The DOI matches its Crossref record; 30 of the 30 references it cites were found in a registry or an index.
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…
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“suggest that the observed changes in protein conformations and dynamics may alter protein activity [61].”
Citations
Cites
Dynamic personalities of proteins
Henzler-Wildman, K., & Kern, D. (2007) · Nature · doi:10.1038/nature06522 · Cited by 2,545
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
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 665
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
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
Binding of Small-Molecule Ligands to Proteins: “What You See” Is Not Always “What You Get”
Mobley, D. L., & Dill, K. A. (2009) · Structure · doi:10.1016/j.str.2009.02.010 · Cited by 598
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
Ishima, R., & Torchia, D. A. (2000) · Nature Structural Biology · doi:10.1038/78963 · Cited by 530
Yang, D., & Kay, L. E. (1996) · Journal of Molecular Biology · doi:10.1006/jmbi.1996.0581 · Cited by 459
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 436
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
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
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 434
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
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 294
Metadata
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
