2pl0
From Proteopedia
(New page: 200px<br /> <applet load="2pl0" size="450" color="white" frame="true" align="right" spinBox="true" caption="2pl0, resolution 2.800Å" /> '''LCK bound to imati...) |
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| - | [[Image:2pl0. | + | [[Image:2pl0.jpg|left|200px]]<br /><applet load="2pl0" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="2pl0" size=" | + | |
caption="2pl0, resolution 2.800Å" /> | caption="2pl0, resolution 2.800Å" /> | ||
'''LCK bound to imatinib'''<br /> | '''LCK bound to imatinib'''<br /> | ||
| - | == | + | ==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== | ==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 STI 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:// | + | 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]. |
| + | |||
| + | ==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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17910071 17910071] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Non-specific protein-tyrosine kinase]] | [[Category: Non-specific protein-tyrosine kinase]] | ||
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[[Category: transferase]] | [[Category: transferase]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 12:04:55 2008'' |
Revision as of 10:04, 23 January 2008
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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
