- An allosteric mechanism for activation of the kinase domain of epidermal growth factor receptor
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...
- 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...
- Structural basis for allosteric regulation of GPCRs by sodium ions
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...
- Ribonucleotide reductases
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...
- Targeting cancer with small molecule kinase inhibitors
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...
- 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...
- 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,..
- 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...
- 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...
- Detection of allosteric signal transmission by information-theoretic analysis of protein dynamics
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...
- 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
- ASD: a comprehensive database of allosteric proteins and modulators
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/...
- 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...
- 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...
- 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...
- Allostery wiring diagrams in the transitions that drive the GroEL reaction cycle
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...
- Allosteric transitions in biological nanomachines are described by robust normal modes of elastic networks
Physics Department, University at Buffalo, Buffalo, NY 14260, USA
Curr Protein Pept Sci 10:128-32. 2009
- 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...
- The origin of protein interactions and allostery in colocalization
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...
- Allosteric signal transmission in the nucleotide-binding domain of 70-kDa heat shock protein (Hsp70) molecular chaperones
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...
- Structural basis for allosteric regulation of the monomeric allosteric enzyme human glucokinase
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...
- Dissecting the role of 5'-AMP for allosteric stimulation, activation, and deactivation of AMP-activated protein kinase
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...
- 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...
- Allosteric communication in myosin V: from small conformational changes to large directed movements
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...
- Allosteric regulation of histidine kinases by their cognate response regulator determines cell fate
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...
- 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...
- Surface sites for engineering allosteric control in proteins
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...
- 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
- 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...
- 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...
- 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
- 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)...
- 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...
- Markov propagation of allosteric effects in biomolecular systems: application to GroEL-GroES
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...
- Intrinsic dynamics of enzymes in the unbound state and relation to allosteric regulation
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-..
- 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...
- 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...
- 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
- 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...
- Allosteric modulators of NR2B-containing NMDA receptors: molecular mechanisms and therapeutic potential
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...
- Structural changes involved in protein binding correlate with intrinsic motions of proteins in the unbound state
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
- 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
- Allosteric regulation of SERCA by phosphorylation-mediated conformational shift of phospholamban
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 ..
- 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...
- New concepts in drug discovery: collateral efficacy and permissive antagonism
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...
- Allostery and population shift in drug discovery
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...
- 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 ..
- Large-scale allosteric conformational transitions of adenylate kinase appear to involve a population-shift mechanism
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...
- On the conservation of the slow conformational dynamics within the amino acid kinase family: NAGK the paradigm
Department of Biological Chemistry and Molecular Modelling, IQAC CSIC, Barcelona, Spain
PLoS Comput Biol 6:e1000738. 2010
- Catalytic control in the EGF receptor and its connection to general kinase regulatory mechanisms
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...
- 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...
- 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...
- Computational modeling of allosteric communication reveals organizing principles of mutation-induced signaling in ABL and EGFR kinases
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...
- Allosteric regulation of Hsp70 chaperones by a proline switch
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...
- Allosteric regulation of glycogen synthase controls glycogen synthesis in muscle
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...
- 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...
- 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...
- 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...
- 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...
- 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...
- Structural basis for allostery in integrins and binding to fibrinogen-mimetic therapeutics
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 ..
- Predicting allosteric communication in myosin via a pathway of conserved residues
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)...
- 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...
- Coherent conformational degrees of freedom as a structural basis for allosteric communication
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...
- State-dependent cAMP binding to functioning HCN channels studied by patch-clamp fluorometry
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...
- Dynamic allostery: linkers are not merely flexible
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...
- Allosteric regulation of DNA cleavage and sequence-specificity through run-on oligomerization
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...
- Homotropic allosteric regulation in monomeric mammalian glucokinase
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 ..
- Rigor-like structures from muscle myosins reveal key mechanical elements in the transduction pathways of this allosteric motor
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...
- Unsuspected pathway of the allosteric transition in hemoglobin
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...
- 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
- A Monod-Wyman-Changeux mechanism can explain G protein-coupled receptor (GPCR) allosteric modulation
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...
- Structure-based prediction of protein-protein binding affinity with consideration of allosteric effect
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...
- NMR insights into protein allostery
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...
- Exploiting protein flexibility to predict the location of allosteric sites
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...
- 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 ..
- Allosteric opening of the polypeptide-binding site when an Hsp70 binds ATP
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. ..
- 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'...
- 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...
- 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...
- Allosteric regulation of nucleotidyl cyclases: an emerging pharmacological target
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...
- Stereoselective kinetics of warfarin binding to human serum albumin: effect of an allosteric interaction
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...
- 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...
- Allostery in a monomeric protein: the case of human serum albumin
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...
- 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...
- 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...
- Frequency and release flux of calcium sparks in rat cardiac myocytes: a relation to RYR gating
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...
- G protein coupled receptors as allosteric proteins and the role of allosteric modulators
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...
- Allosteric regulation of the transcription factor NFAT1 by multiple phosphorylation sites: a mathematical analysis
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...
- 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+]...
- Cooperative [Ca²+]-dependent regulation of the rate of myosin binding to actin: solution data and the tropomyosin chain model
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...
- Glycoprotein hormone receptors: link between receptor homodimerization and negative cooperativity
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...
- 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...
- 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...
- Allostery in the LacI/GalR family: variations on a theme
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...
- The anaerobic (class III) ribonucleotide reductase from Lactococcus lactis. Catalytic properties and allosteric regulation of the pure enzyme system
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...
- Allostery and cooperativity revisited
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...
- Entropy-driven cAMP-dependent allosteric control of inhibitory interactions in exchange proteins directly activated by cAMP
Department of Chemistry, Biochemistry, and Biomedical Sciences, McMaster University, Hamilton, Ontario L8S 4M1, Canada
J Biol Chem 283:19691-703. 2008
- Thermodynamics-based drug design: strategies for inhibiting protein-protein interactions
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...
- OMP peptides modulate the activity of DegS protease by differential binding to active and inactive conformations
Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
Mol Cell 33:64-74. 2009
- Ligand-induced conformational changes and conformational dynamics in the solution structure of the lactose repressor protein
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...