Protein activity regulation by conformational entropy
Abstract
How the interplay between protein structure and internal dynamics regulates protein function is poorly understood. Often, ligand binding, post-translational modifications and mutations modify protein activity in a manner that is not possible to rationalize solely on the basis of structural data. It is likely that changes in the internal motions of proteins have a major role in regulating protein activity, but the nature of their contributions remains elusive, especially in quantitative terms. Here we show that changes in conformational entropy can determine whether protein-ligand interactions will occur, even among protein complexes with identical binding interfaces. We have used NMR spectroscopy to determine the changes in structure and internal dynamics that are elicited by the binding of DNA to several variants of the catabolite activator protein (CAP) that differentially populate the inactive and active DNA-binding domain states. We found that the CAP variants have markedly different affinities for DNA, despite the CAP−DNA-binding interfaces being essentially identical in the various complexes. Combined with thermodynamic data, the results show that conformational entropy changes can inhibit the binding of CAP variants that are structurally poised for optimal DNA binding or can stimulate the binding activity of CAP variants that only transiently populate the DNA-binding-domain active state. Collectively, the data show how changes in fast internal dynamics (conformational…
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The observed changes in protein conformations and dynamics may alter protein activity.
“suggest that the observed changes in protein conformations and dynamics may alter protein activity [61].”
Cites
Dynamic personalities of proteins
Henzler-Wildman, K., & Kern, D. (2007) · Nature · doi:10.1038/nature06522 · Cited by 2,545 · see citing works
The role of dynamic conformational ensembles in biomolecular recognition
Boehr, D. D., Nussinov, R., & Wright, P. E. (2009) · Nature Chemical Biology · doi:10.1038/nchembio.232 · Cited by 2,008 · see citing works
Win some, lose some: enthalpy-entropy compensation in weak intermolecular interactions
Dunitz, J. D. (1995) · Chemistry & Biology · doi:10.1016/1074-5521(95)90097-7 · Cited by 669 · see citing works
Conformational entropy in molecular recognition by proteins
Frederick, K. K., Marlow, M. S., Valentine, K. G., & Wand, A. J. (2007) · Nature · doi:10.1038/nature05959 · Cited by 663 · see citing works
Dynamically driven protein allostery
Popovych, N., Sun, S., Ebright, R. H., & Kalodimos, C. G. (2006) · Nature Structural & Molecular Biology · doi:10.1038/nsmb1132 · Cited by 637 · see citing works
Two-State Allosteric Behavior in a Single-Domain Signaling Protein
Volkman, B. F., Lipson, D., Wemmer, D. E., & Kern, D. (2001) · Science · doi:10.1126/science.291.5512.2429 · Cited by 594 · see citing works
Binding of Small-Molecule Ligands to Proteins: “What You See” Is Not Always “What You Get”
Mobley, D., & Dill, K. (2009) · Structure · doi:10.1016/j.str.2009.02.010 · Cited by 569 · see citing works
Ishima, R., & Torchia, D. A. (2000) · Nature Structural Biology · doi:10.1038/78963 · Cited by 529 · see citing works
Yang, D., & Kay, L. E. (1996) · Journal of Molecular Biology · doi:10.1006/jmbi.1996.0581 · Cited by 459 · see citing works
NMR spectroscopy brings invisible protein states into focus
Baldwin, A. J., & Kay, L. E. (2009) · Nature Chemical Biology · doi:10.1038/nchembio.238 · Cited by 432 · see citing works
Dynamic activation of an allosteric regulatory protein
Tzeng, S., & Kalodimos, C. G. (2009) · Nature · doi:10.1038/nature08560 · Cited by 378 · see citing works
Self-citationAkke, M., Brueschweiler, R., & Palmer, A. G. I. (1993) · Journal of the American Chemical Society · doi:10.1021/ja00074a073 · Cited by 356 · see citing works
Hidden dynamic allostery in a PDZ domain
Petit, C. M., Zhang, J., Sapienza, P. J., Fuentes, E. J., & Lee, A. L. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0904492106 · Cited by 344 · see citing works
Catabolite activator protein: DNA binding and transcription activation
Lawson, C. L., David Swigon, A., Murakami, K. S., Darst, S. A., Berman, H. M., & Ebright, R. H. (2004) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2004.01.012 · Cited by 330 · see citing works
Solution structure of a minor and transiently formed state of a T4 lysozyme mutant
Bouvignies, G., Vallurupalli, P., Hansen, D. F., Correia, B. E., Lange, O. F., Bah, A., Vernon, R. M., Dahlquist, F. W., Baker, D. A., & Kay, L. E. (2011) · Nature · doi:10.1038/nature10349 · Cited by 301 · see citing works
Dynamic activation of protein function: a view emerging from NMR spectroscopy.
Wand, A. J. (2001) · Nature Structural Biology · doi:10.1038/nsb1101-926 · Cited by 299 · see citing works
Protein dynamics and allostery: an NMR view
Tzeng, S., & Kalodimos, C. G. (2010) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2010.10.007 · Cited by 256 · see citing works
Self-citationThe role of conformational entropy in molecular recognition by calmodulin
Marlow, M. S., Dogan, J., Frederick, K. K., Valentine, K. G., & Wand, A. J. (2010) · Nature Chemical Biology · doi:10.1038/nchembio.347 · Cited by 251 · see citing works
A Direct Measure of the Contribution of Solvent Reorganization to the Enthalpy of Binding
Chervenak, M. C., & Toone, E. J. (1994) · Journal of the American Chemical Society · doi:10.1021/ja00102a021 · Cited by 234 · see citing works
Structural basis for cAMP-mediated allosteric control of the catabolite activator protein
Popovych, N., Tzeng, S., Tonelli, M., Ebright, R. H., & Kalodimos, C. G. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0900595106 · Cited by 218 · see citing works
Self-citationInsights into the local residual entropy of proteins provided by NMR relaxation
Li, Z., Raychaudhuri, S., & Wand, A. J. (1996) · Protein Science · doi:10.1002/pro.5560051228 · Cited by 210 · see citing works
Molecular Recognition by Induced Fit: How Fit is the Concept?
Bosshard, H. R. (2001) · Physiology · doi:10.1152/physiologyonline.2001.16.4.171 · Cited by 184 · see citing works
Extent of enthalpy–entropy compensation in protein–ligand interactions
Olsson, T. S. G., Ladbury, J. E., Pitt, W. R., & Williams, M. A. (2011) · Protein Science · doi:10.1002/pro.692 · Cited by 171 · see citing works
Estimation of the available free energy in a LOV2-Jα photoswitch
Yao, X., Rosen, M. K., & Gardner, K. H. (2008) · Nature Chemical Biology · doi:10.1038/nchembio.99 · Cited by 163 · see citing works
Palmer, A. G. I., Grey, M. J., & Wang, C. (2005) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(05)94018-4 · Cited by 99 · see citing works
Internal dynamics control activation and activity of the autoinhibited Vav DH domain
Li, P., Martins, I., Amarasinghe, G. K., & Rosen, M. K. (2008) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.1428 · Cited by 99 · see citing works
Using NMR to study fast dynamics in proteins: methods and applications
Sapienza, P. J., & Lee, A. L. (2010) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2010.09.006 · Cited by 92 · see citing works
Conformational dynamics and thermodynamics of protein–ligand binding studied by NMR relaxation
Akke, M. (2012) · Biochemical Society Transactions · doi:10.1042/bst20110750 · Cited by 62 · see citing works
Gekko, K., Obu, N., Li, J., & Lee, J. C. (2004) · Biochemistry · doi:10.1021/bi036271e · Cited by 58 · see citing works
Youn, H., Koh, J., & Roberts, G. P. (2008) · Journal of Bacteriology · doi:10.1128/jb.00074-08 · Cited by 22 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
The ensemble nature of allostery
Motlagh, H. N., Wrabl, J. O., Li, J., & Hilser, V. J. (2014) · Nature · doi:10.1038/nature13001 · Cited by 1,247 · see citing works
Entropy-Enthalpy Compensation: Role and Ramifications in Biomolecular Ligand Recognition and Design
Chodera, J. D., & Mobley, D. L. (2013) · Annual Review of Biophysics · doi:10.1146/annurev-biophys-083012-130318 · Cited by 531 · see citing works
The Role of Protein Loops and Linkers in Conformational Dynamics and Allostery
Papaleo, E., Saladino, G., Lambrughi, M., Lindorff‐Larsen, K., Gervasio, F. L., & Nussinov, R. (2016) · Chemical Reviews · doi:10.1021/acs.chemrev.5b00623 · Cited by 426 · see citing works
Power of Biocatalysis for Organic Synthesis
Winkler, C. K., Schrittwieser, J. H., & Kroutil, W. (2021) · ACS Central Science · doi:10.1021/acscentsci.0c01496 · Cited by 396 · see citing works
Protein conformational flexibility modulates kinetics and thermodynamics of drug binding
Amaral, M., Kokh, D. B., Bomke, J., Wegener, A. A., Buchstaller, H., Eggenweiler, H., Matias, P. M., Sirrenberg, C., Wade, R. C., & Frech, M. (2017) · Nature Communications · doi:10.1038/s41467-017-02258-w · Cited by 293 · see citing works
Structural basis for protein antiaggregation activity of the trigger factor chaperone.
Saio, T., Guan, X., Rossi, P., Economou, A., & Kalodimos, C. G. (2014) · Science · doi:10.1126/science.1250494 · Cited by 289 · see citing works
Self-citationDavies, D. R., Gelinas, A. D., Zhang, C., Rohloff, J. C., Carter, J. D., O’Connell, D., Waugh, S. M., Wolk, S. K., Mayfield, W. S., Burgin, A. B., et al. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1213933109 · Cited by 257 · see citing works
Integrative, dynamic structural biology at atomic resolution—it's about time
Bedem, H. V. D., & Fraser, J. S. (2015) · Nature Methods · doi:10.1038/nmeth.3324 · Cited by 246 · see citing works
Liu, X. R., Zhang, M. M., & Gross, M. L. (2020) · Chemical Reviews · doi:10.1021/acs.chemrev.9b00815 · Cited by 241 · see citing works
NMR spectroscopy captures the essential role of dynamics in regulating biomolecular function
Alderson, T. R., & Kay, L. E. (2021) · Cell · doi:10.1016/j.cell.2020.12.034 · Cited by 227 · see citing works
The Molecular Origin of Enthalpy/Entropy Compensation in Biomolecular Recognition
Fox, J. M., Zhao, M., Fink, M. J., Kang, K., & Whitesides, G. M. (2018) · Annual Review of Biophysics · doi:10.1146/annurev-biophys-070816-033743 · Cited by 211 · see citing works
The role of dimer asymmetry and protomer dynamics in enzyme catalysis
Kim, T. H., Mehrabi, P., Ren, Z. M., Sljoka, A., Ing, C. E., Bezginov, A., Ye, L., Pomès, R., Prosser, R. S., & PAI, E. F. (2017) · Science · doi:10.1126/science.aag2355 · Cited by 199 · see citing works
Cooperativity Principles in Self-Assembled Nanomedicine
Li, Y., Wang, Y., Huang, G., & Gao, J. (2018) · Chemical Reviews · doi:10.1021/acs.chemrev.8b00195 · Cited by 191 · see citing works
Entropy in molecular recognition by proteins
Caro, J. A., Harpole, K. W., Kasinath, V., Lim, J., Granja, J. M., Valentine, K. G., Sharp, K. A., & Wand, A. J. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1621154114 · Cited by 187 · see citing works
50 years of allosteric interactions: the twists and turns of the models
Changeux, J. (2013) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3695 · Cited by 177 · see citing works
Allosteric Modulator Discovery: From Serendipity to Structure-Based Design
Lu, S., He, X., Ni, D., & Zhang, J. (2019) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.8b01749 · Cited by 176 · see citing works
Wand, A. J. (2012) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2012.11.005 · Cited by 173 · see citing works
The structural basis of T-cell receptor (TCR) activation: An enduring enigma
Mariuzza, R. A., Agnihotri, P., & Orban, J. P. (2020) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)49904-2 · Cited by 171 · see citing works
Ras activation by SOS: Allosteric regulation by altered fluctuation dynamics
Iversen, L., Tu, H.-L., Lin, W.-C., Christensen, S. M., Abel, S. M., Iwig, J., Wu, H.-J., Gureasko, J., Rhodes, C., Petit, R. S., et al. (2014) · Science · doi:10.1126/science.1250373 · Cited by 154 · see citing works
Enthalpy–entropy compensation: the role of solvation
Dragan, A. I., Read, C. M., & Crane‐Robinson, C. (2016) · European Biophysics Journal · doi:10.1007/s00249-016-1182-6 · Cited by 150 · see citing works
Controlling entropy to tune the functions of intrinsically disordered regions
Flock, T., Weatheritt, R. J., Latysheva, N. S., & Babu, M. M. (2014) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2014.05.007 · Cited by 146 · see citing works
Interplay between Conformational Entropy and Solvation Entropy in Protein–Ligand Binding
Verteramo, M. L., Stenström, O., Ignjatović, M. M., Caldararu, O. F., Olsson, M. A., Manzoni, F., Leffler, H., Oksanen, E., Logan, D. T., Nilsson, U. J., et al. (2019) · Journal of the American Chemical Society · doi:10.1021/jacs.8b11099 · Cited by 149 · see citing works
Harnessing Allostery: A Novel Approach to Drug Discovery
Lu, S., Li, S., & Zhang, J. (2014) · Medicinal Research Reviews · doi:10.1002/med.21317 · Cited by 146 · see citing works
Allosteric sites: remote control in regulation of protein activity
Guarnera, E., & Berezovsky, I. N. (2015) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2015.10.004 · Cited by 149 · see citing works
Proteasome allostery as a population shift between interchanging conformers
Ruschak, A. M., & Kay, L. E. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1213640109 · Cited by 140 · see citing works
Kastritis, P., Rodrigues, J., Folkers, G., Boelens, R., & Bonvin, A. (2014) · Journal of Molecular Biology · doi:10.1016/j.jmb.2014.04.017 · Cited by 137 · see citing works
Microscopic Insights into the NMR Relaxation-Based Protein Conformational Entropy Meter
Kasinath, V., Sharp, K. A., & Wand, A. J. (2013) · Journal of the American Chemical Society · doi:10.1021/ja405200u · Cited by 133 · see citing works
Molten globules, entropy-driven conformational change and protein folding
Baldwin, R. L., & Rose, G. D. (2012) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2012.11.004 · Cited by 130 · see citing works
Solution NMR Spectroscopy for the Study of Enzyme Allostery
Lisi, G. P., & Loria, J. P. (2016) · Chemical Reviews · doi:10.1021/acs.chemrev.5b00541 · Cited by 127 · see citing works
Single-molecule FRET methods to study the dynamics of proteins at work
Mazal, H., & Haran, G. (2019) · Current Opinion in Biomedical Engineering · doi:10.1016/j.cobme.2019.08.007 · Cited by 130 · see citing works
Allosteric Motions of the CRISPR–Cas9 HNH Nuclease Probed by NMR and Molecular Dynamics
East, K. W., Newton, J. C., Morzan, U. N., Narkhede, Y. B., Acharya, A., Skeens, E., Jogl, G., Batista, V. S., Palermo, G., & Lisi, G. P. (2019) · Journal of the American Chemical Society · doi:10.1021/jacs.9b10521 · Cited by 122 · see citing works
Green, J. D., Stapleton, M. R., Smith, L. J., Artymiuk, P. J., Kahramanoglou, C., Hunt, D. M., & Buxton, R. S. (2014) · Current Opinion in Microbiology · doi:10.1016/j.mib.2014.01.003 · Cited by 124 · see citing works
Fenley, A. T., Muddana, H. S., & Gilson, M. (2012) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.1213180109 · Cited by 122 · see citing works
Choy, M. S., Li, Y., Machado, L. E. S. F., Kunze, M. B. A., Connors, C. R., Wei, X., Lindorff‐Larsen, K., Page, R., & Peti, W. (2017) · Molecular Cell · doi:10.1016/j.molcel.2017.01.014 · Cited by 123 · see citing works
Unraveling structural mechanisms of allosteric drug action
Nussinov, R., & Tsai, C.-J. (2014) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2014.03.006 · Cited by 119 · see citing works
Baxa, M. C., Haddadian, E. J., Jumper, J., Freed, K. F., & Sosnick, T. R. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1407768111 · Cited by 119 · see citing works
Ye, G., Zhu, L., Ma, Y., He, M., Zheng, C., Shen, K., Hong, X., Xiao, Z., Jia, Y., Gao, P., et al. (2024) · Journal of the American Chemical Society · doi:10.1021/jacs.4c09062 · Cited by 112 · see citing works
Ligand binding remodels protein side-chain conformational heterogeneity
Wankowicz, S. A. M., de Oliveira, S. H. P., Hogan, D. W., Bedem, H. V. D., & Fraser, J. S. (2022) · eLife · doi:10.7554/elife.74114 · Cited by 110 · see citing works
Measuring Entropy in Molecular Recognition by Proteins
Wand, A. J., & Sharp, K. A. (2018) · Annual Review of Biophysics · doi:10.1146/annurev-biophys-060414-034042 · Cited by 108 · see citing works
Probing the diverse landscape of protein flexibility and binding
Marsh, J. A., Teichmann, S. A., & Forman-Kay, J. D. (2012) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2012.08.008 · Cited by 107 · see citing works
Integrated Computational Approaches and Tools for Allosteric Drug Discovery
Amamuddy, O. S., Veldman, W., Manyumwa, C. V., Khairallah, A., Agajanian, S., Odeyemi, O., Verkhivker, G. M., & Bishop, Ö. T. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21030847 · Cited by 105 · see citing works
Naganathan, A. N. (2018) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2018.09.004 · Cited by 103 · see citing works
Symmetry, Rigidity, and Allosteric Signaling: From Monomeric Proteins to Molecular Machines
Thirumalai, D., Hyeon, C., Zhuravlev, P. I., & Lorimer, G. H. (2019) · Chemical Reviews · doi:10.1021/acs.chemrev.8b00760 · Cited by 105 · see citing works
Signaling through dynamic linkers as revealed by PKA
Akimoto, M., Selvaratnam, R., McNicholl, E. T., Verma, G., Taylor, S. S., & Melacini, G. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1312644110 · Cited by 104 · see citing works
The structural basis of T-cell receptor (TCR) activation: An enduring enigma
Mariuzza, R. A., Agnihotri, P., & Orban, J. P. (2019) · Journal of Biological Chemistry · doi:10.1074/jbc.rev119.009411 · Cited by 104 · see citing works
Predictions of entropy for diatomic molecules and gaseous substances
Jia, C., Wang, C.-W., Zhang, L., Peng, X., Tang, H., Liu, J., Xiong, Y., & Zeng, R. (2017) · Chemical Physics Letters · doi:10.1016/j.cplett.2017.12.013 · Cited by 103 · see citing works
How do regulatory networks evolve and expand throughout evolution?
Voordeckers, K., Pougach, K., & Verstrepen, K. J. (2015) · Current Opinion in Biotechnology · doi:10.1016/j.copbio.2015.02.001 · Cited by 99 · see citing works
Fluctuations of Electric Fields in the Active Site of the Enzyme Ketosteroid Isomerase
Welborn, V. V., & Head-Gordon, T. L. (2019) · Journal of the American Chemical Society · doi:10.1021/jacs.9b05323 · Cited by 102 · see citing works
Conformational stabilization of ubiquitin yields potent and selective inhibitors of USP7
Zhang, Y., Zhou, L., Rougé, L., Phillips, A. H., Lam, C., Liu, P., Sandoval, W. N., Helgason, E., Murray, J. M., Wertz, I. E., et al. (2012) · Nature Chemical Biology · doi:10.1038/nchembio.1134 · Cited by 102 · see citing works
Allosteric inhibition through suppression of transient conformational states
Tzeng, S., & Kalodimos, C. G. (2013) · Nature Chemical Biology · doi:10.1038/nchembio.1250 · Cited by 101 · see citing works
Self-citationLi, J., White, J. T., Saavedra, H. G., Wrabl, J. O., Motlagh, H. N., Liu, K., Sowers, J. R., Schroer, T. A., Thompson, E. B., & Hilser, V. J. (2017) · eLife · doi:10.7554/elife.30688 · Cited by 98 · see citing works
Beaver, S. K., Mesa‐Torres, N., Pey, A. L., & Timson, D. J. (2019) · Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics · doi:10.1016/j.bbapap.2019.05.002 · Cited by 97 · see citing works
Entropy redistribution controls allostery in a metalloregulatory protein
Capdevila, D. A., Braymer, J. J., Edmonds, K. A., Wu, H., & Giedroc, D. P. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1620665114 · Cited by 96 · see citing works
Structures of Large Protein Complexes Determined by Nuclear Magnetic Resonance Spectroscopy
Huang, C., & Kalodimos, C. G. (2017) · Annual Review of Biophysics · doi:10.1146/annurev-biophys-070816-033701 · Cited by 96 · see citing works
Pantsar, T., Rissanen, S., Dauch, D., Laitinen, T., Vattulainen, I., & Poso, A. (2018) · PLOS Computational Biology · doi:10.1371/journal.pcbi.1006458 · Cited by 85 · see citing works
Advances in NMR Methods To Map Allosteric Sites: From Models to Translation
Boulton, S., & Melacini, G. (2016) · Chemical Reviews · doi:10.1021/acs.chemrev.5b00718 · Cited by 89 · see citing works
Ligand modulation of sidechain dynamics in a wild-type human GPCR
Clark, L. D., Dikiy, I., Chapman, K., Rödström, K. E. J., Aramini, J. M., Levine, M. V., Khelashvili, G., Rasmussen, S. G. F., Gardner, K. H., & Rosenbaum, D. M. (2017) · eLife · doi:10.7554/elife.28505 · Cited by 91 · see citing works
Blacklock, K. M., & Verkhivker, G. M. (2014) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1003679 · Cited by 90 · see citing works
Dynamic allostery governs cyclophilin A–HIV capsid interplay
Lu, M., Hou, G., Zhang, H., Suiter, C. L., Ahn, J., Byeon, I. L., Perilla, J. R., LANGMEAD, C. J., Hung, I., Gor’kov, P. L., et al. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1516920112 · Cited by 88 · see citing works
Lisi, G. P., & Loria, J. P. (2017) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2017.08.002 · Cited by 88 · see citing works
Computer Simulations of Intrinsically Disordered Proteins
Chong, S., Chatterjee, P., & Ham, S. (2017) · Annual Review of Physical Chemistry · doi:10.1146/annurev-physchem-052516-050843 · Cited by 84 · see citing works
Structural biology of supramolecular assemblies by magic-angle spinning NMR spectroscopy
Quinn, C. M., & Polenova, T. E. (2017) · Quarterly Reviews of Biophysics · doi:10.1017/s0033583516000159 · Cited by 86 · see citing works
Correlating structure and energetics in protein-ligand interactions: paradigms and paradoxes.
Martin, S., & Clements, J. H. (2013) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-060410-105819 · Cited by 85 · see citing works
Emerging Themes in PDZ Domain Signaling
Liu, X., & Fuentes, E. J. (2018) · International review of cytology · doi:10.1016/bs.ircmb.2018.05.013 · Cited by 83 · see citing works
Deciphering the Allosterically Driven Conformational Ensemble in Tryptophan Synthase Evolution
Maria‐Solano, M. A., Iglesias‐Fernández, J., & Osuna, S. (2019) · Journal of the American Chemical Society · doi:10.1021/jacs.9b03646 · Cited by 83 · see citing works
Pandey, S., Calvey, G. D., Katz, A. M., Malla, T. N., Koua, F., Martin-Garcia, J. M., Poudyal, I., Yang, J.-H., Vakili, M., Yefanov, O. M., et al. (2021) · IUCrJ · doi:10.1107/s2052252521008125 · Cited by 79 · see citing works
Intramolecular Fuzzy Interactions Involving Intrinsically Disordered Domains
Arbesú, M., Iruela, G., Fuentes, H., Teixeira, J. M. C., & Pons, M. (2018) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2018.00039 · Cited by 79 · see citing works
NMR Methods to Study Dynamic Allostery
Grutsch, S., Brüschweiler, S., & Tollinger, M. (2016) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1004620 · Cited by 78 · see citing works
Population Shuffling of Protein Conformations
Smith, C. A., Ban, D., Pratihar, S., Giller, K., Schwiegk, C., de Groot, B. L., Becker, S., Griesinger, C., & Lee, D. (2014) · Angewandte Chemie International Edition · doi:10.1002/anie.201408890 · Cited by 77 · see citing works
Wang, J., Wei, Y., Hu, X., Fang, Y., Li, X., Liu, J., Wang, S., & Yuan, Q. (2015) · Journal of the American Chemical Society · doi:10.1021/jacs.5b04894 · Cited by 76 · see citing works
Rodgers, T. L., Townsend, P. D., Burnell, D., Jones, M. L., Richards, S. A., McLeish, T. C. B., Pohl, E., Wilson, M. R., & Cann, M. J. (2013) · PLoS Biology · doi:10.1371/journal.pbio.1001651 · Cited by 75 · see citing works
Design of protein switches based on an ensemble model of allostery
Choi, J. H., Laurent, A. H., Hilser, V. J., & Ostermeier, M. (2015) · Nature Communications · doi:10.1038/ncomms7968 · Cited by 74 · see citing works
Non‐covalent Single Transcription Factor Encapsulation Inside a DNA Cage
Crawford, R., Erben, C. M., Periz, J., Hall, L. M., Brown, T. P., Turberfield, A. J., & Kapanidis, A. N. (2013) · Angewandte Chemie International Edition · doi:10.1002/anie.201207914 · Cited by 73 · see citing works
The immune checkpoint receptor LAG3: Structure, function, and target for cancer immunotherapy
Mariuzza, R. A., Shahid, S., & Karade, S. S. (2024) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2024.107241 · Cited by 72 · see citing works
Dias, D. M. G., & Ciulli, A. (2014) · Progress in Biophysics and Molecular Biology · doi:10.1016/j.pbiomolbio.2014.08.012 · Cited by 71 · see citing works
Small-Molecule-Triggered and Light-Controlled Reversible Regulation of Enzymatic Activity
Tian, T., Song, Y., Wang, J., Fu, B., He, Z., Xu, X., Li, A., Zhou, X. H., Wang, S., & Zhou, X. (2016) · Journal of the American Chemical Society · doi:10.1021/jacs.5b11532 · Cited by 69 · see citing works
On the relationship between NMR-derived amide order parameters and protein backbone entropy changes
Sharp, K. A., O’Brien, E. S., Kasinath, V., & Wand, A. J. (2015) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.24789 · Cited by 68 · see citing works
Computational Methods for Configurational Entropy Using Internal and Cartesian Coordinates
Hikiri, S., Yoshidome, T., & Ikeguchi, M. (2016) · Journal of Chemical Theory and Computation · doi:10.1021/acs.jctc.6b00563 · Cited by 68 · see citing works
Singh, S., & Bowman, G. R. (2017) · Journal of Chemical Theory and Computation · doi:10.1021/acs.jctc.6b01181 · Cited by 67 · see citing works
Brüschweiler, S., Konrat, R., & Tollinger, M. (2013) · ACS Chemical Biology · doi:10.1021/cb4002188 · Cited by 67 · see citing works
Probing the Dynamic Distribution of Bound States for Methylcytosine-binding Domains on DNA
Cramer, J. M., Scarsdale, J. N., Walavalkar, N. M., Buchwald, W. A., Ginder, G. D., & Williams, D. C. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.512236 · Cited by 66 · see citing works
Cembran, A., Kim, J., Gao, J., & Veglia, G. (2014) · Physical Chemistry Chemical Physics · doi:10.1039/c4cp00110a · Cited by 62 · see citing works
Fulyani, F., Schuurman‐Wolters, G. K., Žagar, A. V., Guskov, A., Slotboom, D. J., & Poolman, B. (2013) · Structure · doi:10.1016/j.str.2013.07.020 · Cited by 65 · see citing works
Directional Selection Precedes Conformational Selection in Ubiquitin–UIM Binding
Long, D., & Brüschweiler, R. (2013) · Angewandte Chemie · doi:10.1002/ange.201208683 · Cited by 65 · see citing works
Allosteric Regulation Points Control the Conformational Dynamics of the Molecular Chaperone Hsp90
Rehn, A., Moroni, E., Zierer, B. K., Tippel, F., Morra, G., John, C., Richter, K., Colombo, G., & Büchner, J. (2016) · Journal of Molecular Biology · doi:10.1016/j.jmb.2016.09.014 · Cited by 64 · see citing works
Atomic view of the energy landscape in the allosteric regulation of Abl kinase
Saleh, T., Rossi, P., & Kalodimos, C. G. (2017) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.3470 · Cited by 65 · see citing works
van Zundert, G. C. P., Hudson, B. M., de Oliveira, S. H. P., Keedy, D. A., Fonseca, R., Héliou, A., Suresh, P., Borrelli, K. W., Day, T., Fraser, J. S., et al. (2018) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.8b01292 · Cited by 65 · see citing works
Experimental basis for a new allosteric model for multisubunit proteins
Viappiani, C., Abbruzzetti, S., Ronda, L., Bettati, S., Henry, E. R., Mozzarelli, A., & Eaton, W. A. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1413566111 · Cited by 64 · see citing works
Rangarajan, S., He, Y., Chen, Y.-H., Kerzic, M. C., Ma, B., Gowthaman, R., Pierce, B. G., Nussinov, R., Mariuzza, R. A., & Orban, J. P. (2018) · Journal of Biological Chemistry · doi:10.1074/jbc.ra118.003832 · Cited by 64 · see citing works
Neutral Peptides in the Gas Phase: Conformation and Aggregation Issues
Gloaguen, E., Mons, M., Schwing, K., & Gerhards, M. (2020) · Chemical Reviews · doi:10.1021/acs.chemrev.0c00168 · Cited by 63 · see citing works
Mazal, H., Iljina, M., Barak, Y., Elad, N., Rosenzweig, R., Goloubinoff, P., Riven, I., & Haran, G. (2019) · Nature Communications · doi:10.1038/s41467-019-09474-6 · Cited by 63 · see citing works
The genotype‐phenotype landscape of an allosteric protein
Tack, D. S., Tonner, P. D., Pressman, A., Olson, N. D., Levy, S. F., Romantseva, E. F., Alperovich, N., Vasilyeva, O. B., & Ross, D. (2021) · Molecular Systems Biology · doi:10.15252/msb.202010179 · Cited by 59 · see citing works
Intrinsic Conformational Plasticity of Native EmrE Provides a Pathway for Multidrug Resistance
Cho, M., Gayen, A., Banigan, J. R., Leninger, M., & Traaseth, N. J. (2014) · Journal of the American Chemical Society · doi:10.1021/ja503145x · Cited by 62 · see citing works
Cu(I)-mediated Allosteric Switching in a Copper-sensing Operon Repressor (CsoR)
Chang, F. J., Coyne, H. J., Cubillas, C. A., Vinuesa, P., Fang, X., Ma, Z., Ma, D., Helmann, J. D., Santos, A. G.-D. L., Wang, Y., et al. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.556704 · Cited by 62 · see citing works
Lys63-linked ubiquitin chain adopts multiple conformational states for specific target recognition
Liu, Z., Gong, Z., Jiang, W.-X., Yang, J., Zhu, W.-K., Guo, D.-C., Zhang, W.-P., Liu, M.-L., & Tang, C. (2015) · eLife · doi:10.7554/elife.05767 · Cited by 60 · see citing works
Lukman, S., Lane, D. P., & Verma, C. S. (2013) · PLoS ONE · doi:10.1371/journal.pone.0080221 · Cited by 60 · see citing works
Fluctuations within Folded Proteins: Implications for Thermodynamic and Allosteric Regulation
DuBay, K. H., Bowman, G. R., & Geissler, P. L. (2015) · Accounts of Chemical Research · doi:10.1021/ar500351b · Cited by 60 · see citing works
Enzymes at work are enzymes in motion
Saleh, T., & Kalodimos, C. G. (2017) · Science · doi:10.1126/science.aal4632 · Cited by 60 · see citing works
Sequence of Events in Measles Virus Replication: Role of Phosphoprotein-Nucleocapsid Interactions
Brunel, J., Chopy, D., Dosnon, M., Bloyet, L.-M., Devaux, P., Urzua, É., Cattaneo, R., Longhi, S., & Gerlier, D. (2014) · Journal of Virology · doi:10.1128/jvi.00664-14 · Cited by 59 · see citing works
Changes in conformational dynamics of basic side chains upon protein–DNA association
Esadze, A., Chen, C., Zandarashvili, L., Roy, S., Pettitt, B. M., & Iwahara, J. (2016) · Nucleic Acids Research · doi:10.1093/nar/gkw531 · Cited by 59 · see citing works
- Authors
- Tzeng, S.-R., & Kalodimos, C. G.
- Affiliations
- Rutgers, The State University of New Jersey (US)
- Corresponding author
- Kalodimos, Charalampos G.
- Venue
- Nature
- Published
- 2012-07-11
- Volume
- 488
- Issue
- 7410
- Pages
- 236-240
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2009239521
- Cited by
- 545
- References
- 30
- Citations by year
- 2026: 25 · 2025: 27 · 2024: 33 · 2023: 43 · 2022: 26 · 2021: 30 · 2020: 29 · 2019: 42 · 2018: 53 · 2017: 40 · 2016: 42 · 2015: 48 · 2014: 47 · 2013: 51 · 2012: 9
- FWCI
- 19.86
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- National Science Foundation
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Physical Sciences › Chemistry › Spectroscopy › Advanced NMR Techniques and Applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Diffusion and Search Dynamics
- Keywords
- CAP, protein-DNA interactions, conformational entropy, protein internal dynamics, protein conformational states, DNA-binding domain, protein structure-function relationship, protein variants, binding affinity, binding thermodynamics
- MeSH terms
- Binding Sites, Cyclic AMP Receptor Protein, DNA, Models, Molecular, Motion, Protein Binding, Time Factors, Protein Structure, Tertiary, Entropy, Nuclear Magnetic Resonance, Biomolecular
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