3dqw

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[[Image:3dqw.png|left|200px]]
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==c-Src kinase domain Thr338Ile mutant in complex with ATPgS==
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<StructureSection load='3dqw' size='340' side='right' caption='[[3dqw]], [[Resolution|resolution]] 2.02&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[3dqw]] is a 4 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=3DQW OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3DQW FirstGlance]. <br>
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</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AGS:PHOSPHOTHIOPHOSPHORIC+ACID-ADENYLATE+ESTER'>AGS</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene><br>
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<tr><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene></td></tr>
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<tr><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>
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<tr><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>
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<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3dqw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3dqw OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3dqw RCSB], [http://www.ebi.ac.uk/pdbsum/3dqw PDBsum]</span></td></tr>
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<table>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/dq/3dqw_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Protein kinases targeted by small-molecule inhibitors develop resistance through mutation of the 'gatekeeper' threonine residue of the active site. Here we show that the gatekeeper mutation in the cellular forms of c-ABL, c-SRC, platelet-derived growth factor receptor-alpha and -beta, and epidermal growth factor receptor activates the kinase and promotes malignant transformation of BaF3 cells. Structural analysis reveals that a network of hydrophobic interactions-the hydrophobic spine-characteristic of the active kinase conformation is stabilized by the gatekeeper substitution. Substitution of glycine for the residues constituting the spine disrupts the hydrophobic connectivity and inactivates the kinase. Furthermore, a small-molecule inhibitor that maximizes complementarity with the dismantled spine (compound 14) inhibits the gatekeeper mutation of BCR-ABL-T315I. These results demonstrate that mutation of the gatekeeper threonine is a common mechanism of activation for tyrosine kinases and provide structural insights to guide the development of next-generation inhibitors.
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{{STRUCTURE_3dqw| PDB=3dqw | SCENE= }}
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Activation of tyrosine kinases by mutation of the gatekeeper threonine.,Azam M, Seeliger MA, Gray NS, Kuriyan J, Daley GQ Nat Struct Mol Biol. 2008 Oct;15(10):1109-18. Epub 2008 Sep 14. PMID:18794843<ref>PMID:18794843</ref>
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===c-Src kinase domain Thr338Ile mutant in complex with ATPgS===
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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{{ABSTRACT_PUBMED_18794843}}
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==About this Structure==
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[[3dqw]] is a 4 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=3DQW OCA].
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==See Also==
==See Also==
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*[[Proto-oncogene tyrosine-protein kinase|Proto-oncogene tyrosine-protein kinase]]
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*[[Tyrosine kinase|Tyrosine kinase]]
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== References ==
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==Reference==
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<references/>
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<ref group="xtra">PMID:018794843</ref><references group="xtra"/>
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__TOC__
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</StructureSection>
[[Category: Gallus gallus]]
[[Category: Gallus gallus]]
[[Category: Non-specific protein-tyrosine kinase]]
[[Category: Non-specific protein-tyrosine kinase]]

Revision as of 11:01, 29 September 2014

c-Src kinase domain Thr338Ile mutant in complex with ATPgS

3dqw, resolution 2.02Å

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