2QZO

Crystal Structure of the Estrogen Receptor Alpha Ligand Binding Domain Complexed with WAY-169916

2QZO の概要

• エントリーDOI: 10.2210/pdb2qzo/pdb
• 関連するPDBエントリー: 2QXS
• 分子名称: Estrogen receptor, Nuclear receptor coactivator 2, 4-[1-allyl-7-(trifluoromethyl)-1H-indazol-3-yl]benzene-1,3-diol, ... (5 entities in total)
• 機能のキーワード: protein-ligand complex, dna-binding, lipid-binding, metal-binding, nucleus, phosphorylation, receptor, steroid-binding, transcription, transcription regulation, zinc-finger
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Isoform 1: Nucleus . Isoform 3: Nucleus. Nucleus: P03372 P03372; Nucleus : Q8BN74
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 62829.89

構造登録者

Bruning, J.B.,Gil, G.,Nowak, J.,Katzenellenbogen, J.,Nettles, K.W. (登録日: 2007-08-16, 公開日: 2008-08-26, 最終更新日: 2024-10-09)

主引用文献

Bruning, J.B.,Parent, A.A.,Gil, G.,Zhao, M.,Nowak, J.,Pace, M.C.,Smith, C.L.,Afonine, P.V.,Adams, P.D.,Katzenellenbogen, J.A.,Nettles, K.W.
Coupling of receptor conformation and ligand orientation determine graded activity.
Nat.Chem.Biol., 6:837-843, 2010

PubMed Abstract: Small molecules stabilize specific protein conformations from a larger ensemble, enabling molecular switches that control diverse cellular functions. We show here that the converse also holds true: the conformational state of the estrogen receptor can direct distinct orientations of the bound ligand. 'Gain-of-allostery' mutations that mimic the effects of ligand in driving protein conformation allowed crystallization of the partial agonist ligand WAY-169916 with both the canonical active and inactive conformations of the estrogen receptor. The intermediate transcriptional activity induced by WAY-169916 is associated with the ligand binding differently to the active and inactive conformations of the receptor. Analyses of a series of chemical derivatives demonstrated that altering the ensemble of ligand binding orientations changes signaling output. The coupling of different ligand binding orientations to distinct active and inactive protein conformations defines a new mechanism for titrating allosteric signaling activity.

PubMed: 20924370
DOI: 10.1038/nchembio.451

実験手法

X-RAY DIFFRACTION (1.72 Å)