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2F2U

crystal structure of the Rho-kinase kinase domain

Summary for 2F2U
Entry DOI10.2210/pdb2f2u/pdb
DescriptorRho-associated protein kinase 2, 5-(1,4-DIAZEPAN-1-SULFONYL)ISOQUINOLINE (3 entities in total)
Functional Keywordsenzyme-inhibitor complex, transferase
Biological sourceBos taurus (cattle)
Cellular locationCytoplasm: Q28021
Total number of polymer chains2
Total formula weight92134.78
Authors
Yamaguchi, H.,Hakoshima, T. (deposition date: 2005-11-18, release date: 2006-04-25, Last modification date: 2023-10-25)
Primary citationYamaguchi, H.,Kasa, M.,Amano, M.,Kaibuchi, K.,Hakoshima, T.
Molecular mechanism for the regulation of rho-kinase by dimerization and its inhibition by fasudil
Structure, 14:589-600, 2006
Cited by
PubMed Abstract: 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.
PubMed: 16531242
DOI: 10.1016/j.str.2005.11.024
PDB entries with the same primary citation
Experimental method
X-RAY DIFFRACTION (2.4 Å)
Structure validation

238582

數據於2025-07-09公開中

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