3gfe

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[[Image:3gfe.png|left|200px]]
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==Crystal Structure of p38a Mitogen-Activated Protein Kinase in Complex with a Pyrazolopyridinone Inhibitor==
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<StructureSection load='3gfe' size='340' side='right' caption='[[3gfe]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[3gfe]] 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=3GFE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3GFE FirstGlance]. <br>
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</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=P37:N-CYCLOPROPYL-3-{[1-(2,4-DIFLUOROPHENYL)-7-METHYL-6-OXO-6,7-DIHYDRO-1H-PYRAZOLO[3,4-B]PYRIDIN-4-YL]AMINO}-4-METHYLBENZAMIDE'>P37</scene><br>
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<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1yqj|1yqj]], [[3dt1|3dt1]], [[3ds6|3ds6]]</td></tr>
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<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MAPK14, CSBP, CSBP1, CSBP2, CSPB1, MXI2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
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<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>
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<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=3gfe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3gfe OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3gfe RCSB], [http://www.ebi.ac.uk/pdbsum/3gfe PDBsum]</span></td></tr>
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<table>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/gf/3gfe_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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A novel class of fused pyrazole-derived inhibitors of p38alpha mitogen-activated protein kinase (MAPK) is disclosed. These inhibitors were evaluated for their ability to inhibit the p38alpha enzyme, the secretion of TNFalpha in a LPS-challenged THP1 cell line and TNFalpha-induced production of IL-8 in 50% human whole blood. This series was optimized through a SAR investigation to provide inhibitors with IC(50) values in the low single-digit nanomolar range in whole blood. Further investigation of their pharmacokinetic profiles led to the identification of two potent and orally bioavailable p38 inhibitors 10 m and 10 q. Inhibitor 10 m was found to be efficacious in vivo in the inhibition of TNFalpha production in LPS-stimulated Lewis rats with an ED(50) of 0.1mg/kg while 10 q was found to have an ED(50) of 0.05-0.07 mg/kg.
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{{STRUCTURE_3gfe| PDB=3gfe | SCENE= }}
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Part 1: Structure-Activity Relationship (SAR) investigations of fused pyrazoles as potent, selective and orally available inhibitors of p38alpha mitogen-activated protein kinase.,Wurz RP, Pettus LH, Xu S, Henkle B, Sherman L, Plant M, Miner K, McBride H, Wong LM, Saris CJ, Lee MR, Chmait S, Mohr C, Hsieh F, Tasker AS Bioorg Med Chem Lett. 2009 Aug 15;19(16):4724-8. Epub 2009 Jun 17. PMID:19574047<ref>PMID:19574047</ref>
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===Crystal Structure of p38a Mitogen-Activated Protein Kinase in Complex with a Pyrazolopyridinone Inhibitor===
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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{{ABSTRACT_PUBMED_19574047}}
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==About this Structure==
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[[3gfe]] 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=3GFE OCA].
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==See Also==
==See Also==
*[[Mitogen-activated protein kinase|Mitogen-activated protein kinase]]
*[[Mitogen-activated protein kinase|Mitogen-activated protein kinase]]
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== References ==
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==Reference==
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<references/>
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<ref group="xtra">PMID:019574047</ref><references group="xtra"/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Mitogen-activated protein kinase]]
[[Category: Mitogen-activated protein kinase]]

Revision as of 12:36, 29 September 2014

Crystal Structure of p38a Mitogen-Activated Protein Kinase in Complex with a Pyrazolopyridinone Inhibitor

3gfe, resolution 2.10Å

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