2F2U

crystal structure of the Rho-kinase kinase domain

2F2U の概要

• エントリーDOI: 10.2210/pdb2f2u/pdb
• 分子名称: Rho-associated protein kinase 2, 5-(1,4-DIAZEPAN-1-SULFONYL)ISOQUINOLINE (3 entities in total)
• 機能のキーワード: enzyme-inhibitor complex, transferase
• 由来する生物種: Bos taurus (cattle)
• 細胞内の位置: Cytoplasm: Q28021
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 92134.78

構造登録者

Yamaguchi, H.,Hakoshima, T. (登録日: 2005-11-18, 公開日: 2006-04-25, 最終更新日: 2023-10-25)

主引用文献

Yamaguchi, 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

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

実験手法

X-RAY DIFFRACTION (2.4 Å)