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Analysis of water patterns in protein kinase binding sites

✍ Scribed by Caterina Barillari; Anna L. Duncan; Isaac M. Westwood; Julian Blagg; Rob L. M. van Montfort

Book ID
105358248
Publisher
John Wiley and Sons
Year
2011
Tongue
English
Weight
478 KB
Volume
79
Category
Article
ISSN
0887-3585

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✦ Synopsis

Abstract

Deregulation of protein kinases is associated with numerous diseases, making them important targets for drug discovery. The majority of drugs target the catalytic site of these proteins, but due to the high level of similarity within the ATP binding sites of protein kinases, it is often difficult to achieve the required pharmacological selectivity. In this study, we describe the identification and subsequent analysis of water patterns in the ATP binding sites of 171 protein kinase structures, comprising 19 different kinases from various branches of the kinome, and demonstrate that structurally similar binding sites often have significantly different water patterns. We show that the observed variations in water patterns of different, but structurally similar kinases can be exploited in the structure‐based design of potent and selective kinase inhibitors. Proteins 2011; Β© 2011 Wiley‐Liss, Inc.

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