2jko: Difference between revisions

← Older edit Newer edit →

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
-[[Image:2jko.png|left|200px]]
+==FOCAL ADHESION KINASE CATALYTIC DOMAIN IN COMPLEX WITH BIS-ANILINO PYRIMIDINE INHIBITOR==
+<StructureSection load='2jko' size='340' side='right' caption='[[2jko]], [[Resolution|resolution]] 1.65&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[2jko]] is a 1 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=2JKO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2JKO FirstGlance]. <br>
+</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BIJ:7-{[(2Z,5S)-5-CHLORO-2-{[2-METHOXY-4-(4-METHYLPIPERAZIN-1-YL)PHENYL]IMINO}-2,5-DIHYDROPYRIMIDIN-4-YL]AMINO}-2-METHYL-2,3-DIHYDRO-1H-ISOINDOL-1-ONE'>BIJ</scene><br>
+<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1ktm|1ktm]], [[2jkk|2jkk]], [[2j0k|2j0k]], [[1pv3|1pv3]], [[2j0l|2j0l]], [[2j0m|2j0m]], [[2j0j|2j0j]], [[2jkm|2jkm]], [[1qvx|1qvx]], [[2al6|2al6]], [[2aeh|2aeh]], [[2jkq|2jkq]]</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=2jko FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2jko OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2jko RCSB], [http://www.ebi.ac.uk/pdbsum/2jko 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/jk/2jko_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 ==
+Focal Adhesion Kinase (FAK) is a non-receptor tyrosine kinase required for cell migration, proliferation and survival. FAK overexpression has been documented in diverse human cancers and is associated with a poor clinical outcome. Recently, a novel bis-anilino pyrimidine inhibitor, TAE226, was reported to efficiently inhibit FAK signaling, arrest tumor growth and invasion and prolong the life of mice with glioma or ovarian tumor implants. Here we describe the crystal structures of the FAK kinase bound to TAE226 and three related bis-anilino pyrimidine compounds. TAE226 induces a conformation of the N-terminal portion of the kinase activation loop that is only observed in FAK, but is distinct from the conformation in both the active and inactive states of the kinase. This conformation appears to require a glycine immediately N-terminal to the "DFG motif", which adopts a helical conformation stabilized by interactions with TAE226. The presence of a glycine residue in this position contributes to the specificity of TAE226 and related compounds for FAK. Our work highlights the fact that kinases can access conformational space that is not necessarily utilized for their native catalytic regulation, and that such conformations can explain and be exploited for inhibitor specificity.
-{{STRUCTURE_2jko|  PDB=2jko  |  SCENE=  }}
+Crystal structures of the FAK kinase in complex with TAE226 and related bis-anilino pyrimidine inhibitors reveal a helical DFG conformation.,Lietha D, Eck MJ PLoS ONE. 2008;3(11):e3800. Epub 2008 Nov 24. PMID:19030106<ref>PMID:19030106</ref>
-===FOCAL ADHESION KINASE CATALYTIC DOMAIN IN COMPLEX WITH BIS-ANILINO PYRIMIDINE INHIBITOR===
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
-{{ABSTRACT_PUBMED_19030106}}
-==About this Structure==
-[[2jko]] is a 1 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=2JKO OCA].
 ==See Also==
 *[[Focal adhesion kinase|Focal adhesion kinase]]
+== References ==
-==Reference==
+<references/>
-<ref group="xtra">PMID:019030106</ref><references group="xtra"/>
+__TOC__
+</StructureSection>
 [[Category: Gallus gallus]]
 [[Category: Non-specific protein-tyrosine kinase]]