1DI8

THE STRUCTURE OF CYCLIN-DEPENDENT KINASE 2 (CDK2) IN COMPLEX WITH 4-[3-HYDROXYANILINO]-6,7-DIMETHOXYQUINAZOLINE

1DI8 の概要

• エントリーDOI: 10.2210/pdb1di8/pdb
• 関連するPDBエントリー: 1DI9
• 分子名称: CYCLIN-DEPENDENT KINASE 2, 4-[3-HYDROXYANILINO]-6,7-DIMETHOXYQUINAZOLINE (3 entities in total)
• 機能のキーワード: serine/threonine protein kinase, cell cycle, atp-binding, transferase
• 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: 34273.80

構造登録者

Shewchuk, L.,Hassell, A.,Kuyper, L.F. (登録日: 1999-11-29, 公開日: 2000-11-29, 最終更新日: 2024-02-07)

主引用文献

Shewchuk, L.,Hassell, A.,Wisely, B.,Rocque, W.,Holmes, W.,Veal, J.,Kuyper, L.F.
Binding mode of the 4-anilinoquinazoline class of protein kinase inhibitor: X-ray crystallographic studies of 4-anilinoquinazolines bound to cyclin-dependent kinase 2 and p38 kinase.
J.Med.Chem., 43:133-138, 2000

PubMed Abstract: 4-Anilinoquinazolines represent an important class of protein kinase inhibitor. Modes of binding for two members of this inhibitor class were determined by X-ray crystallographic analysis of one inhibitor (4-[3-hydroxyanilino]-6,7-dimethoxyquinazoline) in complex with cyclin-dependent kinase 2 (CDK2) and the other (4-[3-methylsulfanylanilino]-6,7-dimethoxyquinazoline) in complex with p38 kinase. In both inhibitor/kinase structures, the 4-anilinoquinazoline was bound in the ATP site with the quinazoline ring system oriented along the peptide strand that links the two domains of the protein and with the anilino substituent projecting into a hydrophobic pocket within the protein interior. In each case, the nitrogen at position-1 of the quinazoline accepted a hydrogen bond from a backbone NH (CDK2, Leu-83; p38, Met-109) of the domain connector strand, and aromatic hydrogen atoms at C2 and C8 interacted with backbone carbonyl oxygen atoms of the peptide strand. The anilino group of the CDK2-bound compound was essentially coplanar with the quinazoline ring system and occupied a pocket between Lys-33 and Phe-80. For the p38-bound inhibitor, the anilino group was angled out of plane and was positioned between Lys-53 and Thr-106 in a manner similar to that observed for the aryl substituent of the pyridinylimidazole class of inhibitor.

PubMed: 10633045
DOI: 10.1021/jm990401t

実験手法

X-RAY DIFFRACTION (2.2 Å)