2f2u
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(New page: 200px<br /><applet load="2f2u" size="450" color="white" frame="true" align="right" spinBox="true" caption="2f2u, resolution 2.400Å" /> '''crystal structure o...)
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Revision as of 08:12, 21 November 2007
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crystal structure of the Rho-kinase kinase domain
Overview
Rho-kinase is a key regulator of cytoskeletal events and a promising drug, target in the treatment of vascular diseases and neurological disorders., Unlike other protein kinases, Rho-kinase requires both N- and C-terminal, extension segments outside the kinase domain for activity, although the, details of this requirement have been elusive. The crystal structure of an, active Rho-kinase fragment containing the kinase domain and both the, extensions revealed a head-to-head homodimer through the N-terminal, extension forming a helix bundle that structurally integrates the, C-terminal extension. This structural organization enables binding of the, C-terminal hydrophobic motif to the N-terminal lobe, which defines the, correct disposition of helix alphaC that is important for the catalytic, activity. The bound inhibitor fasudil significantly alters the, conformation and, consequently, the mode of interaction with the catalytic, cleft that contains local structural changes. Thus, both kinase and drug, conformational pliability and stability confer selectivity.
About this Structure
2F2U is a Single protein structure of sequence from Bos taurus with M77 as ligand. Active as Non-specific serine/threonine protein kinase, with EC number 2.7.11.1 Full crystallographic information is available from OCA.
Reference
Molecular mechanism for the regulation of rho-kinase by dimerization and its inhibition by fasudil., Yamaguchi H, Kasa M, Amano M, Kaibuchi K, Hakoshima T, Structure. 2006 Mar;14(3):589-600. PMID:16531242
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