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7c6q

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(New page: '''Unreleased structure''' The entry 7c6q is ON HOLD Authors: Tian, S.Y., Wang, R., Zheng, W.L., Li, Y. Description: Novel natural PPARalpha agonist with a unique binding mode [[Catego...)
Current revision (15:57, 29 November 2023) (edit) (undo)
 
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'''Unreleased structure'''
 
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The entry 7c6q is ON HOLD
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==Novel natural PPARalpha agonist with a unique binding mode==
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<StructureSection load='7c6q' size='340' side='right'caption='[[7c6q]], [[Resolution|resolution]] 2.76&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[7c6q]] is a 2 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=7C6Q OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7C6Q FirstGlance]. <br>
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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]] 2.76&#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=SAU:13-METHYL[1,3]BENZODIOXOLO[5,6-C][1,3]DIOXOLO[4,5-I]PHENANTHRIDIN-13-IUM'>SAU</scene></td></tr>
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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=7c6q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7c6q OCA], [https://pdbe.org/7c6q PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7c6q RCSB], [https://www.ebi.ac.uk/pdbsum/7c6q PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7c6q ProSAT]</span></td></tr>
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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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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Peroxisome proliferator-activated receptors (PPARs) play crucial roles in glucose and lipid metabolism and inflammation. Sanguinarine is a natural product that is isolated from Sanguinaria Canadensis, a potential therapeutic agent for intervention in chronic diseases. In this study, biochemical and cell-based promoter-reporter gene assays revealed that sanguinarine activated both PPARalpha and PPARgamma, and enhanced their transcriptional activity; thus, sanguinarine was identified as a dual agonist of PPARalpha/gamma. Similar to fenofibrate, sanguinarine upregulates the expression of PPARalpha-target genes in hepatocytes. Sanguinarine also modulates the expression of key PPARgamma-target genes and promotes adipocyte differentiation, but with a lower adipogenic activity compared with rosiglitazone. We report the crystal structure of sanguinarine bound to PPARalpha, which reveals a unique ligand-binding mode of sanguinarine, dissimilar to the classic Y-shaped binding pocket, which may represent a new pharmacophore that can be optimized for selectively targeting PPARalpha. Further structural and functional studies uncover the molecular basis for the selectivity of sanguinarine toward PPARalpha/gamma among all three PPARs. In summary, our study identifies a PPARalpha/gamma dual agonist with a unique ligand-binding mode, and provides a promising and viable novel template for the design of dual-targeting PPARs ligands.
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Authors: Tian, S.Y., Wang, R., Zheng, W.L., Li, Y.
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Structural Basis for PPARs Activation by The Dual PPARalpha/gamma Agonist Sanguinarine: A Unique Mode of Ligand Recognition.,Tian S, Wang R, Chen S, He J, Zheng W, Li Y Molecules. 2021 Oct 3;26(19):6012. doi: 10.3390/molecules26196012. PMID:34641558<ref>PMID:34641558</ref>
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Description: Novel natural PPARalpha agonist with a unique binding mode
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[Category: Unreleased Structures]]
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</div>
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[[Category: Zheng, W.L]]
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<div class="pdbe-citations 7c6q" style="background-color:#fffaf0;"></div>
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[[Category: Li, Y]]
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[[Category: Wang, R]]
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==See Also==
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[[Category: Tian, S.Y]]
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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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<references/>
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__TOC__
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</StructureSection>
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[[Category: Homo sapiens]]
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[[Category: Large Structures]]
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[[Category: Li Y]]
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[[Category: Tian SY]]
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[[Category: Wang R]]
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[[Category: Zheng WL]]

Current revision

Novel natural PPARalpha agonist with a unique binding mode

PDB ID 7c6q

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