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[[ | ==Crystal structure of the L317I mutant of the C-src tyrosine kinase domain complexed with dasatinib== | ||
<StructureSection load='3qlg' size='340' side='right' caption='[[3qlg]], [[Resolution|resolution]] 2.75Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3qlg]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Gallus_gallus Gallus gallus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3QLG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3QLG FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1N1:N-(2-CHLORO-6-METHYLPHENYL)-2-({6-[4-(2-HYDROXYETHYL)PIPERAZIN-1-YL]-2-METHYLPYRIMIDIN-4-YL}AMINO)-1,3-THIAZOLE-5-CARBOXAMIDE'>1N1</scene></td></tr> | |||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3of0|3of0]], [[3oez|3oez]], [[3qlf|3qlf]], [[3g5d|3g5d]]</td></tr> | |||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SRC ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9031 Gallus gallus])</td></tr> | |||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><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></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3qlg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qlg OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3qlg RCSB], [http://www.ebi.ac.uk/pdbsum/3qlg PDBsum]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The cancer drug imatinib inhibits the tyrosine kinases c-Abl, c-Kit, and the PDGF receptor. Imatinib is less effective against c-Src, which is difficult to understand because residues interacting with imatinib in crystal structures of Abl and c-Kit are conserved in c-Src. The crystal structure of the c-Src kinase domain in complex with imatinib closely resembles that of Abl*imatinib and c-Kit*imatinib, and differs significantly from the inactive "Src/CDK" conformation of the Src family kinases. Attempts to increase the affinity of c-Src for imatinib by swapping residues with the corresponding residues in Abl have not been successful, suggesting that the thermodynamic penalty for adoption of the imatinib-binding conformation by c-Src is distributed over a broad region of the structure. Two mutations that are expected to destabilize the inactive Src/CDK conformation increase drug sensitivity 15-fold, suggesting that the free-energy balance between different inactive states is a key to imatinib binding. | |||
c-Src binds to the cancer drug imatinib with an inactive Abl/c-Kit conformation and a distributed thermodynamic penalty.,Seeliger MA, Nagar B, Frank F, Cao X, Henderson MN, Kuriyan J Structure. 2007 Mar;15(3):299-311. PMID:17355866<ref>PMID:17355866</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
==See Also== | ==See Also== | ||
*[[ | *[[Tyrosine kinase|Tyrosine kinase]] | ||
== References == | |||
== | <references/> | ||
< | __TOC__ | ||
</StructureSection> | |||
[[Category: Gallus gallus]] | [[Category: Gallus gallus]] | ||
[[Category: Non-specific protein-tyrosine kinase]] | [[Category: Non-specific protein-tyrosine kinase]] | ||
[[Category: Boubeva, R | [[Category: Boubeva, R]] | ||
[[Category: Pernot, L | [[Category: Pernot, L]] | ||
[[Category: Perozzo, R | [[Category: Perozzo, R]] | ||
[[Category: Scapozza, L | [[Category: Scapozza, L]] | ||
[[Category: C-src l317i mutant]] | [[Category: C-src l317i mutant]] | ||
[[Category: Dasatinib]] | [[Category: Dasatinib]] | ||
[[Category: Transferase]] | [[Category: Transferase]] | ||
[[Category: Tyrosine kinase]] | [[Category: Tyrosine kinase]] | ||
Revision as of 11:51, 9 December 2014
Crystal structure of the L317I mutant of the C-src tyrosine kinase domain complexed with dasatinib
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