2pl0
From Proteopedia
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==About this Structure== | ==About this Structure== | ||
| - | 2PL0 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=STI:'>STI</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Non-specific_protein-tyrosine_kinase Non-specific protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.2 2.7.10.2] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2PL0 OCA]. | + | 2PL0 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=STI:'>STI</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Non-specific_protein-tyrosine_kinase Non-specific protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.2 2.7.10.2] Known structural/functional Site: <scene name='pdbsite=AC1:Sti+Binding+Site+For+Residue+A+200'>AC1</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2PL0 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: transferase]] | [[Category: transferase]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Feb 27 07:48:00 2008'' |
Revision as of 05:48, 27 February 2008
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LCK bound to imatinib
Contents |
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 2008. (c) 2007 Wiley-Liss, Inc.
Disease
Known disease associated with this structure: SCID due to LCK deficiency OMIM:[153390]
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 Known structural/functional Site: . 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;70(4):1451-1460. PMID:17910071
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