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2pl0
From Proteopedia
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|SITE= <scene name='pdbsite=AC1:Sti+Binding+Site+For+Residue+A+200'>AC1</scene> | |SITE= <scene name='pdbsite=AC1:Sti+Binding+Site+For+Residue+A+200'>AC1</scene> | ||
|LIGAND= <scene name='pdbligand=STI:4-(4-METHYL-PIPERAZIN-1-YLMETHYL)-N-[4-METHYL-3-(4-PYRIDIN-3-YL-PYRIMIDIN-2-YLAMINO)-PHENYL]-BENZAMIDE'>STI</scene> | |LIGAND= <scene name='pdbligand=STI:4-(4-METHYL-PIPERAZIN-1-YLMETHYL)-N-[4-METHYL-3-(4-PYRIDIN-3-YL-PYRIMIDIN-2-YLAMINO)-PHENYL]-BENZAMIDE'>STI</scene> | ||
| - | |ACTIVITY= [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] | + | |ACTIVITY= <span class='plainlinks'>[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] </span> |
|GENE= LCK ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |GENE= LCK ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2pl0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2pl0 OCA], [http://www.ebi.ac.uk/pdbsum/2pl0 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2pl0 RCSB]</span> | ||
}} | }} | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Jacobs, M D.]] | [[Category: Jacobs, M D.]] | ||
| - | [[Category: STI]] | ||
[[Category: kinase phosphorylation]] | [[Category: kinase phosphorylation]] | ||
[[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 Mon Mar 31 04:37:21 2008'' |
Revision as of 01:37, 31 March 2008
| |||||||
| , resolution 2.800Å | |||||||
|---|---|---|---|---|---|---|---|
| Sites: | |||||||
| Ligands: | |||||||
| Gene: | LCK (Homo sapiens) | ||||||
| Activity: | Non-specific protein-tyrosine kinase, with EC number 2.7.10.2 | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
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. 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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