2pl0: Difference between revisions
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'''LCK bound to imatinib''' | '''LCK bound to imatinib''' | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Jacobs, M D.]] | [[Category: Jacobs, M D.]] | ||
[[Category: | [[Category: Kinase phosphorylation]] | ||
[[Category: | [[Category: Transferase]] | ||
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Revision as of 13:19, 4 May 2008
LCK bound to imatinib
OverviewOverview
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 2008. (c) 2007 Wiley-Liss, Inc.
DiseaseDisease
Known disease associated with this structure: SCID due to LCK deficiency OMIM:[153390]
About this StructureAbout this Structure
2PL0 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
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;70(4):1451-1460. PMID:17910071 Page seeded by OCA on Sun May 4 13:19:48 2008