Allosteric cooperativity in protein kinase A.
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Masterson LR, Mascioni A, Traaseth NJ, Taylor SS, Veglia G
Allosteric cooperativity in protein kinase A.
Proc Natl Acad Sci U S A. 2008 Jan 15;105(2):506-11. doi: 10.1073/pnas.0709214104. Epub 2008 Jan 4.
- PubMed ID
- 18178622 [ View in PubMed]
- 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.