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Allosteric cooperativity in protein kinase A.

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.

SUBMITTER: Masterson LR

PROVIDER: S-EPMC2206566 | biostudies-literature | 2008 Jan

REPOSITORIES: biostudies-literature

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Allosteric cooperativity in protein kinase A.

Masterson Larry R LR Mascioni Alessandro A Traaseth Nathaniel J NJ Taylor Susan S SS Veglia Gianluigi G

Proceedings of the National Academy of Sciences of the United States of America 20080104 2

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 ...[more]

PMID: 18178622

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