Structural basis for induced-fit binding of Rho-kinase to the inhibitor Y-27632

Hiroto Yamaguchi, Yukiko Miwa, Miyuki Kasa, Ken Kitano, Mutsuki Amano, Kozo Kaibuchi, Toshio Hakoshima

Research output: Contribution to journalArticlepeer-review

50 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)305-311
Number of pages7
JournalJournal of Biochemistry
Issue number3
Publication statusPublished - 09-2006
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology


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