1NVR

The Complex Structure Of Checkpoint Kinase Chk1/Staurosporine

1NVR の概要

• エントリーDOI: 10.2210/pdb1nvr/pdb
• 関連するPDBエントリー: 1nvq
• 分子名称: Serine/threonine-protein kinase Chk1, Peptide ASVSA, SULFATE ION, ... (5 entities in total)
• 機能のキーワード: chk1-staurosporine complex, transferase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Nucleus: O14757
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 34039.04

構造登録者

Zhao, B.,Bower, M.J.,McDevitt, P.J.,Zhao, H.,Davis, S.T.,Johanson, K.O.,Green, S.M.,Concha, N.O.,Zhou, B.B. (登録日: 2003-02-04, 公開日: 2003-04-08, 最終更新日: 2023-08-16)

主引用文献

Zhao, B.,Bower, M.J.,McDevitt, P.J.,Zhao, H.,Davis, S.T.,Johanson, K.O.,Green, S.M.,Concha, N.O.,Zhou, B.B.
Structural Basis for Chk1 Inhibition by UCN-01
J.Biol.Chem., 277:46609-46615, 2002

PubMed Abstract: Chk1 is a serine-threonine kinase that plays an important role in the DNA damage response, including G(2)/M cell cycle control. UCN-01 (7-hydroxystaurosporine), currently in clinical trials, has recently been shown to be a potent Chk1 inhibitor that abrogates the G(2)/M checkpoint induced by DNA-damaging agents. To understand the structural basis of Chk1 inhibition by UCN-01, we determined the crystal structure of the Chk1 kinase domain in complex with UCN-01. Chk1 structures with staurosporine and its analog SB-218078 were also determined. All three compounds bind in the ATP-binding pocket of Chk1, producing only slight changes in the protein conformation. Selectivity of UCN-01 toward Chk1 over cyclin-dependent kinases can be explained by the presence of a hydroxyl group in the lactam moiety interacting with the ATP-binding pocket. Hydrophobic interactions and hydrogen-bonding interactions were observed in the structures between UCN-01 and the Chk1 kinase domain. The high structural complementarity of these interactions is consistent with the potency and selectivity of UCN-01.

PubMed: 12244092
DOI: 10.1074/jbc.M201233200

実験手法

X-RAY DIFFRACTION (1.8 Å)