5u3s: Difference between revisions
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==Human PPARdelta ligand-binding domain in complexed with specific agonist 3== | ==Human PPARdelta ligand-binding domain in complexed with specific agonist 3== | ||
<StructureSection load='5u3s' size='340' side='right' caption='[[5u3s]], [[Resolution|resolution]] 2.00Å' scene=''> | <StructureSection load='5u3s' size='340' side='right'caption='[[5u3s]], [[Resolution|resolution]] 2.00Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5u3s]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5U3S OCA]. For a <b>guided tour on the structure components</b> use [ | <table><tr><td colspan='2'>[[5u3s]] 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=5U3S OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5U3S FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=7V4:6-[2-({[4-(FURAN-3-YL)BENZENE-1-CARBONYL](PROPAN-2-YL)AMINO}METHYL)PHENOXY]HEXANOIC+ACID'>7V4</scene>, <scene name='pdbligand=B7G:HEPTYL-BETA-D-GLUCOPYRANOSIDE'>B7G</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PGO:S-1,2-PROPANEDIOL'>PGO</scene> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=7V4:6-[2-({[4-(FURAN-3-YL)BENZENE-1-CARBONYL](PROPAN-2-YL)AMINO}METHYL)PHENOXY]HEXANOIC+ACID'>7V4</scene>, <scene name='pdbligand=B7G:HEPTYL-BETA-D-GLUCOPYRANOSIDE'>B7G</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PGO:S-1,2-PROPANEDIOL'>PGO</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5u3s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5u3s OCA], [https://pdbe.org/5u3s PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5u3s RCSB], [https://www.ebi.ac.uk/pdbsum/5u3s PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5u3s ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == 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> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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</div> | </div> | ||
<div class="pdbe-citations 5u3s" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 5u3s" 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: Atkins AR]] | ||
[[Category: | [[Category: Baiga TJ]] | ||
[[Category: | [[Category: Bowman ME]] | ||
[[Category: | [[Category: Downes M]] | ||
[[Category: | [[Category: Evans RM]] | ||
[[Category: | [[Category: La Clair JJ]] | ||
[[Category: | [[Category: Noel JP]] | ||
[[Category: | [[Category: Richard SB]] | ||
[[Category: | [[Category: Stockley-Noel TA]] | ||
[[Category: Wu C-C]] | |||
[[Category: | |||
Latest revision as of 16:19, 4 October 2023
Human PPARdelta ligand-binding domain in complexed with specific agonist 3Human PPARdelta ligand-binding domain in complexed with specific agonist 3
Structural highlights
FunctionPPARD_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] Publication Abstract from PubMedThe peroxisome proliferator-activated receptor (PPAR) family comprises three subtypes: PPARalpha, PPARgamma, and PPARdelta. PPARdelta transcriptionally modulates lipid metabolism and the control of energy homeostasis; therefore, PPARdelta agonists are promising agents for treating a variety of metabolic disorders. In the present study, we develop a panel of rationally designed PPARdelta agonists. The modular motif affords efficient syntheses using building blocks optimized for interactions with subtype-specific residues in the PPARdelta ligand-binding domain (LBD). A combination of atomic-resolution protein X-ray crystallographic structures, ligand-dependent LBD stabilization assays, and cell-based transactivation measurements delineate structure-activity relationships (SARs) for PPARdelta-selective targeting and structural modulation. We identify key ligand-induced conformational transitions of a conserved tryptophan side chain in the LBD that trigger reorganization of the H2'-H3 surface segment of PPARdelta. The subtype-specific conservation of H2'-H3 sequences suggests that this architectural remodeling constitutes a previously unrecognized conformational switch accompanying ligand-dependent PPARdelta transcriptional regulation. Structural basis for specific ligation of the peroxisome proliferator-activated receptor delta.,Wu CC, Baiga TJ, Downes M, La Clair JJ, Atkins AR, Richard SB, Fan W, Stockley-Noel TA, Bowman ME, Noel JP, Evans RM Proc Natl Acad Sci U S A. 2017 Mar 20. pii: 201621513. doi:, 10.1073/pnas.1621513114. PMID:28320959[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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