5u44: Difference between revisions

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'''Unreleased structure'''


The entry 5u44 is ON HOLD until Paper Publication
==Human PPARdelta ligand-binding domain in complexed with specific agonist 13==
<StructureSection load='5u44' size='340' side='right' caption='[[5u44]], [[Resolution|resolution]] 2.15&Aring;' scene=''>
== 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>
</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='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>
== 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.


Authors: Wu, C.-C., Baiga, T.J., Downes, M. , La Clair, J.J., Atkins, A.R., Richard, S.B., Stockley-Noel, T.A., Bowman, M.E., Evans, R.M., Noel, J.P.
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>


Description: Human PPARdelta ligand-binding domain in complexed with specific agonist 13
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
[[Category: Unreleased Structures]]
</div>
[[Category: Wu, C.-C]]
<div class="pdbe-citations 5u44" style="background-color:#fffaf0;"></div>
[[Category: Noel, J.P]]
== References ==
[[Category: Richard, S.B]]
<references/>
[[Category: Atkins, A.R]]
__TOC__
[[Category: Baiga, T.J]]
</StructureSection>
[[Category: Bowman, M.E]]
[[Category: Atkins, A R]]
[[Category: Evans, R.M]]
[[Category: Baiga, T J]]
[[Category: Downes, M. , La Clair, J.J]]
[[Category: Bowman, M E]]
[[Category: Stockley-Noel, T.A]]
[[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]]

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