title: Role of conformational entropy in the activity and regulation of the catalytic subunit of protein kinase A.
abstract: Protein kinase A (PKA) is the archetypical phosphokinase, sharing a catalytic core with the entire protein kinase superfamily. In eukaryotes, the ubiquitous location of PKA makes it one of the most important cellular signaling molecules, involved in a myriad of events. The catalytic subunit of PKA (PKA-C) is one of the most studied enzymes and was the first kinase to be crystallized; however, the effects of ligand binding, post-translational modifications and mutations on the activity of the kinase have been difficult to understand with only structural data. Here, we review our latest NMR studies on PKA-C, the results of which underscore the role of fast and slow conformational dynamics in the activation and inhibition of the kinase.
authors.affiliation: Department of Biochemistry, Biophysics & Molecular Biology, University of Minnesota, Jackson Hall, MN, USA; Department of Chemistry, University of Minnesota, Smith Hall, MN, USA.
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Veglia
authors.forename: Alessandro
authors.initials: A
authors.lastname: Cembran
mesh_terms: D000494:Allosteric Regulation; D020134:Catalytic Domain; D054751:Cyclic AMP-Dependent Protein Kinase Catalytic Subunits / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D019277:Entropy; D006801:Humans; D007700:Kinetics; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D011487:Protein Conformation
chemical_list: D054751:Cyclic AMP-Dependent Protein Kinase Catalytic Subunits
keywords: NMR relaxation; allostery; catalysis; conformational entropy; conformational selection; phospholamban; phosphorylation; protein kinase A; structural dynamics; substrate recognition
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