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[[Image: | ==Crystal Structure of Human p38alpha complexed with a pyrimidopyridazinone compound== | ||
<StructureSection load='3hp5' size='340' side='right' caption='[[3hp5]], [[Resolution|resolution]] 2.30Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3hp5]] 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=3HP5 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3HP5 FirstGlance]. <br> | |||
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=52P:5-(2,6-DICHLOROPHENYL)-2-[(2,4-DIFLUOROPHENYL)SULFANYL]-6H-PYRIMIDO[1,6-B]PYRIDAZIN-6-ONE'>52P</scene>, <scene name='pdbligand=I46:2-FLUORO-4-[4-(4-FLUOROPHENYL)-1H-PYRAZOL-3-YL]PYRIDINE'>I46</scene><br> | |||
<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3hll|3hll]], [[3hp2|3hp2]]</td></tr> | |||
<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CSBP, CSBP1, CSBP2, CSPB1, MAPK14, MXI2, THP-1 ([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=3hp5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3hp5 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3hp5 RCSB], [http://www.ebi.ac.uk/pdbsum/3hp5 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/hp/3hp5_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 identification and evolution of a series of potent and selective p38 inhibitors is described. p38 inhibitors based on a N-benzyl pyridinone high-throughput screening hit were prepared and their SAR explored. Their design was guided by ligand bound co-crystals of p38alpha. These efforts resulted in the identification of 12r and 19 as orally active inhibitors of p38 with significant efficacy in both acute and chronic models of inflammation. | |||
Discovery of N-substituted pyridinones as potent and selective inhibitors of p38 kinase.,Selness SR, Devraj RV, Monahan JB, Boehm TL, Walker JK, Devadas B, Durley RC, Kurumbail R, Shieh H, Xing L, Hepperle M, Rucker PV, Jerome KD, Benson AG, Marrufo LD, Madsen HM, Hitchcock J, Owen TJ, Christie L, Promo MA, Hickory BS, Alvira E, Naing W, Blevis-Bal R Bioorg Med Chem Lett. 2009 Oct 15;19(20):5851-6. Epub 2009 Aug 27. PMID:19751974<ref>PMID:19751974</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
==See Also== | ==See Also== | ||
*[[Mitogen-activated protein kinase|Mitogen-activated protein kinase]] | *[[Mitogen-activated protein kinase|Mitogen-activated protein kinase]] | ||
== References == | |||
== | <references/> | ||
< | __TOC__ | ||
</StructureSection> | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Mitogen-activated protein kinase]] | [[Category: Mitogen-activated protein kinase]] | ||
Revision as of 15:31, 29 September 2014
Crystal Structure of Human p38alpha complexed with a pyrimidopyridazinone compoundCrystal Structure of Human p38alpha complexed with a pyrimidopyridazinone compound
Structural highlights
Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe identification and evolution of a series of potent and selective p38 inhibitors is described. p38 inhibitors based on a N-benzyl pyridinone high-throughput screening hit were prepared and their SAR explored. Their design was guided by ligand bound co-crystals of p38alpha. These efforts resulted in the identification of 12r and 19 as orally active inhibitors of p38 with significant efficacy in both acute and chronic models of inflammation. Discovery of N-substituted pyridinones as potent and selective inhibitors of p38 kinase.,Selness SR, Devraj RV, Monahan JB, Boehm TL, Walker JK, Devadas B, Durley RC, Kurumbail R, Shieh H, Xing L, Hepperle M, Rucker PV, Jerome KD, Benson AG, Marrufo LD, Madsen HM, Hitchcock J, Owen TJ, Christie L, Promo MA, Hickory BS, Alvira E, Naing W, Blevis-Bal R Bioorg Med Chem Lett. 2009 Oct 15;19(20):5851-6. Epub 2009 Aug 27. PMID:19751974[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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