|Figure 7: AR mechanism of antagonism is disrupted by disease mutations. Many clinical mutations
widen the pocket, allowing large antagonist ligands to bind without perturbing H12,
converting antagonists to agonists. A) Wild-type AR with DHT ligand (PDB 1I37) with
cavity shown in
black. B) T877A mutation (PDB 1I38) introduces the smaller alanine sidechain, increasing
(yellow) compared to wild-type AR (black). C) W741L mutation widens cavity (yellow)
by replacing bulky
tryptophan sidechain with leucine.