1SQN

Progesterone Receptor Ligand Binding Domain with bound Norethindrone

Summary for 1SQN

• Entry DOI: 10.2210/pdb1sqn/pdb
• Related: 1A28 1E3K 1ZYX
• Descriptor: progesterone receptor, (14beta,17alpha)-17-ethynyl-17-hydroxyestr-4-en-3-one (3 entities in total)
• Functional Keywords: progesterone receptor; nuclear receptor; steroid receptor; norethindrone; birth control, hormone-growth factor receptor complex, hormone/growth factor receptor
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus. Isoform A: Nucleus. Isoform 4: Mitochondrion outer membrane : P06401
• Total number of polymer chains: 2
• Total formula weight: 60865.39

Authors

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. (deposition date: 2004-03-19, release date: 2004-07-27, Last modification date: 2023-08-23)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.451 Å)