2rku

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spinqualitylabelsall models 2rku, resolution 1.950Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

Structure of PLK1 in complex with BI2536

Overview

Polo-like kinase 1 is an important regulator of cell cycle progression, whose over-expression is often associated with oncogenesis. Polo-like, kinase 1 hence represents an attractive target for cancer intervention. BI, 2536 (Boehringer Ingelheim, Ingelheim, Germany), a Polo-like kinase 1, inhibitor currently in clinical trials, exhibits nanomolar potency against, Polo-like kinase isoforms and high selectivity against other kinases. We, have previously published the crystal structures of the Polo-like kinase 1, domain in complex with AMPPNP and an Aurora A inhibitor. In this work, we, present the co-crystal structure of Polo-like kinase 1 with BI 2536. The, structure, in combination with selectivity data for BI 2536 and related, compounds, illustrates important features for potency and selectivity. In, particular, we show that the methoxy group of BI 2536 is an important, specificity determinant against non-Polo-like kinases by taking advantage, of a small pocket generated by Leu 132 in the hinge region of Polo-like, kinase 1. The work presented here provides a framework for structure-based, drug design of Polo-like kinase 1-specific inhibitors.

About this Structure

2RKU is a Single protein structure of sequence from Homo sapiens with , , , and as ligands. Active as Polo kinase, with EC number 2.7.11.21 Known structural/functional Sites: , , , , , and . Full crystallographic information is available from OCA.

Reference

Selectivity-determining residues in Plk1., Kothe M, Kohls D, Low S, Coli R, Rennie GR, Feru F, Kuhn C, Ding YH, Chem Biol Drug Des. 2007 Dec;70(6):540-6. Epub 2007 Nov 13. PMID:18005335

Page seeded by OCA on Wed Feb 6 17:24:31 2008