1k7l

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{{STRUCTURE_1k7l| PDB=1k7l | SCENE= }}
 
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===The 2.5 Angstrom resolution crystal structure of the human PPARalpha ligand binding domain bound with GW409544 and a co-activator peptide.===
 
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{{ABSTRACT_PUBMED_11698662}}
 
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==Disease==
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==The 2.5 Angstrom resolution crystal structure of the human PPARalpha ligand binding domain bound with GW409544 and a co-activator peptide.==
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[[http://www.uniprot.org/uniprot/NCOA1_HUMAN NCOA1_HUMAN]] Note=A chromosomal aberration involving NCOA1 is a cause of rhabdomyosarcoma. Translocation t(2;2)(q35;p23) with PAX3 generates the NCOA1-PAX3 oncogene consisting of the N-terminus part of PAX3 and the C-terminus part of NCOA1. The fusion protein acts as a transcriptional activator. Rhabdomyosarcoma is the most common soft tissue carcinoma in childhood, representing 5-8% of all malignancies in children.
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<StructureSection load='1k7l' size='340' side='right'caption='[[1k7l]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
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== Structural highlights ==
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==Function==
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<table><tr><td colspan='2'>[[1k7l]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1K7L OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1K7L FirstGlance]. <br>
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[[http://www.uniprot.org/uniprot/NCOA1_HUMAN NCOA1_HUMAN]] Nuclear receptor coactivator that directly binds nuclear receptors and stimulates the transcriptional activities in a hormone-dependent fashion. Involved in the coactivation of different nuclear receptors, such as for steroids (PGR, GR and ER), retinoids (RXRs), thyroid hormone (TRs) and prostanoids (PPARs). Also involved in coactivation mediated by STAT3, STAT5A, STAT5B and STAT6 transcription factors. Displays histone acetyltransferase activity toward H3 and H4; the relevance of such activity remains however unclear. Plays a central role in creating multisubunit coactivator complexes that act via remodeling of chromatin, and possibly acts by participating in both chromatin remodeling and recruitment of general transcription factors. Required with NCOA2 to control energy balance between white and brown adipose tissues. Required for mediating steroid hormone response. Isoform 2 has a higher thyroid hormone-dependent transactivation activity than isoform 1 and isoform 3.<ref>PMID:9427757</ref><ref>PMID:7481822</ref><ref>PMID:9223431</ref><ref>PMID:9296499</ref><ref>PMID:9223281</ref><ref>PMID:10449719</ref><ref>PMID:12954634</ref>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.5&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=544:2-(1-METHYL-3-OXO-3-PHENYL-PROPYLAMINO)-3-{4-[2-(5-METHYL-2-PHENYL-OXAZOL-4-YL)-ETHOXY]-PHENYL}-PROPIONIC+ACID'>544</scene>, <scene name='pdbligand=YT3:YTTRIUM+(III)+ION'>YT3</scene></td></tr>
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==About this Structure==
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1k7l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1k7l OCA], [https://pdbe.org/1k7l PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1k7l RCSB], [https://www.ebi.ac.uk/pdbsum/1k7l PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1k7l ProSAT]</span></td></tr>
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[[1k7l]] 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=1K7L OCA].
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/PPARA_HUMAN PPARA_HUMAN] Ligand-activated transcription factor. Key regulator of lipid metabolism. Activated by the endogenous ligand 1-palmitoyl-2-oleoyl-sn-glycerol-3-phosphocholine (16:0/18:1-GPC). Activated by oleylethanolamide, a naturally occurring lipid that regulates satiety (By similarity). Receptor for peroxisome proliferators such as hypolipidemic drugs and fatty acids. Regulates the peroxisomal beta-oxidation pathway of fatty acids. Functions as transcription activator for the ACOX1 and P450 genes. Transactivation activity requires heterodimerization with RXRA and is antagonized by NR2C2.<ref>PMID:7684926</ref> <ref>PMID:7629123</ref> <ref>PMID:9556573</ref> <ref>PMID:10195690</ref>
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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/k7/1k7l_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/main_output.php?pdb_ID=1k7l ConSurf].
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<div style="clear:both"></div>
==See Also==
==See Also==
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*[[Peroxisome Proliferator-Activated Receptors|Peroxisome Proliferator-Activated Receptors]]
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*[[Peroxisome proliferator-activated receptor 3D structures|Peroxisome proliferator-activated receptor 3D structures]]
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== References ==
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==Reference==
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<references/>
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<ref group="xtra">PMID:011698662</ref><ref group="xtra">PMID:011845213</ref><references group="xtra"/><references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Collins, J L.]]
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[[Category: Large Structures]]
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[[Category: Gampe, R T.]]
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[[Category: Collins JL]]
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[[Category: Kliewer, S A.]]
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[[Category: Gampe Jr RT]]
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[[Category: Lambert, M H.]]
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[[Category: Kliewer SA]]
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[[Category: McKee, D D.]]
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[[Category: Lambert MH]]
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[[Category: Montana, V G.]]
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[[Category: McKee DD]]
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[[Category: Moore, J T.]]
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[[Category: Montana VG]]
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[[Category: Moore, L B.]]
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[[Category: Moore JT]]
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[[Category: Oplinger, J A.]]
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[[Category: Moore LB]]
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[[Category: Willson, T M.]]
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[[Category: Oplinger JA]]
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[[Category: Xu, H E.]]
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[[Category: Willson TM]]
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[[Category: The 2 5 angstrom resolution crystal structure of the human pparalpha ligand binding domain bound with gw409544 and a coactivator peptide]]
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[[Category: Xu HE]]
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[[Category: Transcription]]
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Current revision

The 2.5 Angstrom resolution crystal structure of the human PPARalpha ligand binding domain bound with GW409544 and a co-activator peptide.

PDB ID 1k7l

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