2VV4

hPPARgamma Ligand binding domain in complex with 6-oxoOTE

2VV4 の概要

• エントリーDOI: 10.2210/pdb2vv4/pdb
• 関連するPDBエントリー: 1FM6 1FM9 1I7I 1K74 1KNU 1NYX 1PRG 1RDT 1WM0 1ZGY 2F4B 2FVJ 2G0G 2G0H 2PRG 2VSR 2VST 2VV0 2VV1 2VV2 2VV3 3PRG 4PRG
• 分子名称: PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR GAMMA, (8R,9Z,12Z)-8-hydroxy-6-oxooctadeca-9,12-dienoic acid, (8E,10S,12Z)-10-hydroxy-6-oxooctadeca-8,12-dienoic acid, ... (5 entities in total)
• 機能のキーワード: receptor, nuclear receptor, ligand binding domain, oxidised fatty acid, transcription factor
• 由来する生物種: HOMO SAPIENS (HUMAN); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 63533.92

構造登録者

Itoh, T.,Fairall, L.,Schwabe, J.W.R. (登録日: 2008-06-02, 公開日: 2008-08-19, 最終更新日: 2024-11-20)

主引用文献

Itoh, T.,Fairall, L.,Amin, K.,Inaba, Y.,Szanto, A.,Balint, B.L.,Nagy, L.,Yamamoto, K.,Schwabe, J.W.R.
Structural Basis for the Activation of Pparg by Oxidised Fatty Acids
Nat.Struct.Mol.Biol., 15:924-, 2008

PubMed Abstract: The nuclear receptor peroxisome proliferator-activated receptor-gamma (PPARgamma) has important roles in adipogenesis and immune response as well as roles in both lipid and carbohydrate metabolism. Although synthetic agonists for PPARgamma are widely used as insulin sensitizers, the identity of the natural ligand(s) for PPARgamma is still not clear. Suggested natural ligands include 15-deoxy-delta12,14-prostaglandin J2 and oxidized fatty acids such as 9-HODE and 13-HODE. Crystal structures of PPARgamma have revealed the mode of recognition for synthetic compounds. Here we report structures of PPARgamma bound to oxidized fatty acids that are likely to be natural ligands for this receptor. These structures reveal that the receptor can (i) simultaneously bind two fatty acids and (ii) couple covalently with conjugated oxo fatty acids. Thermal stability and gene expression analyses suggest that such covalent ligands are particularly effective activators of PPARgamma and thus may serve as potent and biologically relevant ligands.

PubMed: 19172745
DOI: 10.1038/NSMB.1474

実験手法

X-RAY DIFFRACTION (2.35 Å)