ArticleThe Journal of biological chemistry2015
The Role of Protein-Ligand Contacts in Allosteric Regulation of the Escherichia coli Catabolite Activator Protein.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 40 citations in OpenAlex.
- A Structure-Based Analysis of the Evolution of Transcription Factors of the FNR/CRP Family.Biomolecules · 2026Review
- Neuromodulators as Interdomain Signaling Molecules Capable of Occupying Effector Binding Sites in Bacterial Transcription Factors.International journal of molecular sciences · 2023Article
- Structural basis for the inhibitory mechanism of auranofin and gold(I) analogues againstComputational and structural biotechnology journal · 2023Article
- Allosteric rescue of catalytically impaired ATP phosphoribosyltransferase variants links protein dynamics to active-site electrostatic preorganisation.Nature communications · 2022Article
- Drug design by machine-trained elastic networks: predicting Ser/Thr-protein kinase inhibitors' activities.Molecular diversity · 2021Article
- Substitutions at Nonconserved Rheostat Positions Modulate Function by Rewiring Long-Range, Dynamic Interactions.Molecular biology and evolution · 2021Article
- Computational analysis of dynamic allostery and control in the SARS-CoV-2 main protease.Journal of the Royal Society, Interface · 2021Article
- Article
- Nucleotide Second Messenger-Based Signaling in Extreme Acidophiles of theFrontiers in microbiology · 2019Article
- Interplay of self-association and conformational flexibility in regulating protein function.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2018Review
- Signalling networks and dynamics of allosteric transitions in bacterial chaperonin GroEL: implications for iterative annealing of misfolded proteins.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2018Review
- Reversing allosteric communication: From detecting allosteric sites to inducing and tuning targeted allosteric response.PLoS computational biology · 2018Article
- The intracellular immune receptor Rx1 regulates the DNA-binding activity of a Golden2-like transcription factor.The Journal of biological chemistry · 2018Article
- Energetic redistribution in allostery to execute protein function.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Dynamic Transmission of Protein Allostery without Structural Change: Spatial Pathways or Global Modes?Biophysical journal · 2015Article
- Small Molecule Targeting of Protein-Protein Interactions through Allosteric Modulation of Dynamics.Molecules (Basel, Switzerland) · 2015Review
- cAMP is an allosteric modulator of DNA-binding specificity in the cAMP receptor protein from Mycobacterium tuberculosis.The Journal of biological chemistryArticle
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Allostery is a fundamental process by which ligand binding to a protein alters its activity at a distant site. Both experimental and theoretical evidence demonstrate that allostery can be communicated through altered slow relaxation protein dynamics without conformational change. The catabolite activator protein (CAP) of Escherichia coli is an exemplar for the analysis of such entropically driven allostery. Negative allostery in CAP occurs between identical cAMP binding sites. Changes to the cAMP-binding pocket can therefore impact the allosteric properties of CAP. Here we demonstrate, through a combination of coarse-grained modeling, isothermal calorimetry, and structural analysis, that decreasing the affinity of CAP for cAMP enhances negative cooperativity through an entropic penalty for ligand binding. The use of variant cAMP ligands indicates the data are not explained by structural heterogeneity between protein mutants. We observe computationally that altered interaction strength between CAP and cAMP variously modifies the change in allosteric cooperativity due to second site CAP mutations. As the degree of correlated motion between the cAMP-contacting site and a second site on CAP increases, there is a tendency for computed double mutations at these sites to drive CAP toward noncooperativity. Naturally occurring pairs of covarying residues in CAP do not display this tendency, suggesting a selection pressure to fine tune allostery on changes to the CAP ligand-binding pocket without a drive to a noncooperative state. In general, we hypothesize an evolutionary selection pressure to retain slow relaxation dynamics-induced allostery in proteins in which evolution of the ligand-binding site is occurring.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.