PDBsum entry 2vsr

Receptor

PDB id: 2vsr

Contents

Protein chain

257 a.a. *

Ligands

9HO ×3

Waters ×119

* Residue conservation analysis

PDB id:

2vsr

Name:

Receptor

Title:

Hppargamma ligand binding domain in complex with 9-(s)-hode

Structure:

Peroxisome proliferator-activated receptor gamma. Chain: a, b. Fragment: ligand binding domain, residues 202-475. Synonym: ppar gamma, nuclear receptor subfamily 1 group c member 3. Engineered: yes. Other_details: 9-(s)-hode

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 511693. Expression_system_variant: rosetta.

Resolution:

2.05Å R-factor: 0.226 R-free: 0.266

Authors:

T.Itoh,L.Fairall,J.W.R.Schwabe

Key ref:

T.Itoh et al. (2008). Structural basis for the activation of PPARgamma by oxidized fatty acids. Nat Struct Biol, 15, 924-931. PubMed id: 19172745

Date:

29-Apr-08 Release date: 19-Aug-08

Protein chains

P37231  (PPARG_HUMAN) -  Peroxisome proliferator-activated receptor gamma from Homo sapiens

Seq: 505 a.a.

Struc: 257 a.a.

Nat Struct Biol 15:924-931 (2008)

PubMed id: 19172745

Structural basis for the activation of PPARgamma by oxidized fatty acids.

T.Itoh, L.Fairall, K.Amin, Y.Inaba, A.Szanto, B.L.Balint, L.Nagy, K.Yamamoto, J.W.Schwabe.

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.