1995/08/01 by Ursula Schulze‐Gahmen, Jeroen Brandsen, Heather D. Jones +5 · 1 citation
Biochemistry, Genetics and Molecular Biology · Medicine · #Cancer, Hypoxia, and Metabolism #Cancer-related Molecular Pathways #Microtubule and mitosis dynamics
paper · doi:10.1002/prot.340220408
openalex publication_date 1995/08/01 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/28
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.