2exm
Human CDK2 in complex with isopentenyladenine
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OverviewOverview
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.
About this StructureAbout this Structure
2EXM is a Single protein structure of sequence from Homo sapiens with ZIP as ligand. Active as Non-specific serine/threonine protein kinase, with EC number 2.7.11.1 Full crystallographic information is available from OCA.
ReferenceReference
Multiple modes of ligand recognition: crystal structures of cyclin-dependent protein kinase 2 in complex with ATP and two inhibitors, olomoucine and isopentenyladenine., Schulze-Gahmen U, Brandsen J, Jones HD, Morgan DO, Meijer L, Vesely J, Kim SH, Proteins. 1995 Aug;22(4):378-91. PMID:7479711
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