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 complexes 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 bind a diverse range of chemically distinct compounds. In addition, these studies provide a unique insight into the mechanisms that underlie receptor activation, as well as providing a structural basis for the antagonist action of molecules, such as raloxifene.
Pike
A C
AC
Structural Biology Laboratory, Chemistry Department, University of York, York YO10 5DD, U.K.
Brzozowski
A M
AM
Walton
J
J
Hubbard
R E
RE
Bonn
T
T
Gustafsson
J A
JA
Carlquist
M
M
D000818:Animals; D001665:Binding Sites; D008024:Ligands; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D020849:Raloxifene Hydrochloride / Q000494:pharmacology; D011960:Receptors, Estrogen / Q000819:agonists* / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology
D008024:Ligands; D011960:Receptors, Estrogen; D020845:Selective Estrogen Receptor Modulators; D020849:Raloxifene Hydrochloride