New Insights into Human 17 beta-Hydroxysteroid Dehydrogenase Type 14: First Crystal Structures in Complex with a Steroidal Ligand and with a Potent Nonsteroidal Inhibitor

作者：Bertoletti Nicole; Braun Florian; Lepage Mahalia; Moeller Gabriele; Adamski Jerzy; Heine Andreas; Klebe Gerhard; Marchais Oberwinkler Sandrine^*

来源：Journal of Medicinal Chemistry, 2016, 59(14): 6961-6967.

DOI：10.1021/acs.jmedchem.6b00293

17 beta-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, nonsteroidal 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.

• 出版日期2016-7-28