5hyk: Difference between revisions
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==Crystal structure of the complex PPARalpha/AL26-29== | ==Crystal structure of the complex PPARalpha/AL26-29== | ||
<StructureSection load='5hyk' size='340' side='right' caption='[[5hyk]], [[Resolution|resolution]] 1.83Å' scene=''> | <StructureSection load='5hyk' size='340' side='right'caption='[[5hyk]], [[Resolution|resolution]] 1.83Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5hyk]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5HYK OCA]. For a <b>guided tour on the structure components</b> use [ | <table><tr><td colspan='2'>[[5hyk]] is a 1 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=5HYK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5HYK FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=65W:2-METHYL-2-[4-(NAPHTHALEN-1-YL)PHENOXY]PROPANOIC+ACID'>65W</scene></td></tr> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.83Å</td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=65W:2-METHYL-2-[4-(NAPHTHALEN-1-YL)PHENOXY]PROPANOIC+ACID'>65W</scene></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5hyk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5hyk OCA], [https://pdbe.org/5hyk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5hyk RCSB], [https://www.ebi.ac.uk/pdbsum/5hyk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5hyk ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Function == | == Function == | ||
[ | [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> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
| Line 18: | Line 19: | ||
</div> | </div> | ||
<div class="pdbe-citations 5hyk" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 5hyk" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Peroxisome proliferator-activated receptor 3D structures|Peroxisome proliferator-activated receptor 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Capelli D]] | ||
[[Category: | [[Category: Laghezza A]] | ||
[[Category: | [[Category: Lavecchia A]] | ||
[[Category: | [[Category: Loiodice F]] | ||
[[Category: | [[Category: Montanari R]] | ||
[[Category: | [[Category: Pochetti G]] | ||
Latest revision as of 14:00, 16 August 2023
Crystal structure of the complex PPARalpha/AL26-29Crystal structure of the complex PPARalpha/AL26-29
Structural highlights
FunctionPPARA_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.[1] [2] [3] [4] Publication Abstract from PubMedThe peroxisome proliferator-activated receptors (PPARs) are nuclear receptors involved in the regulation of the metabolic homeostasis and therefore represent valuable therapeutic targets for the treatment of metabolic diseases. The development of more balanced drugs interacting with PPARs, devoid of the side-effects showed by the currently marketed PPARgamma full agonists, is considered the major challenge for the pharmaceutical companies. Here we present a structure-based virtual screening approach that let us identify a novel PPAR pan-agonist with a very attractive activity profile and its crystal structure in the complex with PPARalpha and PPARgamma, respectively. In PPARalpha this ligand occupies a new pocket whose filling is allowed by the ligand-induced switching of the F273 side chain from a closed to an open conformation. The comparison between this pocket and the corresponding cavity in PPARgamma provides a rationale for the different activation of the ligand towards PPARalpha and PPARgamma, suggesting a novel basis for ligand design. Structural basis for PPAR partial or full activation revealed by a novel ligand binding mode.,Capelli D, Cerchia C, Montanari R, Loiodice F, Tortorella P, Laghezza A, Cervoni L, Pochetti G, Lavecchia A Sci Rep. 2016 Oct 6;6:34792. doi: 10.1038/srep34792. PMID:27708429[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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