ArticleStructure (London, England : 1993)2014
Synchronous opening and closing motions are essential for cAMP-dependent protein kinase A signaling.
Article in Structure (London, England : 1993), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 64 citations in OpenAlex.
- Article
- 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
- Allosteric binding cooperativity in kinases signaling, signalopathies, and drug development.Current opinion in structural biology · 2025Review
- Article
- ATP-competitive inhibitors modulate the substrate binding cooperativity of a kinase by altering its conformational entropy.Science advances · 2022Article
- Joint neutron/molecular dynamics vibrational spectroscopy reveals softening of HIV-1 protease upon binding of a tight inhibitor.Physical chemistry chemical physics : PCCP · 2022Article
- Defective internal allosteric network imparts dysfunctional ATP/substrate-binding cooperativity in oncogenic chimera of protein kinase A.Communications biology · 2021Article
- Allosteric Pathways Originating at Cysteine Residues in Regulators of G-Protein Signaling Proteins.Biophysical journal · 2021Article
- NMR and computational methods for molecular resolution of allosteric pathways in enzyme complexes.Biophysical reviews · 2020Review
- Protein kinase A in the neutron beam: Insights for catalysis from directly observing protons.Methods in enzymology · 2020Article
- A Dynamic Switch in Inactive p38γ Leads to an Excited State on the Pathway to an Active Kinase.Biochemistry · 2019Article
- A Conserved Allosteric Pathway in Tyrosine Kinase Regulation.Structure (London, England : 1993) · 2019Article
- Dynamic allostery-based molecular workings of kinase:peptide complexes.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Review
- Globally correlated conformational entropy underlies positive and negative cooperativity in a kinase's enzymatic cycle.Nature communications · 2019Article
- Probing Protein-Protein Interactions Using Asymmetric Labeling and Carbonyl-Carbon Selective Heteronuclear NMR Spectroscopy.Molecules (Basel, Switzerland) · 2018Review
- PKA-RII subunit phosphorylation precedes activation by cAMP and regulates activity termination.The Journal of cell biology · 2018Article
- Conformational Landscape of the PRKACA-DNAJB1 Chimeric Kinase, the Driver for Fibrolamellar Hepatocellular Carcinoma.Scientific reports · 2018Article
- Cleavage Alters the Molecular Determinants of Protein Kinase C-δ Catalytic Activity.Molecular and cellular biology · 2017Article
- Gorge Motions of Acetylcholinesterase Revealed by Microsecond Molecular Dynamics Simulations.Scientific reports · 2017Article
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Conformational fluctuations play a central role in enzymatic catalysis. However, it is not clear how the rates and the coordination of the motions affect the different catalytic steps. Here, we used NMR spectroscopy to analyze the conformational fluctuations of the catalytic subunit of the cAMP-dependent protein kinase (PKA-C), a ubiquitous enzyme involved in a myriad of cell signaling events. We found that the wild-type enzyme undergoes synchronous motions involving several structural elements located in the small lobe of the kinase, which is responsible for nucleotide binding and release. In contrast, a mutation (Y204A) located far from the active site desynchronizes the opening and closing of the active cleft without changing the enzyme's structure, rendering it catalytically inefficient. Since the opening and closing motions govern the rate-determining product release, we conclude that optimal and coherent conformational fluctuations are necessary for efficient turnover of protein kinases.
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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.