3sp9 | pdb_00003sp9

Structural basis for iloprost as a dual PPARalpha/delta agonist

spinqualitylabelsall models 3sp9, resolution 2.30Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D 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: IL2 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. 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Peroxisome proliferator-activated receptor 3D structures

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