1PQ9

HUMAN LXR BETA HORMONE RECEPTOR COMPLEXED WITH T0901317 COMPLEX

Summary for 1PQ9

• Entry DOI: 10.2210/pdb1pq9/pdb
• Related: 1pq6 1pqc
• Descriptor: Oxysterols receptor LXR-beta, benzenesulfonic acid, 1,1,1,3,3,3-HEXAFLUORO-2-{4-[(2,2,2-TRIFLUOROETHYL)AMINO]PHENYL}PROPAN-2-OL, ... (4 entities in total)
• Functional Keywords: lxrb+t0901317 split, transcription regulation
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus (Potential): P55055
• Total number of polymer chains: 4
• Total formula weight: 118226.52

Authors

Farnegardh, M.,Bonn, T.,Sun, S.,Ljunggren, J.,Ahola, H.,Wilhelmsson, A.,Gustafsson, J.-A.,Carlquist, M. (deposition date: 2003-06-18, release date: 2003-09-09, Last modification date: 2024-04-03)

Primary citation

Farnegardh, M.,Bonn, T.,Sun, S.,Ljunggren, J.,Ahola, H.,Wilhelmsson, A.,Gustafsson, J.-A.,Carlquist, M.
The three-dimensional structure of the liver X receptor beta reveals a flexible ligand-binding pocket that can accommodate fundamentally different ligands.
J.Biol.Chem., 278:38821-38828, 2003

PubMed Abstract: The structures of the liver X receptor LXRbeta (NR1H2) have been determined in complexes with two synthetic ligands, T0901317 and GW3965, to 2.1 and 2.4 A, respectively. Together with its isoform LXRalpha (NR1H3) it regulates target genes involved in metabolism and transport of cholesterol and fatty acids. The two LXRbeta structures reveal a flexible ligand-binding pocket that can adjust to accommodate fundamentally different ligands. The ligand-binding pocket is hydrophobic but with polar or charged residues at the two ends of the cavity. T0901317 takes advantage of this by binding to His-435 close to H12 while GW3965 orients itself with its charged group in the opposite direction. Both ligands induce a fixed "agonist conformation" of helix H12 (also called the AF-2 domain), resulting in a transcriptionally active receptor.

PubMed: 12819202
DOI: 10.1074/jbc.M304842200

Experimental method

X-RAY DIFFRACTION (2.1 Å)