1prg

From Proteopedia

proteopedia linkproteopedia link

spinqualitylabelsall models 1prg, resolution 2.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

LIGAND BINDING DOMAIN OF THE HUMAN PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

Overview

The peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is a, ligand-dependent transcription factor that is important in adipocyte, differentiation and glucose homeostasis and which depends on interactions, with co-activators, including steroid receptor co-activating factor-1, (SRC-1). Here we present the X-ray crystal structure of the human, apo-PPAR-gamma ligand-binding domain (LBD), at 2.2 A resolution; this, structure reveals a large binding pocket, which may explain the diversity, of ligands for PPAR-gamma. We also describe the ternary complex containing, the PPAR-gamma LBD, the antidiabetic ligand rosiglitazone (BRL49653), and, 88 amino acids of human SRC-1 at 2.3 A resolution. Glutamate and lysine, residues that are highly conserved in LBDs of nuclear receptors form a, 'charge clamp' that contacts backbone atoms of the LXXLL helices of SRC-1., These results, together with the observation that two consecutive LXXLL, motifs of SRC-1 make identical contacts with both subunits of a PPAR-gamma, homodimer, suggest a general mechanism for the assembly of nuclear, receptors with co-activators.

Disease

Known diseases associated with this structure: Abdominal body fat distribution, modifier of OMIM:[601487], Diabetes mellitus, insulin-resistant, with acanthosis nigricans and hypertension OMIM:[601487], Glioblastoma, susceptibility to OMIM:[601487], Insulin resistance, severe, digenic OMIM:[601487], Lipodystrophy, familial partial OMIM:[601487], Obesity, resistance to OMIM:[601487], Obesity, severe OMIM:[601487]

About this Structure

1PRG is a Single protein structure of sequence from Homo sapiens. Known structural/functional Sites: and . Full crystallographic information is available from OCA.

Reference

Ligand binding and co-activator assembly of the peroxisome proliferator-activated receptor-gamma., Nolte RT, Wisely GB, Westin S, Cobb JE, Lambert MH, Kurokawa R, Rosenfeld MG, Willson TM, Glass CK, Milburn MV, Nature. 1998 Sep 10;395(6698):137-43. PMID:9744270

Page seeded by OCA on Sun Feb 3 10:00:01 2008