Publications Search - Abstract View
||Differential presentation of protein interaction surfaces on the androgen receptor defines the pharmacological actions of bound ligands.
||Norris JD, Joseph JD, Sherk AB, Juzumiene D, Turnbull PS, Rafferty SW, Cui H, Anderson E, Fan D, Dye DA, Deng X, Kazmin D, Chang CY, Willson TM, McDonnell DP
||2009 Apr 24
||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.