Allosteric cooperativity in protein kinase A
- 15 January 2008
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 105 (2), 506-511
- https://doi.org/10.1073/pnas.0709214104
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.This publication has 56 references indexed in Scilit:
- A solution NMR study showing that active site ligands and nucleotides directly perturb the allosteric equilibrium in aspartate transcarbamoylaseProceedings of the National Academy of Sciences of the United States of America, 2007
- Signal transduction pathway of TonB-dependent transportersProceedings of the National Academy of Sciences of the United States of America, 2007
- cAMP activation of PKA defines an ancient signaling mechanismProceedings of the National Academy of Sciences of the United States of America, 2007
- Surface comparison of active and inactive protein kinases identifies a conserved activation mechanismProceedings of the National Academy of Sciences of the United States of America, 2006
- Dynamically driven protein allosteryNature Structural & Molecular Biology, 2006
- Dynamic Coupling and Allosteric Behavior in a Nonallosteric ProteinBiochemistry, 2006
- Solution Scattering Reveals Large Differences in the Global Structures of Type II Protein Kinase A IsoformsJournal of Molecular Biology, 2006
- Intrinsic dynamics of an enzyme underlies catalysisNature, 2005
- Folding and binding cascades: Dynamic landscapes and population shiftsProtein Science, 2000
- NMRPipe: A multidimensional spectral processing system based on UNIX pipesJournal of Biomolecular NMR, 1995