2pl0
From Proteopedia
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LCK bound to imatinib
Overview
We report a clustering of public human protein kinase structures based on, the conformations of two structural elements, the activation segment and, the C-helix, revealing three discrete clusters. One cluster includes, kinases in catalytically active conformations. Each of the other clusters, contains a distinct inactive conformation. Typically, kinases adopt at, most one of the inactive conformations in available X-ray structures, implying that one of the conformations is preferred for many kinases. The, classification is consistent with selectivity profiles of several, well-characterized kinase inhibitors. We show further that inhibitor, selectivity profiles guide kinase classification. For example, selective, inhibition of lck among src-family kinases by imatinib (Gleevec) suggests, that the relative stabilities of inactive conformations of lck are, different from other src-family kinases. We report the X-ray structure of, the lck/imatinib complex, confirming that the conformation adopted by lck, is distinct from other structurally-characterized src-family kinases and, instead resembles kinases abl1 and kit in complex with imatinib. Our, classification creates new paths for designing small-molecule inhibitors., Proteins 2007. (c) 2007 Wiley-Liss, Inc.
About this Structure
2PL0 is a Single protein structure of sequence from Homo sapiens with as ligand. Active as Non-specific protein-tyrosine kinase, with EC number 2.7.10.2 Full crystallographic information is available from OCA.
Reference
Classifying protein kinase structures guides use of ligand-selectivity profiles to predict inactive conformations: Structure of lck/imatinib complex., Jacobs MD, Caron PR, Hare BJ, Proteins. 2007 Oct 1;. PMID:17910071
Page seeded by OCA on Wed Jan 23 12:04:55 2008
