3ERT

HUMAN ESTROGEN RECEPTOR ALPHA LIGAND-BINDING DOMAIN IN COMPLEX WITH 4-HYDROXYTAMOXIFEN

「2ERT」から置き換えられました

3ERT の概要

• エントリーDOI: 10.2210/pdb3ert/pdb
• 分子名称: PROTEIN (ESTROGEN RECEPTOR ALPHA), 4-HYDROXYTAMOXIFEN (3 entities in total)
• 機能のキーワード: nuclear receptor, transcription factor, estrogen, antagonist
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Isoform 1: Nucleus. Isoform 3: Nucleus: P03372
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 30237.73

構造登録者

Shiau, A.K.,Barstad, D.,Loria, P.M.,Cheng, L.,Kushner, P.J.,Agard, D.A.,Greene, G.L. (登録日: 1999-03-30, 公開日: 1999-04-08, 最終更新日: 2023-09-06)

主引用文献

Shiau, A.K.,Barstad, D.,Loria, P.M.,Cheng, L.,Kushner, P.J.,Agard, D.A.,Greene, G.L.
The structural basis of estrogen receptor/coactivator recognition and the antagonism of this interaction by tamoxifen.
Cell(Cambridge,Mass.), 95:927-937, 1998

PubMed Abstract: Ligand-dependent activation of transcription by nuclear receptors (NRs) is mediated by interactions with coactivators. Receptor agonists promote coactivator binding, and antagonists block coactivator binding. Here we report the crystal structure of the human estrogen receptor alpha (hER alpha) ligand-binding domain (LBD) bound to both the agonist diethylstilbestrol (DES) and a peptide derived from the NR box II region of the coactivator GRIP1 and the crystal structure of the hER alpha LBD bound to the selective antagonist 4-hydroxytamoxifen (OHT). In the DES-LBD-peptide complex, the peptide binds as a short alpha helix to a hydrophobic groove on the surface of the LBD. In the OHT-LBD complex, helix 12 occludes the coactivator recognition groove by mimicking the interactions of the NR box peptide with the LBD. These structures reveal the two distinct mechanisms by which structural features of OHT promote this "autoinhibitory" helix 12 conformation.

PubMed: 9875847
DOI: 10.1016/S0092-8674(00)81717-1

実験手法

X-RAY DIFFRACTION (1.9 Å)