1MVC

Crystal structure of the human RXR alpha ligand binding domain bound to the synthetic agonist compound BMS 649 and a coactivator peptide

1MVC の概要

• エントリーDOI: 10.2210/pdb1mvc/pdb
• 関連するPDBエントリー: 1FBY 1MV9
• 分子名称: RXR retinoid X receptor, Nuclear receptor coactivator 2, 4-[2-(5,5,8,8-TETRAMETHYL-5,6,7,8-TETRAHYDRO-NAPHTHALEN-2-YL)-[1,3]DIOXOLAN-2-YL]-BENZOIC ACID, ... (4 entities in total)
• 機能のキーワード: nuclear receptor, retinoic acid, agonist recognition, transcription factor, transcription
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Nucleus: P19793 Q15596
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 28815.37

構造登録者

Egea, P.F.,Mitschler, A.,Moras, D. (登録日: 2002-09-24, 公開日: 2002-10-16, 最終更新日: 2023-10-25)

主引用文献

Egea, P.F.,Mitschler, A.,Moras, D.
Molecular Recognition of Agonist Ligands by RXRs
MOL.ENDOCRINOL., 16:987-997, 2002

PubMed Abstract: The nuclear receptor RXR is an obligate partner in many signal transduction pathways. We report the high-resolution structures of two complexes of the human RXRalpha ligand-binding domain specifically bound to two different and chemically unrelated agonist compounds: docosa hexaenoic acid, a natural derivative of eicosanoic acid, present in mammalian cells and recently identified as a potential endogenous RXR ligand in the mouse brain, and the synthetic ligand BMS 649. In both structures the RXR-ligand-binding domain forms homodimers and exhibits the active conformation previously observed with 9-cis-RA. Analysis of the differences in ligand-protein contacts (predominantly van der Waals forces) and binding cavity geometries and volumes for the several agonist-bound RXR structures clarifies the structural features important for ligand recognition. The L-shaped ligand-binding pocket adapts to the diverse ligands, especially at the level of residue N306, which might thus constitute a new target for drug-design. Despite its highest affinity 9-cis-RA displays the lowest number of ligand-protein contacts. These structural results support the idea that docosa hexaenoic acid and related fatty acids could be natural agonists of RXRs and question the real nature of the endogenous ligand(s) in mammalian cells.

PubMed: 11981034
DOI: 10.1210/me.16.5.987

実験手法

X-RAY DIFFRACTION (1.9 Å)