2c5y

From Proteopedia

Revision as of 08:31, 3 February 2008

DIFFERENTIAL BINDING OF INHIBITORS TO ACTIVE AND INACTIVE CDK2 PROVIDES INSIGHTS FOR DRUG DESIGN

Overview

The cyclin-dependent kinases (CDKs) have been characterized in complex, with a variety of inhibitors, but the majority of structures solved are in, the inactive form. We have solved the structures of six inhibitors in both, the monomeric CDK2 and binary CDK2/cyclinA complexes and demonstrate that, significant differences in ligand binding occur depending on the, activation state. The binding mode of two ligands in particular varies, substantially in active and inactive CDK2. Furthermore, energetic analysis, of CDK2/cyclin/inhibitors demonstrates that a good correlation exists, between the in vitro potency and the calculated energies of interaction, but no such relationship exists for CDK2/inhibitor structures. These, results confirm that monomeric CDK2 ligand complexes do not fully reflect, active conformations, revealing significant implications for inhibitor, design while also suggesting that the monomeric CDK2 conformation can be, selectively inhibited.

About this Structure

2C5Y is a Single protein structure of sequence from Homo sapiens with as ligand. Active as Transferred entry: 2.7.11.1, with EC number 2.7.1.37 Known structural/functional Site: . Full crystallographic information is available from OCA.

Reference

Differential binding of inhibitors to active and inactive CDK2 provides insights for drug design., Kontopidis G, McInnes C, Pandalaneni SR, McNae I, Gibson D, Mezna M, Thomas M, Wood G, Wang S, Walkinshaw MD, Fischer PM, Chem Biol. 2006 Feb;13(2):201-11. PMID:16492568

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