1W0X

Crystal structure of human CDK2 in complex with the inhibitor olomoucine.

Summary for 1W0X

• Entry DOI: 10.2210/pdb1w0x/pdb
• Related: 1AQ1 1B38 1B39 1BUH 1CKP 1DI8 1DM2 1E1V 1E1X 1E9H 1F5Q 1FIN 1FQ1 1FVT 1FVV 1G5S 1GIH 1GII 1GIJ 1GY3 1GZ8 1H00 1H01 1H07 1H08 1H0V 1H0W 1H1P 1H1Q 1H1R 1H1S 1H24 1H25 1H26 1H27 1H28 1HCK 1HCL 1JST 1JSU 1JSV 1JVP 1KE5 1KE6 1KE7 1KE8 1KE9 1OGU 1OI9 1OIQ 1OIR 1OIT 1OIU 1OIY 1OKU 1OKV 1OKW 1OL1 1OL2 1P2A 1P5E 1PF8 1PKD 1PW2 1PXI 1PXJ 1PXK 1PXL 1PXM 1PXN 1PXO 1PXP 1QMZ 1R78 1URC 1URW 1V1K 1VYW 1VYZ
• Descriptor: CYCLIN-DEPENDENT KINASE 2, OLOMOUCINE (3 entities in total)
• Functional Keywords: protein kinase inhibitors, cyclin-dependent kinase, cell cycle regulation, cancer, transferase, serine/threonine -protein kinase, atp-binding
• Biological source: HOMO SAPIENS (HUMAN)
• Cellular location: Cytoplasm, cytoskeleton, microtubule organizing center, centrosome: P24941
• Total number of polymer chains: 1
• Total formula weight: 34274.83

Authors

Schulze-Gahmen, U.,Meijer, L.,Kim, S.-H. (deposition date: 2004-06-14, release date: 2005-01-14, Last modification date: 2024-05-08)

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-, 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 (2.2 Å)