1kkq
From Proteopedia
(Difference between revisions)
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- | + | ==Crystal structure of the human PPAR-alpha ligand-binding domain in complex with an antagonist GW6471 and a SMRT corepressor motif== | |
- | + | <StructureSection load='1kkq' size='340' side='right' caption='[[1kkq]], [[Resolution|resolution]] 3.00Å' scene=''> | |
- | {{ | + | == Structural highlights == |
+ | <table><tr><td colspan='2'>[[1kkq]] is a 8 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=1KKQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1KKQ FirstGlance]. <br> | ||
+ | </td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=471:N-((2S)-2-({(1Z)-1-METHYL-3-OXO-3-[4-(TRIFLUOROMETHYL)+PHENYL]PROP-1-ENYL}AMINO)-3-{4-[2-(5-METHYL-2-PHENYL-1,3-OXAZOL-4-YL)ETHOXY]PHENYL}PROPYL)PROPANAMIDE'>471</scene><br> | ||
+ | <tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1k7l|1k7l]], [[1k74|1k74]]</td></tr> | ||
+ | <tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">human ([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>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1kkq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1kkq OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1kkq RCSB], [http://www.ebi.ac.uk/pdbsum/1kkq 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/kk/1kkq_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 == | ||
+ | Repression of gene transcription by nuclear receptors is mediated by interactions with co-repressor proteins such as SMRT and N-CoR, which in turn recruit histone deacetylases to the chromatin. Aberrant interactions between nuclear receptors and co-repressors contribute towards acute promyelocytic leukaemia and thyroid hormone resistance syndrome. The binding of co-repressors to nuclear receptors occurs in the unliganded state, and can be stabilized by antagonists. Here we report the crystal structure of a ternary complex containing the peroxisome proliferator-activated receptor-alpha ligand-binding domain bound to the antagonist GW6471 and a SMRT co-repressor motif. In this structure, the co-repressor motif adopts a three-turn alpha-helix that prevents the carboxy-terminal activation helix (AF-2) of the receptor from assuming the active conformation. Binding of the co-repressor motif is further reinforced by the antagonist, which blocks the AF-2 helix from adopting the active position. Biochemical analyses and structure-based mutagenesis indicate that this mode of co-repressor binding is highly conserved across nuclear receptors. | ||
- | + | Structural basis for antagonist-mediated recruitment of nuclear co-repressors by PPARalpha.,Xu HE, Stanley TB, Montana VG, Lambert MH, Shearer BG, Cobb JE, McKee DD, Galardi CM, Plunket KD, Nolte RT, Parks DJ, Moore JT, Kliewer SA, Willson TM, Stimmel JB Nature. 2002 Feb 14;415(6873):813-7. PMID:11845213<ref>PMID:11845213</ref> | |
- | + | ||
- | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
- | + | </div> | |
==See Also== | ==See Also== | ||
*[[Peroxisome Proliferator-Activated Receptors|Peroxisome Proliferator-Activated Receptors]] | *[[Peroxisome Proliferator-Activated Receptors|Peroxisome Proliferator-Activated Receptors]] | ||
- | + | == References == | |
- | == | + | <references/> |
- | + | __TOC__ | |
+ | </StructureSection> | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Cobb, J E.]] | [[Category: Cobb, J E.]] |
Revision as of 04:09, 3 October 2014
Crystal structure of the human PPAR-alpha ligand-binding domain in complex with an antagonist GW6471 and a SMRT corepressor motif
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