5u3s: Difference between revisions

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 ==Human PPARdelta ligand-binding domain in complexed with specific agonist 3==
-<StructureSection load='5u3s' size='340' side='right' caption='[[5u3s]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
+<StructureSection load='5u3s' size='340' side='right'caption='[[5u3s]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
 == 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5U3S FirstGlance]. <br>
+<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>
+</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&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5u3q|5u3q]], [[5u3r|5u3r]], [[5u3t|5u3t]], [[5u3u|5u3u]], [[5u3v|5u3v]], [[5u3w|5u3w]], [[5u3x|5u3x]], [[5u3y|5u3y]], [[5u3z|5u3z]], [[5u40|5u40]], [[5u41|5u41]], [[5u42|5u42]], [[5u44|5u44]], [[5u45|5u45]], [[5u46|5u46]]</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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5u3s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5u3s OCA], [http://pdbe.org/5u3s PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5u3s RCSB], [http://www.ebi.ac.uk/pdbsum/5u3s PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5u3s ProSAT]</span></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=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>
 == 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>
+<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&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</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/>
 __TOC__
 </StructureSection>
-[[Category: Atkins, A R]]
+[[Category: Homo sapiens]]
-[[Category: Baiga, T J]]
+[[Category: Large Structures]]
-[[Category: Bowman, M E]]
+[[Category: Atkins AR]]
-[[Category: Clair, J J.La]]
+[[Category: Baiga TJ]]
-[[Category: Downes, M]]
+[[Category: Bowman ME]]
-[[Category: Evans, R M]]
+[[Category: Downes M]]
-[[Category: Noel, J P]]
+[[Category: Evans RM]]
-[[Category: Richard, S B]]
+[[Category: La Clair JJ]]
-[[Category: Stockley-Noel, T A]]
+[[Category: Noel JP]]
-[[Category: Wu, C C]]
+[[Category: Richard SB]]
-[[Category: Agonist]]
+[[Category: Stockley-Noel TA]]
-[[Category: Ligand-binding domain]]
+[[Category: Wu C-C]]
-[[Category: Ppardelta]]
-[[Category: Protein binding-activator complex]]