1SQN

Progesterone Receptor Ligand Binding Domain with bound Norethindrone

1SQN の概要

• エントリーDOI: 10.2210/pdb1sqn/pdb
• 関連するPDBエントリー: 1A28 1E3K 1ZYX
• 分子名称: progesterone receptor, (14beta,17alpha)-17-ethynyl-17-hydroxyestr-4-en-3-one (3 entities in total)
• 機能のキーワード: progesterone receptor; nuclear receptor; steroid receptor; norethindrone; birth control, hormone-growth factor receptor complex, hormone/growth factor receptor
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Nucleus. Isoform A: Nucleus. Isoform 4: Mitochondrion outer membrane : P06401
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 60865.39

構造登録者

Williams, S.P.,Madauss, K.P.,Deng, J.-S.,Austin, R.J.H.,Lambert, M.H.,McLay, I.,Pritchard, J.,Short, S.A.,Stewart, E.L.,Uings, I.J. (登録日: 2004-03-19, 公開日: 2004-07-27, 最終更新日: 2023-08-23)

主引用文献

Madauss, K.P.,Deng, J.-S.,Austin, R.J.H.,Lambert, M.H.,McLay, I.,Pritchard, J.,Short, S.A.,Stewart, E.L.,Uings, I.J.,Williams, S.P.
Progesterone receptor ligand binding pocket flexibility: crystal structures of the norethindrone and mometasone furoate complexes
J.Med.Chem., 47:3381-3387, 2004

PubMed Abstract: Although progesterone, the natural ligand of the progesterone receptor (PR), has a hydrogen atom at the 17alpha position, other potent steroid agonists such as norethindrone and mometasone furoate have larger substituents at this position that are accommodated by the PR ligand binding pocket. Crystallographic analysis of PR ligand binding domain complexes clearly demonstrated that these moieties were accommodated by local shifts of the protein main chain and by adoption of alternative side chain rotamer conformations of ligand-proximal amino acids. These conformational changes imparted a ligand-specific volume to the binding pocket, from 490 A3 in the metribolone complex to 520 A3 in the norethindrone complex, 565 A3 in the progesterone complex, and 730 A3 in the mometasone furoate complex. Despite these marked alterations in binding pocket volume, critical interactions essential for establishment of an active AF2 conformation were maintained.

PubMed: 15189034
DOI: 10.1021/jm030640n

実験手法

X-RAY DIFFRACTION (1.451 Å)