ArticleNature chemical biology2010
Dynamics connect substrate recognition to catalysis in protein kinase A.
Article in Nature chemical biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 126 papers.
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Who cites it
126 citing papers in PubMed.
- Exploring the renoprotective potential of Beta vulgaris in diabetic nephropathy: an integrated network pharmacology, molecular docking and dynamics simulation study.Molecular diversity · 2026Article
- A PKA-selective inhibitor captures an open but more ordered conformation of the PKA catalytic subunit.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- The Power of Protein Dynamics in Binding and Allostery.Biochemistry · 2026Review
- Structural insights of AKT and its activation mechanism for drug development.Molecular diversity · 2025Review
- Protein Kinase A Phosphorylates a Conformationally High-energy State of Raf Kinase Inhibitory Protein.Journal of molecular biology · 2025Article
- Dynamic energy conversion in protein catalysis: From brownian motion to enzymatic function.Computational and structural biotechnology journal · 2025Review
- Nonallosteric activation of posttranslational modification enzymes by active site-directed inhibitors.Computational and structural biotechnology journal · 2024Article
- Tripartite interactions of PKA catalytic subunit and C-terminal domains of cardiac CaBMC biology · 2024Article
- Exploring the conformational landscape of protein kinases.Current opinion in structural biology · 2024Review
- Parsing Dynamics of Protein Backbone NH and Side-Chain Methyl Groups using Molecular Dynamics Simulations.Journal of chemical theory and computation · 2024Article
- Article
- Genetic Encoding of Phosphorylated Amino Acids into Proteins.Chemical reviews · 2024Review
- Perspectives on Computational Enzyme Modeling: From Mechanisms to Design and Drug Development.ACS omega · 2024Review
- Revealing eEF-2 kinase: recent structural insights into function.Trends in biochemical sciences · 2024Review
- Article
- An NMR portrait of functional and dysfunctional allosteric cooperativity in cAMP-dependent protein kinase A.FEBS letters · 2023Review
- Molecular-dynamics simulation methods for macromolecular crystallography.Acta crystallographica. Section D, Structural biology · 2023Article
- Binding and Functional Folding (BFF): A Physiological Framework for Studying Biomolecular Interactions and Allostery.Journal of molecular biology · 2022Review
- MptpA Kinetics Enhanced by Allosteric Control of an Active Conformation.Journal of molecular biology · 2022Article
- ATP-competitive inhibitors modulate the substrate binding cooperativity of a kinase by altering its conformational entropy.Science advances · 2022Article
66 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
7 authors.
Funding
Abstract
Atomic resolution studies of protein kinases have traditionally been carried out in the inhibitory state, limiting our current knowledge on the mechanisms of substrate recognition and catalysis. Using NMR, X-ray crystallography and thermodynamic measurements, we analyzed the substrate recognition process of cAMP-dependent protein kinase (PKA), finding that entropy and protein dynamics play a prominent role. The nucleotide acts as a dynamic and allosteric activator by coupling the two lobes of apo PKA, enhancing the enzyme dynamics synchronously and priming it for catalysis. The formation of the ternary complex is entropically driven, and NMR spin relaxation data reveal that both substrate and PKA are dynamic in the closed state. Our results show that the enzyme toggles between open and closed states, which indicates that a conformational selection rather than an induced-fit mechanism governs substrate recognition.
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