1L2J

Human Estrogen Receptor beta Ligand-binding Domain in Complex with (R,R)-5,11-cis-diethyl-5,6,11,12-tetrahydrochrysene-2,8-diol

1L2J の概要

• エントリーDOI: 10.2210/pdb1l2j/pdb
• 関連するPDBエントリー: 1L2I 1QKM
• 分子名称: ESTROGEN RECEPTOR BETA, (R,R)-5,11-CIS-DIETHYL-5,6,11,12-TETRAHYDROCHRYSENE-2,8-DIOL (3 entities in total)
• 機能のキーワード: nuclear receptor, transcription factor, estrogen, antagonist, transcription receptor
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Nucleus: Q92731
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 61783.09

構造登録者

Shiau, A.K.,Barstad, D.,Radek, J.T.,Meyers, M.J.,Nettles, K.W.,Katzenellenbogen, B.S.,Katzenellenbogen, J.A.,Agard, D.A.,Greene, G.L. (登録日: 2002-02-21, 公開日: 2002-05-01, 最終更新日: 2023-08-16)

主引用文献

Shiau, A.K.,Barstad, D.,Radek, J.T.,Meyers, M.J.,Nettles, K.W.,Katzenellenbogen, B.S.,Katzenellenbogen, J.A.,Agard, D.A.,Greene, G.L.
Structural characterization of a subtype-selective ligand reveals a novel mode of estrogen receptor antagonism.
Nat.Struct.Biol., 9:359-364, 2002

PubMed Abstract: The R,R enantiomer of 5,11-cis-diethyl-5,6,11,12-tetrahydrochrysene-2,8-diol (THC) exerts opposite effects on the transcriptional activity of the two estrogen receptor (ER) subtypes, ER alpha and ER beta. THC acts as an ER alpha agonist and as an ER beta antagonist. We have determined the crystal structures of the ER alpha ligand binding domain (LBD) bound to both THC and a fragment of the transcriptional coactivator GRIP1, and the ER beta LBD bound to THC. THC stabilizes a conformation of the ER alpha LBD that permits coactivator association and a conformation of the ER beta LBD that prevents coactivator association. A comparison of the two structures, taken together with functional data, reveals that THC does not act on ER beta through the same mechanisms used by other known ER antagonists. Instead, THC antagonizes ER beta through a novel mechanism we term 'passive antagonism'.

PubMed: 11953755

実験手法

X-RAY DIFFRACTION (2.95 Å)