4Y8D

Crystal structure of Cyclin-G associated kinase (GAK) complexed with selective 12i inhibitor

4Y8D の概要

• エントリーDOI: 10.2210/pdb4y8d/pdb
• 分子名称: Cyclin-G-associated kinase, nanobody, 2-methoxy-4-[3-(morpholin-4-yl)[1,2]thiazolo[4,3-b]pyridin-6-yl]aniline, ... (5 entities in total)
• 機能のキーワード: transferase, kinase, nanobody, inhibitor, structural genomics, structural genomics consortium, sgc
• 由来する生物種: Homo sapiens (Human); 詳細
• 細胞内の位置: Cytoplasm, perinuclear region : O14976
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 107533.29

構造登録者

Chaikuad, A.,Heroven, C.,Nowak, R.,De Jonghe, S.,von Delft, F.,Arrowsmith, C.H.,Edwards, A.M.,Bountra, C.,Knapp, S.,Structural Genomics Consortium (SGC) (登録日: 2015-02-16, 公開日: 2015-04-08, 最終更新日: 2024-10-09)

主引用文献

Kovackova, S.,Chang, L.,Bekerman, E.,Neveu, G.,Barouch-Bentov, R.,Chaikuad, A.,Heroven, C.,Sala, M.,De Jonghe, S.,Knapp, S.,Einav, S.,Herdewijn, P.
Selective Inhibitors of Cyclin G Associated Kinase (GAK) as Anti-Hepatitis C Agents.
J.Med.Chem., 58:3393-3410, 2015

PubMed Abstract: Cyclin G associated kinase (GAK) emerged as a promising drug target for the treatment of viral infections. However, no potent and selective GAK inhibitors have been reported in the literature to date. This paper describes the discovery of isothiazolo[5,4-b]pyridines as selective GAK inhibitors, with the most potent congeners displaying low nanomolar binding affinity for GAK. Cocrystallization experiments revealed that these compounds behaved as classic type I ATP-competitive kinase inhibitors. In addition, we have demonstrated that these compounds exhibit a potent activity against hepatitis C virus (HCV) by inhibiting two temporally distinct steps in the HCV life cycle (i.e., viral entry and assembly). Hence, these GAK inhibitors represent chemical probes to study GAK function in different disease areas where GAK has been implicated (including viral infection, cancer, and Parkinson's disease).

PubMed: 25822739
DOI: 10.1021/jm501759m

実験手法

X-RAY DIFFRACTION (2.1 Å)