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5u46

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Revision as of 10:21, 22 November 2017

Human PPARdelta ligand-binding domain in complexed with GW501516

Structural highlights

5u46 is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, , ,
Related:	5u3q, 5u3r, 5u3s, 5u3t, 5u3u, 5u3v, 5u3w, 5u3x, 5u3y, 5u3z, 5u40, 5u41, 5u42, 5u43, 5u44, 5u45
Gene:	PPARD, NR1C2, PPARB (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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 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^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Schmidt A, Endo N, Rutledge SJ, Vogel R, Shinar D, Rodan GA. Identification of a new member of the steroid hormone receptor superfamily that is activated by a peroxisome proliferator and fatty acids. Mol Endocrinol. 1992 Oct;6(10):1634-41. PMID:1333051 doi:http://dx.doi.org/10.1210/mend.6.10.1333051
↑ van der Veen JN, Kruit JK, Havinga R, Baller JF, Chimini G, Lestavel S, Staels B, Groot PH, Groen AK, Kuipers F. Reduced cholesterol absorption upon PPARdelta activation coincides with decreased intestinal expression of NPC1L1. J Lipid Res. 2005 Mar;46(3):526-34. Epub 2004 Dec 16. PMID:15604518 doi:http://dx.doi.org/10.1194/jlr.M400400-JLR200
↑ Wu CC, Baiga TJ, Downes M, La Clair JJ, Atkins AR, Richard SB, Fan W, Stockley-Noel TA, Bowman ME, Noel JP, Evans RM. Structural basis for specific ligation of the peroxisome proliferator-activated receptor delta. Proc Natl Acad Sci U S A. 2017 Mar 20. pii: 201621513. doi:, 10.1073/pnas.1621513114. PMID:28320959 doi:http://dx.doi.org/10.1073/pnas.1621513114

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5u46"

@@ Line 3: / Line 3: @@
 <StructureSection load='5u46' size='340' side='right' caption='[[5u46]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5u46]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5U46 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5U46 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5u46]] 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=5U46 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5U46 FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=7T1:{2-METHYL-4-[({4-METHYL-2-[4-(TRIFLUOROMETHYL)PHENYL]-1,3-THIAZOL-5-YL}METHYL)SULFANYL]PHENOXY}ACETIC+ACID'>7T1</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]], [[5u3x|5u3x]], [[5u3y|5u3y]], [[5u3z|5u3z]], [[5u40|5u40]], [[5u41|5u41]], [[5u42|5u42]], [[5u43|5u43]], [[5u44|5u44]], [[5u45|5u45]]</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=5u46 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5u46 OCA], [http://pdbe.org/5u46 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5u46 RCSB], [http://www.ebi.ac.uk/pdbsum/5u46 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5u46 ProSAT]</span></td></tr>
 </table>
@@ Line 23: / Line 24: @@
 __TOC__
 </StructureSection>
+[[Category: Human]]
 [[Category: Atkins, A R]]
 [[Category: Baiga, T J]]

5u46

From Proteopedia

Revision as of 10:21, 22 November 2017

Human PPARdelta ligand-binding domain in complexed with GW501516

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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