3hec: Difference between revisions

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-[[Image:3hec.png|left|200px]]
+==P38 in complex with Imatinib==
+<StructureSection load='3hec' size='340' side='right' caption='[[3hec]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[3hec]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3HEC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3HEC FirstGlance]. <br>
+</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BOG:B-OCTYLGLUCOSIDE'>BOG</scene>, <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><br>
+<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3heg|3heg]]</td></tr>
+<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CSBP, CSBP1, CSBP2, CSPB1, MAPK14, MXI2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
+<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Mitogen-activated_protein_kinase Mitogen-activated protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.24 2.7.11.24] </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=3hec FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3hec OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3hec RCSB], [http://www.ebi.ac.uk/pdbsum/3hec 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/he/3hec_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 ==
+Protein kinases c-Abl, b-Raf, and p38alpha are recognized as important targets for therapeutic intervention. c-Abl and b-Raf are major targets of marketed oncology drugs Imatinib (Gleevec) and Sorafenib (Nexavar), respectively, and BIRB-796 is a p38alpha inhibitor that reached Phase II clinical trials. A shared feature of these drugs is the fact that they bind to the DFG-out forms of their kinase targets. Although the discovery of this class of kinase inhibitors has increased the level of emphasis on the design of DFG-out inhibitors, the structural determinants for their binding and stabilization of the DFG-out conformation remain unclear. To improve our understanding of these determinants, we determined cocrystal structures of Imatinib and Sorafenib with p38alpha. We also conducted a detailed analysis of Imatinib and Sorafenib binding to p38alpha in comparison with BIRB-796, including binding kinetics, binding interactions, the solvent accessible surface area (SASA) of the ligands, and stabilization of key structural elements of the protein upon ligand binding. Our results yield an improved understanding of the structural requirements for stabilizing the DFG-out form and a rationale for understanding the genesis of ligand selectivity among DFG-out inhibitors of protein kinases.
-{{STRUCTURE_3hec|  PDB=3hec  |  SCENE=  }}
+Analysis of imatinib and sorafenib binding to p38alpha compared with c-Abl and b-Raf provides structural insights for understanding the selectivity of inhibitors targeting the DFG-out form of protein kinases.,Namboodiri HV, Bukhtiyarova M, Ramcharan J, Karpusas M, Lee Y, Springman EB Biochemistry. 2010 May 4;49(17):3611-8. PMID:20337484<ref>PMID:20337484</ref>
-===P38 in complex with Imatinib===
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
-{{ABSTRACT_PUBMED_20337484}}
-==About this Structure==
-[[3hec]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3HEC OCA].
 ==See Also==
 *[[Mitogen-activated protein kinase|Mitogen-activated protein kinase]]
+== References ==
-==Reference==
+<references/>
-<ref group="xtra">PMID:020337484</ref><references group="xtra"/>
+__TOC__
+</StructureSection>
 [[Category: Homo sapiens]]
 [[Category: Mitogen-activated protein kinase]]