Structural basis for agonism and antagonism for a set of chemically related progesterone receptor modulators

J Biol Chem. 2011 Oct 7;286(40):35079-86. doi: 10.1074/jbc.M111.273029. Epub 2011 Aug 17.


The progesterone receptor is able to bind to a large number and variety of ligands that elicit a broad range of transcriptional responses ranging from full agonism to full antagonism and numerous mixed profiles inbetween. We describe here two new progesterone receptor ligand binding domain x-ray structures bound to compounds from a structurally related but functionally divergent series, which show different binding modes corresponding to their agonistic or antagonistic nature. In addition, we present a third progesterone receptor ligand binding domain dimer bound to an agonist in monomer A and an antagonist in monomer B, which display binding modes in agreement with the earlier observation that agonists and antagonists from this series adopt different binding modes.

MeSH terms

  • Animals
  • Binding Sites
  • CHO Cells
  • Cricetinae
  • Cricetulus
  • Crystallography, X-Ray / methods
  • Dimerization
  • Drug Design
  • Drug Evaluation, Preclinical
  • Ligands
  • Mifepristone / chemistry
  • Models, Molecular
  • Molecular Conformation
  • Norethindrone / chemistry
  • Progesterone / chemistry
  • Protein Binding
  • Protein Conformation
  • Receptors, Progesterone / agonists*
  • Receptors, Progesterone / antagonists & inhibitors*
  • Receptors, Progesterone / metabolism*


  • Ligands
  • Receptors, Progesterone
  • Mifepristone
  • Progesterone
  • Norethindrone

Associated data

  • PDB/3ZR7
  • PDB/3ZRA
  • PDB/3ZRB