1UPV

Crystal structure of the human Liver X receptor beta ligand binding domain in complex with a synthetic agonist

1UPV の概要

• エントリーDOI: 10.2210/pdb1upv/pdb
• 関連するPDBエントリー: 1P8D 1PQ6 1PQ9 1PQC 1UPW
• 分子名称: OXYSTEROLS RECEPTOR LXR-BETA, N-(2,2,2-TRIFLUOROETHYL)-N-{4-[2,2,2-TRIFLUORO-1-HYDROXY-1-(TRIFLUOROMETHYL)ETHYL]PHENYL}BENZENESULFONAMIDE (3 entities in total)
• 機能のキーワード: receptor, nuclear hormone receptor, ligand binding domain, liver x receptor, transcription factor
• 由来する生物種: HOMO SAPIENS (HUMAN)
• 細胞内の位置: Nucleus : P55055
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 29897.95

構造登録者

Hoerer, S.,Schmid, A.,Heckel, A.,Budzinski, R.M.,Nar, H. (登録日: 2003-10-13, 公開日: 2004-10-20, 最終更新日: 2023-12-13)

主引用文献

Hoerer, S.,Schmid, A.,Heckel, A.,Budzinski, R.M.,Nar, H.
Crystal Structure of the Human Liver X Receptor Beta Ligand-Binding Domain in Complex with a Synthetic Agonist
J.Mol.Biol., 334:853-, 2003

PubMed Abstract: LXRbeta belongs to the nuclear hormone receptor superfamily of ligand-activated transcription factors. Its natural ligands are supposed to be oxidised derivatives of cholesterol. Stimulation of LXRbeta by agonists activates a number of genes that are involved in the regulation of lipid metabolism and cholesterol efflux from cells. Therefore, LXRbeta may represent a novel therapeutic target for the treatment of dyslipidemia and atherosclerosis.Here, we report the X-ray crystal structure of the LXRbeta ligand-binding domain in complex with a synthetic agonist, T-0901317. This compound occupies the ligand-binding pocket of the receptor, forms numerous lipophilic contacts with the protein and one crucial hydrogen bond to His435 and stabilises the agonist conformation of the receptor ligand-binding domain. The recruitment of the AF2-region of the protein is not achieved via direct polar interactions of the ligand with protein side-chains of this helical segment, but rather via few hydrophobic contacts and probably more importantly via indirect effects involving the pre-orientation of side-chains that surround the ligand-binding pocket and form the interface to the AF2-helix. On the basis of these results we propose a binding mode and a mechanism of action for the putative natural ligands, oxidised derivatives of cholesterol.

PubMed: 14643652
DOI: 10.1016/J.JMB.2003.10.033

実験手法

X-RAY DIFFRACTION (2.1 Å)