2ZMD

Crystal structure of human Mps1 catalytic domain T686A mutant in complex with SP600125 inhibitor

2ZMD の概要

• エントリーDOI: 10.2210/pdb2zmd/pdb
• 関連するPDBエントリー: 2ZMC
• 分子名称: Dual specificity protein kinase TTK, 2,6-DIHYDROANTHRA/1,9-CD/PYRAZOL-6-ONE, 2-(2-(2-(2-(2-(2-ETHOXYETHOXY)ETHOXY)ETHOXY)ETHOXY)ETHOXY)ETHANOL, ... (4 entities in total)
• 機能のキーワード: kinase, mps1, sp600125, t686a, atp-binding, nucleotide-binding, phosphoprotein, serine/threonine-protein kinase, transferase, tyrosine-protein kinase
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 44848.97

構造登録者

Chu, M.L.H.,Chavas, L.M.G.,Douglas, K.T.,Eyers, P.A.,Tabernero, L. (登録日: 2008-04-16, 公開日: 2008-05-13, 最終更新日: 2023-11-01)

主引用文献

Chu, M.L.,Chavas, L.M.,Douglas, K.T.,Eyers, P.A.,Tabernero, L.
Crystal structure of the catalytic domain of the mitotic checkpoint kinase Mps1 in complex with SP600125.
J.Biol.Chem., 283:21495-21500, 2008

PubMed Abstract: Chromosomal instability can result from defective control of checkpoints and is associated with malignant cell growth. Monopolar spindle 1 (Mps1) is a dual-specificity protein kinase that has important roles in the prevention of aneuploidy during the cell cycle and might therefore be a potential target for new therapeutic agents in the treatment of cancer. To gain insights into the molecular mechanism of Mps1 inhibition by small molecules, we determined the x-ray structure of Mps1, both alone and in complex with the ATP-competitive inhibitor SP600125. Mps1 adopts a classic protein kinase fold, with the inhibitor sitting in the ATP-binding site where it is stabilized by hydrophobic interactions. We identified a secondary pocket, not utilized by SP600125, which might be exploited for the rational design of specific Mps1 inhibitors. These structures provide important insights into the interaction of this protein kinase with small molecules and suggest potential mechanisms for Mps1 regulation.

PubMed: 18480048
DOI: 10.1074/jbc.M803026200

実験手法

X-RAY DIFFRACTION (2.88 Å)