Differential presentation of protein interaction surfaces on the androgen receptor defines the pharmacological actions of bound ligands

Chem Biol. 2009 Apr 24;16(4):452-60. doi: 10.1016/j.chembiol.2009.01.016.


The pharmacological activity of different nuclear receptor ligands is reflected by their impact on receptor structure. Thus, we asked whether differential presentation of protein-protein interaction surfaces on the androgen receptor (AR), a surrogate assay of receptor conformation, could be used in a prospective manner to define the pharmacological activity of bound ligands. To this end, we identified over 150 proteins/polypeptides whose ability to interact with AR is influenced in a differential manner by ligand binding. The most discriminatory of these protein-AR interactions were used to develop a robust compound-profiling tool that enabled the separation of ligands into functionally distinguishable classes. Importantly, the ligands within each class exhibited similar pharmacological activities, a result that highlights the relationship between receptor structure and activity and provides direction for the discovery of novel AR modulators.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Humans
  • Ligands*
  • Protein Binding
  • Protein Conformation / drug effects
  • Protein Interaction Mapping
  • Receptors, Androgen / chemistry
  • Receptors, Androgen / genetics
  • Receptors, Androgen / metabolism*
  • Structure-Activity Relationship
  • Transcription, Genetic / drug effects


  • Ligands
  • Receptors, Androgen