Download MendeleyNew Insights into Human 17 beta-Hydroxysteroid Dehydrogenase Type 14: First Crystal Structures in Complex with a Steroidal Ligand and with a Potent Nonsteroidal Inhibitor.
Bertoletti, N., Braun, F., Lepage, M., Moller, G., Adamski, J., Heine, A., Klebe, G., Marchais-Oberwinkler, S.(2016) J Med Chem 59: 6961-6967
- PubMed: 27362750
- DOI: https://doi.org/10.1021/acs.jmedchem.6b00293
- Primary Citation of Related Structures:
5HS6, 5ICM, 5ICS, 5JS6, 5JSF - PubMed Abstract:
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, 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.
Organizational Affiliation:
Institute for Pharmaceutical Chemistry, Philipps University Marburg , 35037 Marburg, Germany.
