2v0d

From Proteopedia

Revision as of 21:34, 12 November 2007

CRYSTAL STRUCTURE OF HUMAN CDK2 COMPLEXED WITH A THIAZOLIDINONE INHIBITOR

Overview

Virtual screening against a pCDK2/cyclin A crystal structure led to the, identification of a potent and novel CDK2 inhibitor, which exhibited an, unusual mode of interaction with the kinase binding motif. With the aid of, X-ray crystallography and modelling, a medicinal chemistry strategy was, implemented to probe the interactions seen in the crystal structure and to, establish SAR. A fragment-based approach was also considered but a, different, more conventional, binding mode was observed. Compound, selectivity against GSK-3beta was improved using a rational design, strategy, with crystallographic verification of the CDK2 binding mode.

About this Structure

2V0D is a Single protein structure of sequence from Homo sapiens with CL and C53 as ligands. Structure known Active Site: AC1. Full crystallographic information is available from OCA.

Reference

Discovery of a potent CDK2 inhibitor with a novel binding mode, using virtual screening and initial, structure-guided lead scoping., Richardson CM, Nunns CL, Williamson DS, Parratt MJ, Dokurno P, Howes R, Borgognoni J, Drysdale MJ, Finch H, Hubbard RE, Jackson PS, Kierstan P, Lentzen G, Moore JD, Murray JB, Simmonite H, Surgenor AE, Torrance CJ, Bioorg Med Chem Lett. 2007 Jul 15;17(14):3880-5. Epub 2007 May 6. PMID:17570665

Page seeded by OCA on Mon Nov 12 23:41:09 2007