2f2u
From Proteopedia
(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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| - | [[Image:2f2u.gif|left|200px]]<br /><applet load="2f2u" size=" | + | [[Image:2f2u.gif|left|200px]]<br /><applet load="2f2u" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="2f2u, resolution 2.400Å" /> | caption="2f2u, resolution 2.400Å" /> | ||
'''crystal structure of the Rho-kinase kinase domain'''<br /> | '''crystal structure of the Rho-kinase kinase domain'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Rho-kinase is a key regulator of cytoskeletal events and a promising drug | + | 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== | ==About this Structure== | ||
| - | 2F2U is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus] with M77 as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] Full crystallographic information is available from [http:// | + | 2F2U is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus] with <scene name='pdbligand=M77:'>M77</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2F2U OCA]. |
==Reference== | ==Reference== | ||
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[[Category: enzyme-inhibitor complex]] | [[Category: enzyme-inhibitor complex]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:17:13 2008'' |
Revision as of 15:17, 21 February 2008
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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 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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