 40536 0084, USA
J Biol Chem 279:54216-20. 2004..These data suggest the presence of an allosteric regulatory site on insulysin that may shift its specificity toward small peptide substrates... - Kinetic, mechanistic, and structural aspects of unliganded gating of acetylcholine receptor channels: a single-channel study of second transmembrane segment 12' mutantsC Grosman
Department of Physiology and Biophysics, State University of New York at Buffalo, Buffalo, New York 14214, USA
J Gen Physiol 115:621-35. 2000..Such increase is independent of the particular ligand used as the agonist, which suggests that these mutations affect mostly the isomerization step, having little, if any, effect on the ligand-affinity ratio... - A 3.0-A resolution study of nucleotide complexes with aspartate carbamoyltransferaseR B Honzatko
Proc Natl Acad Sci U S A 76:5105-9. 1979The binding sites of CTP, CDP, 5-BrCTP, and ATP to the allosteric site of aspartate carbamoyltransferase (carbamoylphosphate:L-aspartate carbamoyltransferase, EC 2.1.3... - ATP-regulated module (ARM) of the atrial natriuretic factor receptor guanylate cyclaseTeresa Duda
The Unit of Regulatory and Molecular Biology, Department of Cell Biology, SOM and NJMS, University of Medicine and Dentistry of New Jersey, Stratford, NJ 08084, USA
Peptides 26:969-84. 2005.... - Resolution of two substrate-binding sites in an engineered cytochrome P450eryF bearing a fluorescent probeDmitri R Davydov
Department of Pharmacology and Toxicology, The University of Texas Medical Branch, Galveston, Texas 77555 1031, USA
Biophys J 89:418-32. 2005..This transition is apparently associated with an important rearrangement of the system of salt links in the proximity of Cys-154... - Quantifying allosteric effects in proteinsDengming Ming
Computer and Computational Sciences Division, Los Alamos National Laboratory, Los Alamos, New Mexico 87545, USA
Proteins 59:697-707. 2005.... - Glucocorticoid receptor point mutation V571M facilitates coactivator and ligand binding by structural rearrangement and stabilizationPeter Carlsson
Department of Structural Biology, Karo Bio AB, Novum, S 141 57 Huddinge, Sweden
Mol Endocrinol 19:1960-77. 2005..This indicates that a reduction of the entropic cost for ligand binding may explain the increased affinity of V571M mutants for certain ligands... - Role of conformational heterogeneity in domain swapping and adapter function of the Cks proteinsMarkus A Seeliger
MRC Centre for Protein Engineering, University Chemical Laboratory, Lensfield Road, Cambridge CB2 1EW, United Kingdom
J Biol Chem 280:30448-59. 2005..We propose that the dynamic properties of the beta-sheet and its modification upon ligand binding underlie the domain swapping ability and the adapter function of Cks proteins... - Structure, function and interfacial allosterism in phospholipase A2: insight from the anion-assisted dimerBrian J Bahnson
Department of Chemistry and Biochemistry, University of Delaware, 312 Drake Hall, Newark, DE 19716, USA
Arch Biochem Biophys 433:96-106. 2005..Remarkably, the assisting water present in the activated complex is absent in this proPLA2 structure... - Structural signatures of the complex formed between 3-nitro-4-hydroxybenzoate and the Zn(II)-substituted R(6) insulin hexamerHelle Birk Olsen
Research and Development, Novo Nordisk A S, Bagsvaerd, Denmark
Protein Sci 12:1902-13. 2003..These results are consistent with coordination of the 3N4H carboxylate to the His B10 zinc ion and van der Waals interactions with Val B2, Asn B3, Leu B6, and Cys A7... - CBFbeta allosterically regulates the Runx1 Runt domain via a dynamic conformational equilibriumJiangli Yan
Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, Virginia 22906, USA
Nat Struct Mol Biol 11:901-6. 2004..Our results indicate that allosteric regulation by the CBFbeta subunit is mediated by a shift in an existing dynamic conformational equilibrium of both the Runt domain and DNA... - Visualizing induced fit in early assembly of the human signal recognition particleM A Rose
Department of Chemistry, University of North Carolina, Chapel Hill 27599-3290, USA
Nat Struct Biol 8:515-20. 2001..This mechanism illustrates principles general to ribonucleoprotein assembly reactions that rely on recruitment of architectural RNA binding proteins... - Monitoring the transition from the T to the R state in E.coli aspartate transcarbamoylase by X-ray crystallography: crystal structures of the E50A mutant enzyme in four distinct allosteric statesKimberly Stieglitz
Department of Chemistry, Merkert Chemistry Center, Boston College, Chestnut Hill, MA 02467, USA
J Mol Biol 341:853-68. 2004..They also suggest an explanation for diminished activity of the E50A enzyme and for the change in reaction mechanism from ordered to random for this mutant enzyme... - RIalpha subunit of PKA: a cAMP-free structure reveals a hydrophobic capping mechanism for docking cAMP into site BJian Wu
Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093, USA
Structure 12:1057-65. 2004..In the absence of cAMP, the "cap" is released via an extension of the C-terminal helix. This simple hinge mechanism for binding and release of cAMP also provides a mechanism for allosteric communication between sites A and B... - Allosteric inhibition of protein tyrosine phosphatase 1BChristian Wiesmann
Sunesis Pharmaceuticals, 341 Oyster Point Boulevard, South San Francisco, California 94080, USA
Nat Struct Mol Biol 11:730-7. 2004..Here we describe the discovery of an allosteric site in PTP1B... - Structure of nerve growth factor complexed with the shared neurotrophin receptor p75Xiao lin He
Departments of Microbiology and Immunology, and Structural Biology, Stanford University School of Medicine, Fairchild D319, 299 Campus Drive, Stanford, CA 94305 5124, USA
Science 304:870-5. 2004..Thus, neurotrophin signaling through p75 may occur by disassembly of p75 dimers and assembly of asymmetric 2:1 neurotrophin/p75 complexes, which could potentially engage a Trk receptor to form a trimolecular signaling complex... - Monitoring protein modification with allosteric ribozymesNarendra K Vaish
Sirna Therapeutics, Inc, 2950 Wilderness Place, Boulder, CO 80301, USA
Methods 32:428-36. 2004..These significant differences from antibodies allow the pre-programmed development of conformation-state-specific protein detection reagents that can be used to investigate the activation-state of signal transduction components... - Crystallographic studies on acyl ureas, a new class of glycogen phosphorylase inhibitors, as potential antidiabetic drugsNikos G Oikonomakos
Institute of Organic and Pharmaceutical Chemistry, The National Hellenic Research Foundation, Athens, Greece
Protein Sci 14:1760-71. 2005..Acyl ureas induce conformational changes in the vicinity of the allosteric site. Our findings suggest that acyl ureas inhibit glycogen phosphorylase by direct inhibition of AMP binding and .. - Structural basis for tumor pyruvate kinase M2 allosteric regulation and catalysisJill 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.... - Advances in glycogen phosphorylase inhibitor designNikos G Oikonomakos
National Hellenic Research Foundation, Institute of Organic and Pharmaceutical Chemistry, 48 Vassileos Constantinou Avenue, Athens 11635, Greece
Curr Opin Investig Drugs 9:379-95. 2008.... - Mechanism of corepressor-mediated specific DNA binding by the purine repressorM A Schumacher
Department of Biochemistry and Molecular Biology, Oregon Health Sciences University, Portland 97201 3098, USA
Cell 83:147-55. 1995.... - Plasticity of S2-S4 specificity pockets of executioner caspase-7 revealed by structural and kinetic analysisJohnson Agniswamy
Department of Biology, Molecular Basis of Disease, Georgia State University, Atlanta, GA 30302, USA
FEBS J 274:4752-65. 2007..These results should be considered in the design of selective small molecule inhibitors of this pharmacologically important protease... - Regulation of dCTP deaminase from Escherichia coli by nonallosteric dTTP binding to an inactive form of the enzymeEva Johansson
Centre for Crystallographic Studies, Department of Chemistry, University of Copenhagen, Denmark
FEBS J 274:4188-98. 2007..The dCTP deaminase then resembles a simple concerted system subjected to effector binding, but without the use of an allosteric site. - Naturally occurring pentacyclic triterpenes as inhibitors of glycogen phosphorylase: synthesis, structure-activity relationships, and X-ray crystallographic studiesXiaoan Wen
Center for Drug Discovery, College of Pharmacy, China Pharmaceutical University, 24 Tongjia Xiang, Nanjing 210009, China
J Med Chem 51:3540-54. 2008..Pentacyclic triterpenes represent a promising class of multiple-target antidiabetic agents that exert hypoglycemic effects, at least in part, through GP inhibition... - Nucleotide-dependent allostery within the ABC transporter ATP-binding cassette: a computational study of the MJ0796 dimerPeter M Jones
Department of Medical and Molecular Biosciences, Faculty of Science, University of Technology Sydney, P O Box 123, Broadway, New South Wales 2007, Australia
J Biol Chem 282:22793-803. 2007..The implications of these findings for the coupling of ATP hydrolysis to conformational changes in the transmembrane domains required for solute transport are discussed in light of recent whole transporter structures... - Structural and functional insights into the human Upf1 helicase coreZhihong Cheng
Laboratory of Macromolecular Structure, Institute of Molecular and Cell Biology, Singapore, Singapore
EMBO J 26:253-64. 2007..These conformational changes alter the likely ssRNA-binding channel in a manner that can explain how ATP binding destabilizes ssRNA binding to Upf1p... - Novel allosteric activation site in Escherichia coli fructose-1,6-bisphosphataseJustin K Hines
Department of Biochemistry, Biophysics, and Molecular Biology, Iowa State University, Ames, Iowa 50011, USA
J Biol Chem 281:18386-93. 2006.... - Transition from rolling to firm adhesion can be mimicked by extension of integrin alphaLbeta2 in an intermediate affinity stateAzucena Salas
CBR Institute for Biomedical Research, Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA
J Biol Chem 281:10876-82. 2006.... - Ionic contacts at DnaK substrate binding domain involved in the allosteric regulation of lid dynamicsVanesa Fernández-Sáiz
Unidad de Biofisica Consejo Superior de Investigaciones Cientificas Universidad del Pais Vasco, Euskal Herriko Unibertsitatea, 48080 Bilbao, Spain
J Biol Chem 281:7479-88. 2006..These interactions also stabilize peptide-Hsp70 complexes at physiological (37 degrees C) and stress (42 degrees C) temperatures, a requirement for productive substrate (re)folding... - Mechanistic insight into the allosteric activation of a ubiquitin-conjugating enzyme by RING-type ubiquitin ligasesEngin Ozkan
Department of Biochemistry and Pharmacology and Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, 6001 Forest Park Road, Dallas, TX 75390, USA
Proc Natl Acad Sci U S A 102:18890-5. 2005..Our studies reveal structural determinants for communication between distal functional sites of E2s and suggest that RING-type E3s activate E2s allosterically... - Molecular mechanisms of calmodulin's functional versatilityM Zhang
Department of Biochemistry, Hong Kong University of Science and Technology, Kowloon, People s Republic of China
Biochem Cell Biol 76:313-23. 1998..The binding of Ca2+ reduces the backbone flexibility of CaM. Formation of complexes with its target peptides further decreases the backbone motion of CaM... - Residues distant from the active site influence protein-tyrosine phosphatase 1B inhibitor bindingJacqueline Montalibet
Department of Biochemistry and Molecular Biology, Merck Frosst Center for Therapeutic Research, Pointe-Claire, Quebec H9R 4P8, Canada
J Biol Chem 281:5258-66. 2006.... - The crystal structure of methylglyoxal synthase from Escherichia coliD Saadat
Department of Biochemistry, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA
Structure 7:309-17. 1999.... - Structure of free fumarase C from Escherichia coliTodd Weaver
Department of Chemistry, University of Wisconsin La Crosse, 1725 State Street, 4020 Cowley Hall, La Crosse, Wisconsin 54601, USA
Acta Crystallogr D Biol Crystallogr 61:1395-401. 2005..This new crystallographic information suggests the use of water as a permanent member of the active site and the use of an imidazole-imidazolium conversion to control access at the allosteric B site... - Dynamic hysteresis in a one-dimensional Ising model: application to allosteric proteinsI Graham
Biophysics Group, Cavendish Laboratory, Madingley Road, Cambridge CB3 0HE, United Kingdom
Phys Rev E Stat Nonlin Soft Matter Phys 71:061923. 2005.... - Multidimensional NMR identifies the conformational shift essential for catalytic competence in the 60-kDa Drosophila melanogaster dUTPase trimerZsófia Dubrovay
Institute of Enzymology, Biological Research Center, Hungarian Academy of Sciences, POB 7, H 1518, Budapest, Hungary
J Biol Chem 279:17945-50. 2004..NMR titration of the enzyme with the nucleotide ligands as well as kinetic data indicated significant deviation from the model of independent active sites within the homotrimer. The results suggest allosterism in the eukaryotic dUTPase... - Crystal structure of the beta Ser178--> Pro mutant of tryptophan synthase. A "knock-out" allosteric enzymeMichael Weyand
Max Planck Institut fur molekulare Physiologie, Abteilung für Physikalische Biochemie, D 44227 Dortmund, Germany
J Biol Chem 277:10653-60. 2002..This effects the equilibrium between active and inactive conformations of the alpha-active site, altering k(cat) and K(m), and forms the structural basis for the missing allosteric communication between the alpha- and beta-subunits... - Allosteric alpha 1-adrenoreceptor antagonism by the conopeptide rho-TIAIain A Sharpe
Institute for Molecular Bioscience and the School of Biomedical Sciences, The University of Queensland, St. Lucia 4072, Queensland, Australia
J Biol Chem 278:34451-7. 2003.... - Structure and calcium-binding studies of a recoverin mutant (E85Q) in an allosteric intermediate stateJames B Ames
Center for Advanced Research in Biotechnology, University of Maryland Biotechnology Institute, Rockville, Maryland 20850, USA
Biochemistry 41:5776-87. 2002..We propose that Ca2+-bound myr-E85Q may represent a stable intermediate state in the kinetic mechanism of the calcium-myristoyl switch... - Dissection of the conduit for allosteric control of carbamoyl phosphate synthetase by ornithineOlivier A Pierrat
Department of Chemistry, Texas A and M University, College Station, Texas 77842-3012, USA
Arch Biochem Biophys 400:26-33. 2002..The mutants S792K and D1041A altered the allosteric regulation by ornithine and IMP in a similar way, suggesting common features in the activation mechanism exhibited by these two effectors...
Research Grants
- Structure and Function of CarboxypeptidasesRandal A Skidgel; Fiscal Year: 2010..Hypothesis: CPM enhances B1R function by binding to an allosteric site and substrate binding by CPM results in B1R conformational change and enhanced receptor activation...
- Mechanisms of Allosteric Influence on Enzymes ActivityGREGORY DUNCAN REINHART; Fiscal Year: 2011..These enzymes are homotetramers containing a single active site and a single allosteric site per subunit...
- Mechanisms of Allosteric Influence on Enzymes ActivityGREGORY DUNCAN REINHART; Fiscal Year: 2010..These enzymes are homotetramers containing a single active site and a single allosteric site per subunit...
- SULFATE ADENYLATION-BIOCHEMISTRY & ENZYMOLOGYThomas S Leyh; Fiscal Year: 2010..If EST is a half-site reactive enzyme, the non-catalytic active site might well function as the allosteric site of inhibition...
- Structural Investigation of Allosteric Regulation in Bacterial Carbonic AnhydraseJEFF CRONK; Fiscal Year: 2007..In view of its potential as a site for therapeutic intervention, the characterization of the allosteric site will be furthered by a virtual screen for potential non-substrate ligands...
- Molecular Mechanism of Allosteric Modulation of the Oxytocin Receptor by SterolsVADIM GENNADYEVICH CHEREZOV; Fiscal Year: 2010..hypothesis of this proposal is that cholesterol modulates the activity of the OXTR by binding to a distinct allosteric site(s) thus inducing a change in the receptor conformation...
- RESPONSES OF SUBPOPULATIONS OF MUSCARINIC RECEPTORSJohn Ellis; Fiscal Year: 2004..These tools include: pharmacological model testing, to determine whether ligands interact solely with an allosteric site and whether different allosteric ligands act at a common site; and, molecular genetic techniques, to ..
- ALLOSTERIC ENHANCEMENT OF ADENOSINE RECEPTORSJoel Linden; Fiscal Year: 2007..These compounds bind to an allosteric site on the receptor to increase the affinity of adenosine to the orthosteric site on the A1AR...
- Site-specific Allosteric Inhibitors for Inflammatory CaspasesJames A Wells; Fiscal Year: 2010..character of this approach permits one to target any site on the protein surface, whether active or allosteric site. This approach was used to identify specific inhibitors for caspase-1 that bind to a cysteine in a cavity ..
- Site-specific Allosteric Inhibitors for Inflammatory CaspasesJames Wells; Fiscal Year: 2007..character of this approach permits one to target any site on the protein surface, whether active or allosteric site. This approach was used to identify specific inhibitors for caspase-1 that bind to a cysteine in a cavity ..
- ALLOSTERIC ENHANCEMENT OF A1 ADENOSINE RECEPTORSJoel Linden; Fiscal Year: 1999..PD enhances agonist binding to purified H/F-A1 receptors, proving that it binds directly to an allosteric site on the receptor...
- The Mevalonate Pathway in StreptococcusTHOMAS LEYH; Fiscal Year: 2007..The mevalonate pathway is essential for survival of the organism in mouse lung. DPM and the allosteric site offer a lead compound and target that provide an opportunity to develop a new class of antibiotics that could ..
- The Mevalonate Pathway in StreptococcusThomas S Leyh; Fiscal Year: 2010..The mevalonate pathway is essential for survival of the organism in mouse lung. DPM and the allosteric site offer a lead compound and target that provide an opportunity to develop a new class of antibiotics that could ..
- Secretin Receptor Structure, Function and RegulationLaurence J Miller; Fiscal Year: 2010..detailed structural determinants for orthosteric agonists and antagonists, as well as to define the possible allosteric site of action of the endogenous agonist sequence within the receptor amino terminus...
- Secretin Receptor Structure, Function and RegulationLaurence J Miller; Fiscal Year: 2010..detailed structural determinants for orthosteric agonists and antagonists, as well as to define the possible allosteric site of action of the endogenous agonist sequence within the receptor amino terminus...
- Muscarinic receptor activators as novel antipsychotic agentsP Jeffrey Conn; Fiscal Year: 2010..Unlike agonists, these compounds do not directly activate the receptor but act at an allosteric site to potentiate the response to the endogenous agonist...
- ALLOSTERIC ENHANCEMENT OF ADENOSINE RECEPTORSJoel M Linden; Fiscal Year: 2009..These compounds bind to an allosteric site on the receptor to increase the affinity of adenosine to the orthosteric site on the A^R...
- Muscarinic receptor activators as novel antipsychotic agentsP Conn; Fiscal Year: 2009..Unlike agonists, these compounds do not directly activate the receptor but act at an allosteric site to potentiate the response to the endogenous agonist...
- Identifying allosteric inhibitors of caspasesJustin Scheer; Fiscal Year: 2005..of allosteric inhibition in caspase-1, and 3) identify natural regulators of caspases acting through the allosteric site. The studies are to include both caspase-1 and caspase-3...
- Functional and Inhibitory Studies of Human LipoxygenaseTHEODORE HOLMAN; Fiscal Year: 2005..three lipoxygenases affect their function?3) Over the past several years, we have proposed the presence of an allosteric site in both SLO and 15-HLO, which could be critical to the regulation of lipoxygenase activity, however its ..
- Mechanisms on Allosteric Influence on Enzymes ActivityGREGORY REINHART; Fiscal Year: 2006..These enzymes are homotetramers containing a single active site and a single allosteric site per subunit...
- Cheminformatics of Allosteric mGluR Modulation promotes Therapeutic DevelopmentJens Meiler; Fiscal Year: 2010..activity of mGluR5 potentiators observed in this HTS can be used to generate a pharmacophore of the mGluR5 allosteric site. This map of steric and electronic features necessary for optimal interaction of modulators with mGluR5 will ..
- MOLECULAR BASIS OF BLOOD COAGULATION REGULATIONSteven Olson; Fiscal Year: 2005..proteinases; ii) three basic residues of antithrombin are principally responsible for binding heparin at an allosteric site through an induced-fit mechanism and the action of these residues is coupled to global conformational changes ..
- Nitric Oxide Signaling and Soluble Guanylate CyclaseMICHAEL MARLETTA; Fiscal Year: 2007..of sGC, including the nature of the second NO binding site, 2) The characterization of the nucleotide allosteric site, including the role of this site in modulating NO activation of the enzyme, 3) The mapping of the (a) ..
- Kinetic Studies of Transcription ElongationDOROTHY ERIE; Fiscal Year: 2005..with the transition from the slow to the fast state being induced by binding of the templated NTP to the allosteric site. We hypothesize that this conformational switch is paramount to the regulation of transcription elongation ..