ArticleBiochemistry2012
Conformational equilibrium of N-myristoylated cAMP-dependent protein kinase A by molecular dynamics simulations.
Article in Biochemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 32 citations in OpenAlex.
- In silico study to identify novel NEK7 inhibitors from natural sources by a combination strategy.Molecular diversity · 2025Article
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- TYROSINE KINASES: COMPLEX MOLECULAR SYSTEMS CHALLENGING COMPUTATIONAL METHODOLOGIES.The European physical journal. B · 2021Article
- Is Disrupted Nucleotide-Substrate Cooperativity a Common Trait for Cushing's Syndrome Driving Mutations of Protein Kinase A?Journal of molecular biology · 2021Article
- A tripartite cooperative mechanism confers resistance of the protein kinase A catalytic subunit to dephosphorylation.The Journal of biological chemistry · 2020Article
- Conformational Landscape of the PRKACA-DNAJB1 Chimeric Kinase, the Driver for Fibrolamellar Hepatocellular Carcinoma.Scientific reports · 2018Article
- The Molecular Basis for Specificity at the Level of the Protein Kinase a Catalytic Subunit.Frontiers in endocrinology · 2018Review
- Cleavage Alters the Molecular Determinants of Protein Kinase C-δ Catalytic Activity.Molecular and cellular biology · 2017Article
- Binding mechanism and dynamic conformational change of C subunit of PKA with different pathways.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- A dynamic hydrophobic core orchestrates allostery in protein kinases.Science advances · 2017Article
- Article
- Solution NMR Spectroscopy for the Study of Enzyme Allostery.Chemical reviews · 2016Review
- Role of Dynamics in the Autoinhibition and Activation of the Hyperpolarization-activated Cyclic Nucleotide-modulated (HCN) Ion Channels.The Journal of biological chemistry · 2015Article
- Mapping the Hydrogen Bond Networks in the Catalytic Subunit of Protein Kinase A Using H/D Fractionation Factors.Biochemistry · 2015Article
- A tool set to map allosteric networks through the NMR chemical shift covariance analysis.Scientific reports · 2014Article
- NMR mapping of protein conformational landscapes using coordinated behavior of chemical shifts upon ligand binding.Physical chemistry chemical physics : PCCP · 2014Article
- Article
- Influence of N-myristylation and ligand binding on the flexibility of the catalytic subunit of protein kinase A.Biochemistry · 2013Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
The catalytic subunit of protein kinase A (PKA-C) is subject to several post- or cotranslational modifications that regulate its activity both spatially and temporally. Among those, N-myristoylation increases the kinase affinity for membranes and might also be implicated in substrate recognition and allosteric regulation. Here, we investigated the effects of N-myristoylation on the structure, dynamics, and conformational equilibrium of PKA-C using atomistic molecular dynamics simulations. We found that the myristoyl group inserts into the hydrophobic pocket and leads to a tighter packing of the A-helix against the core of the enzyme. As a result, the conformational dynamics of the A-helix are reduced and its motions are more coupled with the active site. Our simulations suggest that cation-π interactions among W30, R190, and R93 are responsible for coupling these motions. Two major conformations of the myristoylated N-terminus are the most populated: a long loop (LL conformation), similar to Protein Data Bank (PDB) entry 1CMK , and a helix-turn-helix structure (HTH conformation), similar to PDB entry 4DFX , which shows stronger coupling between the conformational dynamics observed at the A-helix and active site. The HTH conformation is stabilized by S10 phosphorylation of the kinase via ionic interactions between the protonated amine of K7 and the phosphate group on S10, further enhancing the dynamic coupling to the active site. These results support a role of N-myristoylation in the allosteric regulation of PKA-C.
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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.