Allosteric cooperativity in protein kinase A
Year: 2008
Type: article
Abstract: Allosteric signaling in proteins requires long-range communication mediated by highly conserved residues, often triggered by ligand binding. In this article, we map the allosteric network in the catalytic subunit of protein kinase A using NMR spectroscopy. We show that positive allosteric cooperativity is generated by nucleotide and substrate binding during the transitions through the major conformational states: apo, intermediate, and closed. The allosteric network is disrupted by a single site mutation (Y204A), which also decouples the cooperativity of ligand binding. Because protein kinase A is the prototype for the entire kinome, these findings may serve as a paradigm for describing long-range coupling in other protein kinases.
Institutions: University of California San Diego, University of Minnesota
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Awards: G1226503214, G1822506642, WIDE-BORE 9.4 TESLA NMR SPECTROMETER FOR UW-MADISON, G361034356, PROTEIN KINASE: PRIMARY STRUCTURE AND CAMP INTERACTION, Structural Basis Of Dilated Cardiomyopathy, National Biomedical NMR Resource at Madison, Structural Basis of Heart Muscle Function and Disease, CONSOLE UPGRADES FOR NMR FACILITY, G6336637667, Protein Kinase - Primary Structure and cAMP Interaction, NMR Structural Analysis of Calcium Regulation in Muscle, Chemistry-Biology Interface Training Grant, 900 MHz NMR Spectrometer Biomolecular Investigations
OpenAlex ID: W2156232082