Structural highlights
Function
[DHB14_HUMAN] Has NAD-dependent 17-beta-hydroxysteroid dehydrogenase activity. Converts oestradiol to oestrone. The physiological substrate is not known. Acts on oestradiol and 5-androstene-3-beta,17-beta-diol (in vitro).[1]
Publication Abstract from PubMed
17beta-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.
New Insights into Human 17beta-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 J Med Chem. 2016 Jul 12. PMID:27362750[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Lukacik P, Keller B, Bunkoczi G, Kavanagh KL, Lee WH, Adamski J, Oppermann U. Structural and biochemical characterization of human orphan DHRS10 reveals a novel cytosolic enzyme with steroid dehydrogenase activity. Biochem J. 2007 Mar 15;402(3):419-27. PMID:17067289 doi:BJ20061319
- ↑ Bertoletti N, Braun F, Lepage M, Moller G, Adamski J, Heine A, Klebe G, Marchais-Oberwinkler S. New Insights into Human 17beta-Hydroxysteroid Dehydrogenase Type 14: First Crystal Structures in Complex with a Steroidal Ligand and with a Potent Nonsteroidal Inhibitor. J Med Chem. 2016 Jul 12. PMID:27362750 doi:http://dx.doi.org/10.1021/acs.jmedchem.6b00293
