2q5g: Difference between revisions

Latest revision as of 11:21, 30 August 2023

Ligand binding domain of PPAR delta receptor in complex with a partial agonist

Structural highlights

2q5g is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.7Å
Ligands:	1FA
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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

Structure based ligand design was used in order to design a partial agonist for the PPARdelta receptor. The maximum activation in the transactivation assay was reduced from 87% to 39%. The crystal structure of the ligand binding domain of the PPARdelta receptor in complex with compound 2 was determined in order to understand the structural changes which gave rise to the decrease in maximum activation.

Design of a partial PPARdelta agonist.,Pettersson I, Ebdrup S, Havranek M, Pihera P, Korinek M, Mogensen JP, Jeppesen CB, Johansson E, Sauerberg P Bioorg Med Chem Lett. 2007 Aug 15;17(16):4625-9. Epub 2007 May 27. PMID:17560785^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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:https://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:https://dx.doi.org/10.1194/jlr.M400400-JLR200
↑ Pettersson I, Ebdrup S, Havranek M, Pihera P, Korinek M, Mogensen JP, Jeppesen CB, Johansson E, Sauerberg P. Design of a partial PPARdelta agonist. Bioorg Med Chem Lett. 2007 Aug 15;17(16):4625-9. Epub 2007 May 27. PMID:17560785 doi:10.1016/j.bmcl.2007.05.079

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OCA

[1] 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:https://dx.doi.org/10.1210/mend.6.10.1333051

[2] 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:https://dx.doi.org/10.1194/jlr.M400400-JLR200

[3] Pettersson I, Ebdrup S, Havranek M, Pihera P, Korinek M, Mogensen JP, Jeppesen CB, Johansson E, Sauerberg P. Design of a partial PPARdelta agonist. Bioorg Med Chem Lett. 2007 Aug 15;17(16):4625-9. Epub 2007 May 27. PMID:17560785 doi:10.1016/j.bmcl.2007.05.079

[1]

[2]

[3]

@@ Line 4: / Line 4: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[2q5g]] 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=2Q5G OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2Q5G FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1FA:[(7-{[2-(3-MORPHOLIN-4-YLPROP-1-YN-1-YL)-6-{[4-(TRIFLUOROMETHYL)PHENYL]ETHYNYL}PYRIDIN-4-YL]THIO}-2,3-DIHYDRO-1H-INDEN-4-YL)OXY]ACETIC+ACID'>1FA</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]] 2.7&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2gwx|2gwx]]</div></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1FA:[(7-{[2-(3-MORPHOLIN-4-YLPROP-1-YN-1-YL)-6-{[4-(TRIFLUOROMETHYL)PHENYL]ETHYNYL}PYRIDIN-4-YL]THIO}-2,3-DIHYDRO-1H-INDEN-4-YL)OXY]ACETIC+ACID'>1FA</scene></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PPARD, NR1C2, PPARB ([https://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=2q5g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2q5g OCA], [https://pdbe.org/2q5g PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2q5g RCSB], [https://www.ebi.ac.uk/pdbsum/2q5g PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2q5g ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[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>
+[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 ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 39: / Line 38: @@
 [[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Hoffman, I]]
+[[Category: Hoffman I]]
-[[Category: Hunter, M J]]
+[[Category: Hunter MJ]]
-[[Category: Johansson, E]]
+[[Category: Johansson E]]
-[[Category: Nix, J]]
+[[Category: Nix J]]
-[[Category: Pettersson, I]]
+[[Category: Pettersson I]]
-[[Category: Sauerberg, P]]
+[[Category: Sauerberg P]]
-[[Category: Tari, L W]]
+[[Category: Tari LW]]
-[[Category: Ppar delta]]
-[[Category: Transcription]]

2q5g: Difference between revisions

Latest revision as of 11:21, 30 August 2023

Ligand binding domain of PPAR delta receptor in complex with a partial agonist

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

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Proteopedia Page Contributors and Editors (what is this?)

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