1yhv
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(New page: 200px<br /> <applet load="1yhv" size="450" color="white" frame="true" align="right" spinBox="true" caption="1yhv, resolution 1.80Å" /> '''Crystal Structure o...)
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Revision as of 18:13, 12 November 2007
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Crystal Structure of PAK1 kinase domain with two point mutations (K299R, T423E)
Overview
The p21-activated kinases (PAKs) participate in cytoskeletal control, networks, downstream of Rho-family GTPases. A structure of PAK1 in an, autoregulated, "off" state showed that a regulatory region, N-terminal to, the kinase domain, forces the latter into an inactive conformation, prevents phosphorylation of Thr423 in the activation loop, and promotes, dimerization. We have now determined structures at 1.8 A resolution for, the free PAK1 kinase domain, with a mutation in the active site that, blocks enzymatic activity, and for the same domain with a "phosphomimetic", mutation in the activation loop. The two very similar structures show that, even in the absence of a phosphorylated Thr423, the kinase has an, essentially active conformation. When Cdc42 binds the regulatory region, and dissociates the dimer, PAK1 will be in an "intermediate-active" state, with a capacity to phosphorylate itself or other substrates even prior to, modification of its activation loop.
About this Structure
1YHV is a Single protein structure of sequence from Homo sapiens. Active as Non-specific serine/threonine protein kinase, with EC number 2.7.11.1 Full crystallographic information is available from OCA.
Reference
The active conformation of the PAK1 kinase domain., Lei M, Robinson MA, Harrison SC, Structure. 2005 May;13(5):769-78. PMID:15893667
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