Genomes and Genes
Summary: A site on an enzyme which upon binding of a modulator, causes the enzyme to undergo a conformational change that may alter its catalytic or binding properties.
- Heitman L, Kleinau G, Brussee J, Krause G, Ijzerman A. Determination of different putative allosteric binding pockets at the lutropin receptor by using diverse drug-like low molecular weight ligands. Mol Cell Endocrinol. 2012;351:326-36 pubmed publisher..The present study showed that these compounds are useful tools to reveal details on different allosteric binding sites located within the 7TMD of the LHCGR. ..
- Valant C, Robert Lane J, Sexton P, Christopoulos A. The best of both worlds? Bitopic orthosteric/allosteric ligands of g protein-coupled receptors. Annu Rev Pharmacol Toxicol. 2012;52:153-78 pubmed publisher..Previously identified functionally selective compounds (and medicines) also may act via a bitopic mechanism, suggesting that the phenomenon is more widespread than currently appreciated. ..
- Berezov A, Cai Z, Freudenberg J, Zhang H, Cheng X, Thompson T, et al. Disabling the mitotic spindle and tumor growth by targeting a cavity-induced allosteric site of survivin. Oncogene. 2012;31:1938-48 pubmed publisher..Thus, the study validates a novel therapeutic target site in the survivin protein and provides a promising strategy to develop a new class of therapeutic small molecules for the treatment of human cancers. ..
- Prasannan C, Villar M, Artigues A, Fenton A. Identification of regions of rabbit muscle pyruvate kinase important for allosteric regulation by phenylalanine, detected by H/D exchange mass spectrometry. Biochemistry. 2013;52:1998-2006 pubmed publisher..The set of allosterically relevant peptides identified by this technique includes residues previously identified by mutagenesis to have roles in allosteric regulation by phenylalanine...
- Mirza A, Mustafa M, Talevich E, Kannan N. Co-conserved features associated with cis regulation of ErbB tyrosine kinases. PLoS ONE. 2010;5:e14310 pubmed publisher..Our analysis pinpoints key residues for mutational analysis, and provides new clues to cancer mutations that alter the canonical modes of ErbB kinase regulation. ..
- Mitternacht S, Berezovsky I. A geometry-based generic predictor for catalytic and allosteric sites. Protein Eng Des Sel. 2011;24:405-9 pubmed publisher..It is not biased towards typically catalytic residues, a property that is crucial when looking for non-catalytic effector sites, which are potent drug targets. ..
- Nussinov R, Tsai C. Allostery in disease and in drug discovery. Cell. 2013;153:293-305 pubmed publisher..We aim to increase the awareness of the linkage between disease symptoms on the cellular level and specific aberrant allosteric actions on the molecular level and to emphasize the potential of allosteric drugs in innovative therapies...
- Zhu L, Chen L, Zhou X, Zhang Y, Zhang Y, Zhao J, et al. Structural insights into the architecture and allostery of full-length AMP-activated protein kinase. Structure. 2011;19:515-22 pubmed publisher..These results not only make substantial revision to the current model of AMPK assembly, but also highlight a central role of the linker sequence of the ? subunit in mediating the allostery of AMPK. ..
- Huang Z, Zhu L, Cao Y, Wu G, Liu X, Chen Y, et al. ASD: a comprehensive database of allosteric proteins and modulators. Nucleic Acids Res. 2011;39:D663-9 pubmed publisher..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/. ..
- Huang W, Lu S, Huang Z, Liu X, Mou L, Luo Y, et al. Allosite: a method for predicting allosteric sites. Bioinformatics. 2013;29:2357-9 pubmed publisher..The Allosite server and tutorials are freely available at http://mdl.shsmu.edu.cn/AST CONTACT: firstname.lastname@example.org Supplementary data are available at Bioinformatics online. ..
- Jaffe E. Impact of quaternary structure dynamics on allosteric drug discovery. Curr Top Med Chem. 2013;13:55-63 pubmed..Also highlighted is the quaternary structure equilibrium of transthyretin and successful drug discovery efforts focused on controlling its quaternary structure dynamics. ..
- Ragnarsson L, Wang C, Andersson A, Fajarningsih D, Monks T, Brust A, et al. Conopeptide ?-TIA defines a new allosteric site on the extracellular surface of the ?1B-adrenoceptor. J Biol Chem. 2013;288:1814-27 pubmed publisher..1)-adrenergic receptor crystal structure, we modeled the ?(1B)-adrenoceptor (?(1B)-AR) to help identify the allosteric site for ?-conopeptide TIA, an inverse agonist at this receptor...
- Panjkovich A, Daura X. Exploiting protein flexibility to predict the location of allosteric sites. BMC Bioinformatics. 2012;13:273 pubmed publisher..Its performance has been demonstrated using a newly curated non-redundant set of 91 proteins with reported allosteric properties. The software developed in this work is available upon request from the authors. ..
- Burendahl S, Nilsson L. Computational studies of LXR molecular interactions reveal an allosteric communication pathway. Proteins. 2012;80:294-306 pubmed publisher..Thus, additional specificity between LXR? and its cofactors is likely to be found in molecular interactions outside the cofactor peptide or in other biological factors. ..
- Grant B, Lukman S, Hocker H, Sayyah J, Brown J, McCammon J, et al. Novel allosteric sites on Ras for lead generation. PLoS ONE. 2011;6:e25711 pubmed publisher..We thus propose that the predicted allosteric sites are viable targets for the development and optimization of new drugs. ..
- Elsinghorst P, Hartig W, Gündisch D, Mohr K, Tränkle C, Gutschow M. A hydrazide linker strategy for heterobivalent compounds as ortho- and allosteric ligands of acetylcholine-binding proteins. Curr Top Med Chem. 2011;11:2731-48 pubmed
- Sadowsky J, Burlingame M, Wolan D, McClendon C, Jacobson M, Wells J. Turning a protein kinase on or off from a single allosteric site via disulfide trapping. Proc Natl Acad Sci U S A. 2011;108:6056-61 pubmed publisher..we apply a site-directed technology, disulfide trapping, to interrogate structurally and functionally how an allosteric site on the Ser/Thr kinase, 3-phosphoinositide-dependent kinase 1 (PDK1)--the PDK1-interacting-fragment (PIF) ..
- Elber R. Simulations of allosteric transitions. Curr Opin Struct Biol. 2011;21:167-72 pubmed publisher..In the present review we examined different theoretical and computational attempts to solve the questions. ..
- Karagöz G, Duarte A, Ippel H, Uetrecht C, Sinnige T, van Rosmalen M, et al. N-terminal domain of human Hsp90 triggers binding to the cochaperone p23. Proc Natl Acad Sci U S A. 2011;108:580-5 pubmed publisher..We anticipate that our NMR approach has significant impact on future studies of full-length Hsp90 with cofactors and substrates, but also for the development of Hsp90 inhibiting anticancer drugs. ..
- Suratman S, Leach K, Sexton P, Felder C, Loiacono R, Christopoulos A. Impact of species variability and 'probe-dependence' on the detection and in vivo validation of allosteric modulation at the M4 muscarinic acetylcholine receptor. Br J Pharmacol. 2011;162:1659-70 pubmed publisher..This has implications for the validation of allosteric modulator actions in vivo. ..
- Mitternacht S, Berezovsky I. Coherent conformational degrees of freedom as a structural basis for allosteric communication. PLoS Comput Biol. 2011;7:e1002301 pubmed publisher..Leverage coupling can be calculated for any protein structure to analyze both biological and latent catalytic and regulatory sites. ..
- Li X, Chen Y, Lu S, Huang Z, Liu X, Wang Q, et al. Toward an understanding of the sequence and structural basis of allosteric proteins. J Mol Graph Model. 2013;40:30-9 pubmed publisher..These results may be of great significance in predicting which proteins are allosteric and in designing novel triggers to inhibit or activate proteins of interest. ..
- Namboodiri S, Giuliani A, Nair A, Dhar P. Looking for a sequence based allostery definition: a statistical journey at different resolution scales. J Theor Biol. 2012;304:211-8 pubmed publisher..These free-energy-transfer hydrophobicity-based RQA markers when evaluated by pattern recognition tools could distinguish allosteric proteins with 92% accuracy. ..
- Weinkam P, Pons J, Sali A. Structure-based model of allostery predicts coupling between distant sites. Proc Natl Acad Sci U S A. 2012;109:4875-80 pubmed publisherAllostery is a phenomenon that couples effector ligand binding at an allosteric site to a structural and/or dynamic change at a distant regulated site...
- Nussinov R, Tsai C. The different ways through which specificity works in orthosteric and allosteric drugs. Curr Pharm Des. 2012;18:1311-6 pubmed..We provide examples from functional in vivo scenarios for both types of cases, and suggest how high potency can be achieved in allosteric drug development. ..
- Henderson B, Orac C, Maciagiewicz I, Bergmeier S, McKay D. 3D-QSAR and 3D-QSSR models of negative allosteric modulators facilitate the design of a novel selective antagonist of human ?4?2 neuronal nicotinic acetylcholine receptors. Bioorg Med Chem Lett. 2012;22:1797-813 pubmed publisher..Additionally, information from the models presented in this work was used to synthesize novel molecules; which subsequently led to the discovery of a new selective antagonist of human ?4?2 nAChRs. ..
- Burford N, Watson J, Bertekap R, Alt A. Strategies for the identification of allosteric modulators of G-protein-coupled receptors. Biochem Pharmacol. 2011;81:691-702 pubmed publisher..This review is devoted to an examination of the strategies, challenges, and opportunities for high-throughput screening for allosteric modulators of GPCRs, with particular focus on the identification of positive allosteric modulators. ..
- Rodina A, Patel P, Kang Y, Patel Y, Baaklini I, Wong M, et al. Identification of an allosteric pocket on human hsp70 reveals a mode of inhibition of this therapeutically important protein. Chem Biol. 2013;20:1469-80 pubmed publisher..chemical tools for the study of human Hsp70, we developed a homology model that unveils a previously unknown allosteric site located in the nucleotide binding domain of Hsp70...
- Schipper J, MacKenzie S, Sharma A, Clark A. A bifunctional allosteric site in the dimer interface of procaspase-3. Biophys Chem. 2011;159:100-9 pubmed publisherThe dimer interface of caspase-3 contains a bifunctional allosteric site in which the enzyme can be activated or inactivated, depending on the context of the protein...
- Sidhu P, Liang A, Mehta A, Abdel Aziz M, Zhou Q, Desai U. Rational design of potent, small, synthetic allosteric inhibitors of thrombin. J Med Chem. 2011;54:5522-31 pubmed publisher..Overall, this work puts forward sulfated benzofurans as the first small, synthetic molecules as powerful lead compounds for the design of a new class of allosteric inhibitors of thrombin. ..
- Verghese J, Liang A, Sidhu P, Hindle M, Zhou Q, Desai U. First steps in the direction of synthetic, allosteric, direct inhibitors of thrombin and factor Xa. Bioorg Med Chem Lett. 2009;19:4126-9 pubmed publisher..The molecules represent the first allosteric small molecule inhibitors of the two enzymes. ..
- Tramontano E. The exploding field of the HCV polymerase non-nucleoside inhibitors: summary of a first generation compounds. Mini Rev Med Chem. 2008;8:1298-310 pubmed..All small molecules which have been identified to be selective non-nucleoside inhibitors (NNI) of the HCV RdRp to date are reported. ..
- Hardy J, Wells J. Dissecting an allosteric switch in caspase-7 using chemical and mutational probes. J Biol Chem. 2009;284:26063-9 pubmed publisher..We previously discovered small molecule thiol-containing inhibitors that when tethered revealed an allosteric site and trapped a conformation similar to the zymogen form of the enzyme...
- Ghosh A, Vishveshwara S. Variations in clique and community patterns in protein structures during allosteric communication: investigation of dynamically equilibrated structures of methionyl tRNA synthetase complexes. Biochemistry. 2008;47:11398-407 pubmed publisher..This ought to enhance our understanding of the functioning of aaRS in general. ..
- Matsumoto T, Kinoshita T, Kirii Y, Yokota K, Hamada K, Tada T. Crystal structures of MKK4 kinase domain reveal that substrate peptide binds to an allosteric site and induces an auto-inhibition state. Biochem Biophys Res Commun. 2010;400:369-73 pubmed publisher..These crystal structures revealed that the p38? peptide-bound npMKK4 at the allosteric site rather than at the putative substrate binding site and induced an auto-inhibition state...
- Hindie V, Stroba A, Zhang H, Lopez Garcia L, Idrissova L, Zeuzem S, et al. Structure and allosteric effects of low-molecular-weight activators on the protein kinase PDK1. Nat Chem Biol. 2009;5:758-64 pubmed publisher..Previous work described an allosteric site mediating phosphorylation-dependent activation of AGC kinases...
- Bonsor D, Hecht O, Vankemmelbeke M, Sharma A, Krachler A, Housden N, et al. Allosteric beta-propeller signalling in TolB and its manipulation by translocating colicins. EMBO J. 2009;28:2846-57 pubmed publisher..Comparison of the TolB mechanism to that of vertebrate guanine nucleotide exchange factor RCC1 suggests that allosteric signalling may be more prevalent in beta-propeller proteins than currently realized. ..
- Keov P, Sexton P, Christopoulos A. Allosteric modulation of G protein-coupled receptors: a pharmacological perspective. Neuropharmacology. 2011;60:24-35 pubmed publisher..The ever-expanding array of allosteric modulators arising from both academic and industrial research also highlights the need for the development of a uniform approach to nomenclature of such compounds. ..
- Daily M, Upadhyaya T, Gray J. Contact rearrangements form coupled networks from local motions in allosteric proteins. Proteins. 2008;71:455-66 pubmed..In summary, residue-residue contact rearrangement networks provide useful representations of the portions of allosteric pathways resulting from coupled local motions. ..
- Milne J, Lambert P, Schenk S, Carney D, Smith J, Gagne D, et al. Small molecule activators of SIRT1 as therapeutics for the treatment of type 2 diabetes. Nature. 2007;450:712-6 pubmed..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...
- Masterson L, Mascioni A, Traaseth N, Taylor S, Veglia G. Allosteric cooperativity in protein kinase A. Proc Natl Acad Sci U S A. 2008;105:506-11 pubmed publisher..Because protein kinase A is the prototype for the entire kinome, these findings may serve as a paradigm for describing long-range coupling in other protein kinases. ..
- Rowe B, Schaffhauser H, Morales S, Lubbers L, Bonnefous C, Kamenecka T, et al. Transposition of three amino acids transforms the human metabotropic glutamate receptor (mGluR)-3-positive allosteric modulation site to mGluR2, and additional characterization of the mGluR2-positive allosteric modulation site. J Pharmacol Exp Ther. 2008;326:240-51 pubmed publisher..In addition, we substituted Ser(688), Gly(689), and Asn(735) into hmGluR3 and created an active hmGluR2 allosteric modulation site on the hmGluR3 receptor. ..
- Cao H, Cao R, Zhang H, Zheng X, Gao D. Non-nucleoside inhibitors of NS5B polymerase binding to allosteric sites: 3D- QSAR and molecular docking studies. Curr Med Chem. 2008;15:1462-77 pubmed..0 software, positioned all of the inhibitors into the allosteric site to determine the probable binding conformation...
- Su D, Lim J, Tinney E, Wan B, Young M, Anderson K, et al. Substituted tetrahydroquinolines as potent allosteric inhibitors of reverse transcriptase and its key mutants. Bioorg Med Chem Lett. 2009;19:5119-23 pubmed publisher..The SAR optimization, mutation profiles, preparation of compounds, and pharmacokinetic profile of compounds are described. ..
- Beran R, Serebrov V, Pyle A. The serine protease domain of hepatitis C viral NS3 activates RNA helicase activity by promoting the binding of RNA substrate. J Biol Chem. 2007;282:34913-20 pubmed