2H9V

Structural basis for induced-fit binding of Rho-kinase to the inhibitor Y27632

2H9V の概要

• エントリーDOI: 10.2210/pdb2h9v/pdb
• 関連するPDBエントリー: 2F2U
• 分子名称: Rho-associated protein kinase 2, (R)-TRANS-4-(1-AMINOETHYL)-N-(4-PYRIDYL) CYCLOHEXANECARBOXAMIDE (3 entities in total)
• 機能のキーワード: protein kinase-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: 1
• 化学式量合計: 46023.36

構造登録者

Yamaguchi, H.,Miwa, Y.,Kasa, M.,Kitano, K.,Amano, M.,Kaibuchi, K.,Hakoshima, T. (登録日: 2006-06-12, 公開日: 2006-12-05, 最終更新日: 2024-03-13)

主引用文献

Yamaguchi, H.,Miwa, Y.,Kasa, M.,Kitano, K.,Amano, M.,Kaibuchi, K.,Hakoshima, T.
Structural basis for induced-fit binding of Rho-kinase to the inhibitor Y-27632
J.Biochem.(Tokyo), 140:305-311, 2006

PubMed Abstract: Rho-kinase is a main player in the regulation of cytoskeletal events and a promising drug target in the treatment of both vascular and neurological disorders. Here we report the crystal structure of the Rho-kinase catalytic domain in complex with the specific inhibitor Y-27632. Comparison with the structure of PKA bound to this inhibitor revealed a potential induced-fit binding mode that can be accommodated by the phosphate binding loop. This binding mode resembles to that observed in the Rho-kinase-fasudil complex. A structural database search indicated that a pocket underneath the phosphate-binding loop is present that favors binding to a small aromatic ring. Introduction of such a ring group might spawn a new modification scheme of pre-existing protein kinase inhibitors for improved binding capability.

PubMed: 16891330
DOI: 10.1093/jb/mvj172

実験手法

X-RAY DIFFRACTION (3.1 Å)