3IPQ

X-ray structure of GW3965 synthetic agonist bound to the LXR-alpha

3IPQ の概要

• エントリーDOI: 10.2210/pdb3ipq/pdb
• 関連するPDBエントリー: 3IPS 3IPU
• 分子名称: Oxysterols receptor LXR-alpha, Nuclear receptor coactivator 1, [3-(3-{[2-chloro-3-(trifluoromethyl)benzyl](2,2-diphenylethyl)amino}propoxy)phenyl]acetic acid, ... (5 entities in total)
• 機能のキーワード: nuclear receptor, lxr homodimer, lxr signaling, alternative splicing, dna-binding, metal-binding, nucleus, polymorphism, receptor, transcription, transcription regulation, zinc, zinc-finger, activator, acyltransferase, chromosomal rearrangement, isopeptide bond, phosphoprotein, proto-oncogene, transferase, ubl conjugation
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Nucleus (Potential): Q13133; Nucleus (By similarity): Q15788
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 36350.67

構造登録者

Fradera, X.,Vu, D.,Nimz, O.,Skene, R.,Hosfield, D.,Wijnands, R.,Cooke, A.J.,Haunso, A.,King, A.,Bennet, D.J.,McGuire, R.,Uitdehaag, J.C.M. (登録日: 2009-08-18, 公開日: 2010-06-02, 最終更新日: 2024-04-03)

主引用文献

Fradera, X.,Vu, D.,Nimz, O.,Skene, R.,Hosfield, D.,Wynands, R.,Cooke, A.J.,Haunso, A.,King, A.,Bennett, D.J.,McGuire, R.,Uitdehaag, J.C.
X-ray structures of the LXRalpha LBD in its homodimeric form and implications for heterodimer signaling.
J.Mol.Biol., 399:120-132, 2010

PubMed Abstract: Liver X receptors (LXRs) are nuclear receptors that are central regulators of cholesterol homeostasis, and synthetic LXR agonists have shown promise as promoters of reverse cholesterol transport and anti-inflammatory agents. Here, we present three X-ray structures of three different agonists bound to the ligand binding domain of LXRalpha. These compounds are GW3965, F(3)methylAA, and a benzisoxazole urea, and we show that these diverse chemical scaffolds address common structural themes, leading to high binding affinity for LXR. Our structures show the LXRalpha ligand binding domain in its homodimeric form, an arrangement previously thought to be stereochemically difficult. A comparison with existing structures of the LXRbeta homodimer and LXRalpha:RXR (retinoid X receptor) heterodimers explains differences in dimer affinity and leads us to propose a model for allosteric activation in nuclear receptor dimers, in which an unactivated RXR partner provides an inhibitory tail wrap to the cofactor binding pocket of LXR.

PubMed: 20382159
DOI: 10.1016/j.jmb.2010.04.005

実験手法

X-RAY DIFFRACTION (2 Å)