New insights into human 17β-hydroxysteroid dehydrogenase type 14: First crystal structures in complex with a steroidal ligand and with a potent non-steroidal inhibitor.

17β-HSD14 is a SDR enzyme, able to oxidize estradiol and 5-androstenediol using NAD(+). We determined the crystal structure of this human enzyme as the holo form and as ternary complexes with estrone and with the first potent, non-steroidal inhibitor. The structures reveal a conical, rather large and lipophilic binding site and are the starting point for structure-based inhibitor design. The two natural variants (S205 and T205) were characterized and adopt a similar structure