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[[Image:3f3v.png|left|200px]]
==Kinase domain of cSrc in complex with inhibitor RL45 (Type II)==
<StructureSection load='3f3v' size='340' side='right' caption='[[3f3v]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3f3v]] 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=3F3V OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3F3V FirstGlance]. <br>
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1BU:1-{4-[(6-AMINOQUINAZOLIN-4-YL)AMINO]PHENYL}-3-[3-TERT-BUTYL-1-(3-METHYLPHENYL)-1H-PYRAZOL-5-YL]UREA'>1BU</scene><br>
<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2qlq|2qlq]], [[2qi8|2qi8]], [[2qq7|2qq7]], [[3f3t|3f3t]], [[3f3u|3f3u]], [[3f3w|3f3w]]</td></tr>
<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>
<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=3f3v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3f3v OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3f3v RCSB], [http://www.ebi.ac.uk/pdbsum/3f3v PDBsum]</span></td></tr>
<table>
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/f3/3f3v_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</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].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The emergence of drug resistance remains a fundamental challenge in the development of kinase inhibitors that are effective over long-term treatments. Allosteric inhibitors that bind to sites lying outside the highly conserved ATP pocket are thought to be more selective than ATP-competitive inhibitors and may circumvent some mechanisms of drug resistance. Crystal structures of type I and allosteric type III inhibitors in complex with the tyrosine kinase cSrc allowed us to employ principles of structure-based design to develop these scaffolds into potent type II kinase inhibitors. One of these compounds, 3c (RL46), disrupts FAK-mediated focal adhesions in cancer cells via direct inhibition of cSrc. Details gleaned from crystal structures revealed a key feature of a subset of these compounds, a surprising flexibility in the vicinity of the gatekeeper residue that allows these compounds to overcome a dasatinib-resistant gatekeeper mutation emerging in cSrc.


{{STRUCTURE_3f3v|  PDB=3f3v  |  SCENE=  }}
Hybrid compound design to overcome the gatekeeper T338M mutation in cSrc.,Getlik M, Grutter C, Simard JR, Kluter S, Rabiller M, Rode HB, Robubi A, Rauh D J Med Chem. 2009 Jul 9;52(13):3915-26. PMID:19462975<ref>PMID:19462975</ref>


===Kinase domain of cSrc in complex with inhibitor RL45 (Type II)===
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 
</div>
{{ABSTRACT_PUBMED_19462975}}
 
==About this Structure==
[[3f3v]] 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=3F3V OCA].


==See Also==
==See Also==
*[[Proto-oncogene tyrosine-protein kinase|Proto-oncogene tyrosine-protein kinase]]
*[[Tyrosine kinase|Tyrosine kinase]]
 
== References ==
==Reference==
<references/>
<ref group="xtra">PMID:019462975</ref><references group="xtra"/>
__TOC__
</StructureSection>
[[Category: Gallus gallus]]
[[Category: Gallus gallus]]
[[Category: Non-specific protein-tyrosine kinase]]
[[Category: Non-specific protein-tyrosine kinase]]
Retrieved from "https://proteopedia.org/3f3v"