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| | ==PPARdelta complexed with an anthranilic acid partial agonist== | | ==PPARdelta complexed with an anthranilic acid partial agonist== |
| - | <StructureSection load='3dy6' size='340' side='right' caption='[[3dy6]], [[Resolution|resolution]] 2.90Å' scene=''> | + | <StructureSection load='3dy6' size='340' side='right'caption='[[3dy6]], [[Resolution|resolution]] 2.90Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3dy6]] is a 2 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=3DY6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3DY6 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3dy6]] 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=3DY6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3DY6 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DY6:2-({[3-(3,4-DIHYDROISOQUINOLIN-2(1H)-YLSULFONYL)PHENYL]CARBONYL}AMINO)BENZOIC+ACID'>DY6</scene>, <scene name='pdbligand=IOD:IODIDE+ION'>IOD</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]] 2.9Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1gwx|1gwx]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DY6:2-({[3-(3,4-DIHYDROISOQUINOLIN-2(1H)-YLSULFONYL)PHENYL]CARBONYL}AMINO)BENZOIC+ACID'>DY6</scene>, <scene name='pdbligand=IOD:IODIDE+ION'>IOD</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PPARD, NR1C2, PPARB ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</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=3dy6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3dy6 OCA], [https://pdbe.org/3dy6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3dy6 RCSB], [https://www.ebi.ac.uk/pdbsum/3dy6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3dy6 ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3dy6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3dy6 OCA], [http://pdbe.org/3dy6 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3dy6 RCSB], [http://www.ebi.ac.uk/pdbsum/3dy6 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3dy6 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/PPARD_HUMAN PPARD_HUMAN]] Ligand-activated transcription factor. Receptor that binds peroxisome proliferators such as hypolipidemic drugs and fatty acids. Has a preference for poly-unsaturated fatty acids, such as gamma-linoleic acid and eicosapentanoic acid. Once activated by a ligand, the receptor binds to promoter elements of target genes. Regulates the peroxisomal beta-oxidation pathway of fatty acids. Functions as transcription activator for the acyl-CoA oxidase gene. Decreases expression of NPC1L1 once activated by a ligand.<ref>PMID:1333051</ref> <ref>PMID:15604518</ref> | + | [https://www.uniprot.org/uniprot/PPARD_HUMAN PPARD_HUMAN] Ligand-activated transcription factor. Receptor that binds peroxisome proliferators such as hypolipidemic drugs and fatty acids. Has a preference for poly-unsaturated fatty acids, such as gamma-linoleic acid and eicosapentanoic acid. Once activated by a ligand, the receptor binds to promoter elements of target genes. Regulates the peroxisomal beta-oxidation pathway of fatty acids. Functions as transcription activator for the acyl-CoA oxidase gene. Decreases expression of NPC1L1 once activated by a ligand.<ref>PMID:1333051</ref> <ref>PMID:15604518</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | ==See Also== | | ==See Also== |
| - | *[[Peroxisome Proliferator-Activated Receptors|Peroxisome Proliferator-Activated Receptors]] | + | *[[Peroxisome proliferator-activated receptor 3D structures|Peroxisome proliferator-activated receptor 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| - | [[Category: Lambert, M L]] | + | [[Category: Large Structures]] |
| - | [[Category: Shearer, B G]] | + | [[Category: Lambert ML]] |
| - | [[Category: Wilson, T M]] | + | [[Category: Shearer BG]] |
| - | [[Category: Xu, R]] | + | [[Category: Wilson TM]] |
| - | [[Category: Activator]] | + | [[Category: Xu R]] |
| - | [[Category: Dna-binding]]
| + | |
| - | [[Category: Metal-binding]]
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| - | [[Category: Nucleus]]
| + | |
| - | [[Category: Nulear receptor]]
| + | |
| - | [[Category: Ppar]]
| + | |
| - | [[Category: Transcription]]
| + | |
| - | [[Category: Transcription regulation]]
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| - | [[Category: Zinc-finger]]
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| Structural highlights
Function
PPARD_HUMAN Ligand-activated transcription factor. Receptor that binds peroxisome proliferators such as hypolipidemic drugs and fatty acids. Has a preference for poly-unsaturated fatty acids, such as gamma-linoleic acid and eicosapentanoic acid. Once activated by a ligand, the receptor binds to promoter elements of target genes. Regulates the peroxisomal beta-oxidation pathway of fatty acids. Functions as transcription activator for the acyl-CoA oxidase gene. Decreases expression of NPC1L1 once activated by a ligand.[1] [2]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Anthranilic acid GW9371 was identified as a novel class of PPARdelta partial agonist through high-throughput screening. The design and synthesis of SAR analogues is described. GSK1115 and GSK7227 show potent partial agonism of the PPARdelta target genes CPT1a and PDK4 in skeletal muscle cells.
Discovery of a novel class of PPARdelta partial agonists.,Shearer BG, Patel HS, Billin AN, Way JM, Winegar DA, Lambert MH, Xu RX, Leesnitzer LM, Merrihew RV, Huet S, Willson TM Bioorg Med Chem Lett. 2008 Sep 15;18(18):5018-22. Epub 2008 Aug 9. PMID:18722772[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Schmidt A, Endo N, Rutledge SJ, Vogel R, Shinar D, Rodan GA. Identification of a new member of the steroid hormone receptor superfamily that is activated by a peroxisome proliferator and fatty acids. Mol Endocrinol. 1992 Oct;6(10):1634-41. PMID:1333051 doi:http://dx.doi.org/10.1210/mend.6.10.1333051
- ↑ van der Veen JN, Kruit JK, Havinga R, Baller JF, Chimini G, Lestavel S, Staels B, Groot PH, Groen AK, Kuipers F. Reduced cholesterol absorption upon PPARdelta activation coincides with decreased intestinal expression of NPC1L1. J Lipid Res. 2005 Mar;46(3):526-34. Epub 2004 Dec 16. PMID:15604518 doi:http://dx.doi.org/10.1194/jlr.M400400-JLR200
- ↑ Shearer BG, Patel HS, Billin AN, Way JM, Winegar DA, Lambert MH, Xu RX, Leesnitzer LM, Merrihew RV, Huet S, Willson TM. Discovery of a novel class of PPARdelta partial agonists. Bioorg Med Chem Lett. 2008 Sep 15;18(18):5018-22. Epub 2008 Aug 9. PMID:18722772 doi:10.1016/j.bmcl.2008.08.011
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