This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.

3sp9

From Proteopedia

(Difference between revisions)

Jump to: navigation, search

Revision as of 02:36, 5 August 2016

Structural basis for iloprost as a dual PPARalpha/delta agonist

Structural highlights

3sp9 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:	3sp6
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

Iloprost is a prostacyclin analog that has been used to treat many vascular conditions. Peroxisome proliferator-activated receptors (PPARs) are ligand-regulated transcription factors with various important biological effects such as metabolic and cardiovascular physiology. Here, we report the crystal structures of the PPARalpha ligand-binding domain and PPARdelta ligand-binding domain bound to iloprost, thus providing unambiguous evidence for the direct interaction between iloprost and PPARs and a structural basis for the recognition of PPARalpha/delta by this prostacyclin analog. In addition to conserved contacts for all PPARalpha ligands, iloprost also initiates several specific interactions with PPARs using its unique structural groups. Structural and functional studies of receptor-ligand interactions reveal strong functional correlations of the iloprost-PPARalpha/delta interactions as well as the molecular basis of PPAR subtype selectivity toward iloprost ligand. As such, the structural mechanism may provide a more rational template for designing novel compounds targeting PPARs with more favorable pharmacologic impact based on existing iloprost drugs.

Structural basis for iloprost as a dual peroxisome proliferator-activated receptor alpha/delta agonist.,Jin L, Lin S, Rong H, Zheng S, Jin S, Wang R, Li Y J Biol Chem. 2011 Sep 9;286(36):31473-9. Epub 2011 Jul 20. PMID:21775429^[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
↑ Jin L, Lin S, Rong H, Zheng S, Jin S, Wang R, Li Y. Structural basis for iloprost as a dual peroxisome proliferator-activated receptor alpha/delta agonist. J Biol Chem. 2011 Sep 9;286(36):31473-9. Epub 2011 Jul 20. PMID:21775429 doi:10.1074/jbc.M111.266023

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3sp9"

@@ Line 1: / Line 1: @@
 ==Structural basis for iloprost as a dual PPARalpha/delta agonist==
 <StructureSection load='3sp9' size='340' side='right' caption='[[3sp9]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
@@ Line 6: / Line 7: @@
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3sp6|3sp6]]</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=3sp9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3sp9 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3sp9 RCSB], [http://www.ebi.ac.uk/pdbsum/3sp9 PDBsum]</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=3sp9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3sp9 OCA], [http://pdbe.org/3sp9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3sp9 RCSB], [http://www.ebi.ac.uk/pdbsum/3sp9 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3sp9 ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 18: / Line 19: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 3sp9" style="background-color:#fffaf0;"></div>
 ==See Also==

3sp9

From Proteopedia

Revision as of 02:36, 5 August 2016

Structural basis for iloprost as a dual PPARalpha/delta agonist

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox