3SP9

Structural basis for iloprost as a dual PPARalpha/delta agonist

3SP9 の概要

• エントリーDOI: 10.2210/pdb3sp9/pdb
• 関連するPDBエントリー: 3SP6
• 分子名称: Peroxisome proliferator-activated receptor delta, (5E)-5-[(3aS,4R,5R,6aS)-5-hydroxy-4-[(1E,3S,4R)-3-hydroxy-4-methyloct-1-en-6-yn-1-yl]hexahydropentalen-2(1H)-ylidene]pentanoic acid (3 entities in total)
• 機能のキーワード: nuclear receptor lbd, nuclear receptor fold, ligand binding, gene transcription, drug binding, transcription
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Nucleus: Q03181
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 65179.78

構造登録者

Rong, H.,Li, Y. (登録日: 2011-07-01, 公開日: 2011-07-20, 最終更新日: 2024-02-28)

主引用文献

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., 286:31473-31479, 2011

PubMed Abstract: 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 PPARα ligand-binding domain and PPARδ 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 PPARα/δ by this prostacyclin analog. In addition to conserved contacts for all PPARα 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-PPARα/δ 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.

PubMed: 21775429
DOI: 10.1074/jbc.M111.266023

実験手法

X-RAY DIFFRACTION (2.3 Å)