In recent years, the presence of ES in breast carcinomas and the ES-dependent proliferation of breast cancer cells have been demonstrated convincingly. Compounds that inhibit the activity of ES have shown promise in the prevention and treatment of breast tumors. The rational design of better, more selective inhibitors requires a detailed understanding of the molecular architecture of the enzyme's active site.

ES is localized in the endoplasmic reticulum, a network of membranes in the cell. The crystal structure reveals a transmembrane portion consisting of two anti-parallel alpha helices that protrude from the otherwise roughly spherical molecule, thereby giving it a "mushroom-like" shape. Presumably, these helices anchor the functional part of the molecule to the surface of the membrane. The entrance to the active site, buried deep in a cavity in the "gill" of the "mushroom", rests near the membrane surface. This architecture provides the first structural evidence for a possible active participation of the membrane matrix in steroidal substrate sequestration or product excretion processes. It remains to be determined whether or not this will provide a general model for the functioning of other membrane-associated enzymes involved in the biosynthesis of steroid hormones.

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