1ERE

HUMAN ESTROGEN RECEPTOR LIGAND-BINDING DOMAIN IN COMPLEX WITH 17BETA-ESTRADIOL

1ERE の概要

• エントリーDOI: 10.2210/pdb1ere/pdb
• 分子名称: ESTROGEN RECEPTOR, ESTRADIOL (3 entities in total)
• 機能のキーワード: nuclear receptor, transcription factor, steroid, agonist
• 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: 6
• 化学式量合計: 174968.42

構造登録者

Brzozowski, A.M.,Pike, A.C.W. (登録日: 1997-09-08, 公開日: 1998-09-16, 最終更新日: 2024-02-07)

主引用文献

Brzozowski, A.M.,Pike, A.C.,Dauter, Z.,Hubbard, R.E.,Bonn, T.,Engstrom, O.,Ohman, L.,Greene, G.L.,Gustafsson, J.A.,Carlquist, M.
Molecular basis of agonism and antagonism in the oestrogen receptor.
Nature, 389:753-758, 1997

PubMed Abstract: Oestrogens are involved in the growth, development and homeostasis of a number of tissues. The physiological effects of these steroids are mediated by a ligand-inducible nuclear transcription factor, the oestrogen receptor (ER). Hormone binding to the ligand-binding domain (LBD) of the ER initiates a series of molecular events culminating in the activation or repression of target genes. Transcriptional regulation arises from the direct interaction of the ER with components of the cellular transcription machinery. Here we report the crystal structures of the LBD of ER in complex with the endogenous oestrogen, 17beta-oestradiol, and the selective antagonist raloxifene, at resolutions of 3.1 and 2.6 A, respectively. The structures provide a molecular basis for the distinctive pharmacophore of the ER and its catholic binding properties. Agonist and antagonist bind at the same site within the core of the LBD but demonstrate different binding modes. In addition, each class of ligand induces a distinct conformation in the transactivation domain of the LBD, providing structural evidence of the mechanism of antagonism.

PubMed: 9338790
DOI: 10.1038/39645

実験手法

X-RAY DIFFRACTION (3.1 Å)