Structural aspects of agonism and antagonism in the oestrogen receptor

We have determined the three-dimensional structures of both alpha- and beta -forms of the ligand-binding domain of the oestrogen receptor (ER) in compl exes with a range of receptor agonists and antagonists. Here, we summarize how these structures provide both an understanding of the ER's distinctive pharmacophore and a rationale for its ability to hind a diverse range of ch emically distinct compounds. In addition, these studies provide a unique in sight into the mechanisms that underlie receptor activation, as well as pro viding a structural basis for the antagonist action of molecules, such as r aloxifene.