2VV2

hPPARgamma Ligand binding domain in complex with 5-HEPA

Summary for 2VV2

• Entry DOI: 10.2210/pdb2vv2/pdb
• Related: 1FM6 1FM9 1I7I 1K74 1KNU 1NYX 1PRG 1RDT 1WM0 1ZGY 2F4B 2FVJ 2G0G 2G0H 2PRG 2VSR 2VST 2VV0 2VV1 2VV3 2VV4 3PRG 4PRG
• Descriptor: PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR GAMMA, (5R,6E,8Z,11Z,14Z,17Z)-5-hydroxyicosa-6,8,11,14,17-pentaenoic acid (3 entities in total)
• Functional Keywords: transcription regulation, alternative splicing, ligand binding domain, nuclear receptor, diabetes mellitus, zinc-finger, dna-binding, polymorphism, transcription, zinc, obesity, nucleus, receptor, activator, oxidised fatty acid, transcription factor, metal-binding, phosphoprotein, disease mutation
• Biological source: HOMO SAPIENS (HUMAN)
• Total number of polymer chains: 2
• Total formula weight: 63854.39

Authors

Itoh, T.,Fairall, L.,Schwabe, J.W.R. (deposition date: 2008-06-02, release date: 2008-08-19, Last modification date: 2023-12-13)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.75 Å)