2EXM

Human CDK2 in complex with isopentenyladenine

Summary for 2EXM

• Entry DOI: 10.2210/pdb2exm/pdb
• Descriptor: Cell division protein kinase 2, N-(3-METHYLBUT-2-EN-1-YL)-9H-PURIN-6-AMINE (3 entities in total)
• Functional Keywords: typical protein kinase fold, ligand binding pocket between n-terminal and c-terminal domain, transferase
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm, cytoskeleton, microtubule organizing center, centrosome: P24941
• Total number of polymer chains: 1
• Total formula weight: 34179.73

Authors

Schulze-Gahmen, U. (deposition date: 2005-11-08, release date: 2005-12-27, Last modification date: 2024-02-14)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.8 Å)