2EXM

Human CDK2 in complex with isopentenyladenine

2EXM の概要

• エントリーDOI: 10.2210/pdb2exm/pdb
• 分子名称: Cell division protein kinase 2, N-(3-METHYLBUT-2-EN-1-YL)-9H-PURIN-6-AMINE (3 entities in total)
• 機能のキーワード: typical protein kinase fold, ligand binding pocket between n-terminal and c-terminal domain, transferase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm, cytoskeleton, microtubule organizing center, centrosome: P24941
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 34179.73

構造登録者

Schulze-Gahmen, U. (登録日: 2005-11-08, 公開日: 2005-12-27, 最終更新日: 2024-02-14)

主引用文献

Schulze-Gahmen, U.,Brandsen, J.,Jones, H.D.,Morgan, D.O.,Meijer, L.,Vesely, J.,Kim, S.H.
Multiple modes of ligand recognition: crystal structures of cyclin-dependent protein kinase 2 in complex with ATP and two inhibitors, olomoucine and isopentenyladenine.
Proteins, 22:378-391, 1995

PubMed Abstract: Cyclin-dependent kinases (CDKs) are conserved regulators of the eukaryotic cell cycle with different isoforms controlling specific phases of the cell cycle. Mitogenic or growth inhibitory signals are mediated, respectively, by activation or inhibition of CDKs which phosphorylate proteins associated with the cell cycle. The central role of CDKs in cell cycle regulation makes them a potential new target for inhibitory molecules with anti-proliferative and/or anti-neoplastic effects. We describe the crystal structures of the complexes of CDK2 with a weakly specific CDK inhibitor, N6-(delta 2-isopentenyl)adenine, and a strongly specific inhibitor, olomoucine. Both inhibitors are adenine derivatives and bind in the adenine binding pocket of CDK2, but in an unexpected and different orientation from the adenine of the authentic ligand ATP. The N6-benzyl substituent in olomoucine binds outside the conserved binding pocket and is most likely responsible for its specificity. The structural information from the CDK2-olomoucine complex will be useful in directing the search for the next generation inhibitors with improved properties.

PubMed: 7479711
DOI: 10.1002/prot.340220408

実験手法

X-RAY DIFFRACTION (1.8 Å)