期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 105, 期 2, 页码 506-511出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0709214104
关键词
allostery; NMR; signaling; enzymes; chemical shift mapping
资金
- NCRR NIH HHS [S10 RR008438, P41 RR002301, S10 RR002781, P41RR02301] Funding Source: Medline
- NHLBI NIH HHS [K02 HL080081, HL080081, K02 HL080081-03] Funding Source: Medline
- NIGMS NIH HHS [GM64742, R01 GM072701-02, GM08700, R01 GM019301, P41 GM066326, R37 GM019301, R01 GM064742, P41GM66326, R01 GM072701, GM19301, R01 GM064742-02, T32 GM008700] Funding Source: Medline
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.
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