Homology modeling meets site-directed mutagenesis: An ideal combination to elucidate the topology of 17β-HSD2.

17β-Hydroxysteroid dehydrogenase type 2 (17β-HSD2) catalyzes the conversion of highly active estrogens and androgens into their less active forms using NAD as cofactor. Substrate and cofactor specificities of 17β-HSD2 have been reported and potent 17β-HSD2 inhibitors have been discovered in a ligand-based approach. However, the molecular basis and the amino acids involved in the enzymatic functionality are poorly understood, as no crystal structure of the membrane-associated 17β-HSD2 exists.