2a0c

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spinqualitylabelsall models 2a0c, resolution 1.95Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

Human CDK2 in complex with olomoucine II, a novel 2,6,9-trisubstituted purine cyclin-dependent kinase inhibitor

Overview

The study describes the protein kinase selectivity profile, as well as the, binding mode of olomoucine II in the catalytic cleft of CDK2, as, determined from cocrystal analysis. Apart from the main cell, cycle-regulating kinase CDK2, olomoucine II exerts specificity for CDK7, and CDK9, with important functions in the regulation of RNA transcription., In vitro anticancer activity of the inhibitor in a panel of tumor cell, lines shows a wide potency range with a slight preference for cells, harboring a wild-type p53 gene. Cell-based assays confirmed activation of, p53 protein levels and events leading to accumulation of p21(WAF1)., Additionally, in olomoucine II-treated cells, Mdm2 was found to form a, complex with the ribosomal protein L11, which inhibits Mdm2 ubiquitin, ligase function. We conclude that perturbations in RNA synthesis may lead, to activation of p53 and that this contributes to the antiproliferative, potency of cyclindependent kinase inhibitors.

About this Structure

2A0C is a Single protein structure of sequence from Homo sapiens with CK9 as ligand. Active as Non-specific serine/threonine protein kinase, with EC number 2.7.11.1 Full crystallographic information is available from OCA.

Reference

Antiproliferative activity of olomoucine II, a novel 2,6,9-trisubstituted purine cyclin-dependent kinase inhibitor., Krystof V, McNae IW, Walkinshaw MD, Fischer PM, Muller P, Vojtesek B, Orsag M, Havlicek L, Strnad M, Cell Mol Life Sci. 2005 Aug;62(15):1763-71. PMID:16003486

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