6l37

<table><tr><td colspan='2'>[[6l37]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6L37 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6L37 FirstGlance]. <br>

</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=C5F:2-{4-[(1S)-2,2-dichlorocyclopropyl]phenoxy}-2-methylpropanoic+acid'>C5F</scene>, <scene name='pdbligand=GW9:2-CHLORO-5-NITRO-N-PHENYLBENZAMIDE'>GW9</scene></td></tr>

<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6l37 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6l37 OCA], [http://pdbe.org/6l37 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6l37 RCSB], [http://www.ebi.ac.uk/pdbsum/6l37 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6l37 ProSAT]</span></td></tr>

== Function ==

[[http://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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== Publication Abstract from PubMed ==

Most triacylglycerol-lowering fibrates have been developed in the 1960s-1980s before their molecular target, peroxisome proliferator-activated receptor alpha (PPARalpha), was identified. Twenty-one ligand-bound PPARalpha structures have been deposited in the Protein Data Bank since 2001; however, binding modes of fibrates and physiological ligands remain unknown. Here we show thirty-four X-ray crystallographic structures of the PPARalpha ligand-binding domain, which are composed of a "Center" and four "Arm" regions, in complexes with five endogenous fatty acids, six fibrates in clinical use, and six synthetic PPARalpha agonists. High-resolution structural analyses, in combination with coactivator recruitment and thermostability assays, demonstrate that stearic and palmitic acids are presumably physiological ligands; coordination to Arm III is important for high PPARalpha potency/selectivity of pemafibrate and GW7647; and agonistic activities of four fibrates are enhanced by the partial agonist GW9662. These results renew our understanding of PPARalpha ligand recognition and contribute to the molecular design of next-generation PPAR-targeted drugs.

 

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== References ==

[[Category: Human]]

[[Category: Honda, A]]

[[Category: Ishii, I]]

[[Category: Ishikawa, R]]

[[Category: Kamata, S]]

[[Category: Oyama, T]]

[[Category: Saito, K]]

[[Category: Transcription]]