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5u3x
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | + | ==Human PPARdelta ligand-binding domain in complexed with specific agonist 8== | |
| + | <StructureSection load='5u3x' size='340' side='right' caption='[[5u3x]], [[Resolution|resolution]] 2.10Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[5u3x]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5U3X OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5U3X FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=7U4:6-[2-({CYCLOPROPYL[4-(PYRIDIN-3-YL)BENZENE-1-CARBONYL]AMINO}METHYL)PHENOXY]HEXANOIC+ACID'>7U4</scene>, <scene name='pdbligand=B7G:HEPTYL-BETA-D-GLUCOPYRANOSIDE'>B7G</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PGO:S-1,2-PROPANEDIOL'>PGO</scene></td></tr> | ||
| + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5u3q|5u3q]], [[5u3r|5u3r]], [[5u3s|5u3s]], [[5u3t|5u3t]], [[5u3u|5u3u]], [[5u3v|5u3v]], [[5u3w|5u3w]], [[5u3y|5u3y]], [[5u3z|5u3z]], [[5u40|5u40]], [[5u41|5u41]], [[5u42|5u42]], [[5u44|5u44]], [[5u45|5u45]], [[5u46|5u46]]</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=5u3x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5u3x OCA], [http://pdbe.org/5u3x PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5u3x RCSB], [http://www.ebi.ac.uk/pdbsum/5u3x PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5u3x ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == 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> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The 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<ref>PMID:28320959</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: | + | <div class="pdbe-citations 5u3x" style="background-color:#fffaf0;"></div> |
| - | [[Category: Noel, J | + | == References == |
| - | [[Category: Richard, S | + | <references/> |
| - | [[Category: | + | __TOC__ |
| - | [[Category: | + | </StructureSection> |
| - | [[Category: | + | [[Category: Atkins, A R]] |
| - | [[Category: | + | [[Category: Baiga, T J]] |
| - | [[Category: | + | [[Category: Bowman, M E]] |
| - | [[Category: | + | [[Category: Clair, J J.La]] |
| + | [[Category: Downes, M]] | ||
| + | [[Category: Evans, R M]] | ||
| + | [[Category: Noel, J P]] | ||
| + | [[Category: Richard, S B]] | ||
| + | [[Category: Stockley-Noel, T A]] | ||
| + | [[Category: Wu, C C]] | ||
| + | [[Category: Agonist]] | ||
| + | [[Category: Ligand-binding domain]] | ||
| + | [[Category: Ppardelta]] | ||
| + | [[Category: Protein binding-activator complex]] | ||
Revision as of 07:03, 29 March 2017
Human PPARdelta ligand-binding domain in complexed with specific agonist 8
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