2gfs: Difference between revisions

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-[[Image:2gfs.png|left|200px]]
+==P38 Kinase Crystal Structure in complex with RO3201195==
+<StructureSection load='2gfs' size='340' side='right' caption='[[2gfs]], [[Resolution|resolution]] 1.75&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[2gfs]] 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=2GFS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2GFS FirstGlance]. <br>
+</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=PQB:[5-AMINO-1-(4-FLUOROPHENYL)-1H-PYRAZOL-4-YL](3-{[(2R)-2,3-DIHYDROXYPROPYL]OXY}PHENYL)METHANONE'>PQB</scene><br>
+<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MAPK14, CSBP, CSBP1, CSBP2, 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/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </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=2gfs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2gfs OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2gfs RCSB], [http://www.ebi.ac.uk/pdbsum/2gfs 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/gf/2gfs_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 ==
+A novel class of highly selective inhibitors of p38 MAP kinase was discovered from high throughput screening. The synthesis and optimization of a series of 5-amino-N-phenyl-1H-pyrazol-4-yl-3-phenylmethanones is described. An X-ray crystal structure of this series bound in the ATP binding pocket of unphosphorylated p38alpha established the presence of a unique hydrogen bond between the exocyclic amine of the inhibitor and threonine 106 which likely contributes to the selectivity for p38. The crystallographic information was used to optimize the potency and physicochemical properties of the series. The incorporation of the 2,3-dihydroxypropoxy moiety on the pyrazole scaffold resulted in a compound with excellent drug-like properties including high oral bioavailability. These efforts identified 63 (RO3201195) as an orally bioavailable and highly selective inhibitor of p38 which was selected for advancement into Phase I clinical trials.
-{{STRUCTURE_2gfs|  PDB=2gfs  |  SCENE=  }}
+Discovery of S-[5-amino-1-(4-fluorophenyl)-1H-pyrazol-4-yl]-[3-(2,3-dihydroxypropoxy)ph enyl]methanone (RO3201195), an orally bioavailable and highly selective inhibitor of p38 MAP kinase.,Goldstein DM, Alfredson T, Bertrand J, Browner MF, Clifford K, Dalrymple SA, Dunn J, Freire-Moar J, Harris S, Labadie SS, La Fargue J, Lapierre JM, Larrabee S, Li F, Papp E, McWeeney D, Ramesha C, Roberts R, Rotstein D, San Pablo B, Sjogren EB, So OY, Talamas FX, Tao W, Trejo A, Villasenor A, Welch M, Welch T, Weller P, Whiteley PE, Young K, Zipfel S J Med Chem. 2006 Mar 9;49(5):1562-75. PMID:16509574<ref>PMID:16509574</ref>
-===P38 Kinase Crystal Structure in complex with RO3201195===
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
-{{ABSTRACT_PUBMED_16509574}}
-==About this Structure==
-[[2gfs]] 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=2GFS OCA].
 ==See Also==
 *[[Mitogen-activated protein kinase|Mitogen-activated protein kinase]]
+== References ==
-==Reference==
+<references/>
-<ref group="xtra">PMID:016509574</ref><references group="xtra"/>
+__TOC__
+</StructureSection>
 [[Category: Homo sapiens]]
 [[Category: Non-specific serine/threonine protein kinase]]