5u44: Difference between revisions
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<StructureSection load='5u44' size='340' side='right' caption='[[5u44]], [[Resolution|resolution]] 2.15Å' scene=''> | <StructureSection load='5u44' size='340' side='right' caption='[[5u44]], [[Resolution|resolution]] 2.15Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5u44]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5U44 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5U44 FirstGlance]. <br> | <table><tr><td colspan='2'>[[5u44]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5U44 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5U44 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=7SV:6-(2-{[CYCLOPROPYL(2-FLUORO[1,1-BIPHENYL]-4-CARBONYL)AMINO]METHYL}PHENOXY)HEXANOIC+ACID'>7SV</scene>, <scene name='pdbligand=B7G:HEPTYL-BETA-D-GLUCOPYRANOSIDE'>B7G</scene>, <scene name='pdbligand=PGO:S-1,2-PROPANEDIOL'>PGO</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=7SV:6-(2-{[CYCLOPROPYL(2-FLUORO[1,1-BIPHENYL]-4-CARBONYL)AMINO]METHYL}PHENOXY)HEXANOIC+ACID'>7SV</scene>, <scene name='pdbligand=B7G:HEPTYL-BETA-D-GLUCOPYRANOSIDE'>B7G</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]], [[5u3x|5u3x]], [[5u3y|5u3y]], [[5u3z|5u3z]], [[5u40|5u40]], [[5u41|5u41]], [[5u42|5u42]], [[5u43|5u43]], [[5u45|5u45]], [[5u46|5u46]]</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]], [[5u3x|5u3x]], [[5u3y|5u3y]], [[5u3z|5u3z]], [[5u40|5u40]], [[5u41|5u41]], [[5u42|5u42]], [[5u43|5u43]], [[5u45|5u45]], [[5u46|5u46]]</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 HUMAN])</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=5u44 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5u44 OCA], [http://pdbe.org/5u44 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5u44 RCSB], [http://www.ebi.ac.uk/pdbsum/5u44 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5u44 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=5u44 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5u44 OCA], [http://pdbe.org/5u44 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5u44 RCSB], [http://www.ebi.ac.uk/pdbsum/5u44 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5u44 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Human]] | |||
[[Category: Atkins, A R]] | [[Category: Atkins, A R]] | ||
[[Category: Baiga, T J]] | [[Category: Baiga, T J]] | ||
Revision as of 13:20, 22 November 2017
Human PPARdelta ligand-binding domain in complexed with specific agonist 13Human PPARdelta ligand-binding domain in complexed with specific agonist 13
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] 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. References
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