TY - JOUR T1 - X-ray Crystallography of Estrogens and Their Binding to Receptor Sites JF - Molecular Pharmacology JO - Mol Pharmacol SP - 438 LP - 445 VL - 8 IS - 4 AU - MICHEL HOSPITAL AU - BERNARD BUSETTA AU - ROBERT BUCOURT AU - HADASSA WEINTRAUB AU - ETIENNE-EMILE BAULIEU Y1 - 1972/07/01 UR - http://molpharm.aspetjournals.org/content/8/4/438.abstract N2 - Estradiol, a natural estrogen and a relatively rigid molecule, and diethylstilbestrol, a synthetic, nonsteroidal estrogen and more flexible molecule, compete for the same sites of the uterus estrogen receptors in cytosol and non-histone chromatin protein preparations. When crystallized under certain conditions, these compounds have very different over-all structures. The stilbene derivative possesses a much thicker, more symmetrical structure, with a phenol group at each extremity of the molecule, and it is difficult to reconcile the difference in shape of these two estrogens with binding to the same receptor sites. However, when diethylstilbestrol is crystallized from methanol-water and from ethanol, each molecule is linked to 1 alcohol and 1 water molecule in the former case, and with a molecule of ethanol by two different hydrogen bonds in the latter. The molecule thus becomes asymmetrical and assumes a conformation more closely simulating estradiol, with two distinguishable oxygenhydrogen bonds. It is proposed that the solvated asymmetrical form of diethylstilbestrol resembles more closely its "active" conformation when present in receptor binding sites. This concept is compatible with the estrogenic activity and binding affinity of (a) the estradiol derivatives (11β-methoxy-7α-methyl), which closely resemble asymmetrical diethylstilbestrol structurally, and (b) the stilbene derivatives (4,4'-dihydroxy-7-ethyl-6',7'-dimethylstilbene and 4,4'-dihydroxy-7'-ethyl-6',7'-dimethylstilbene), which are more like estradiol in structure. ER -