title: New Insights into Human 17β-Hydroxysteroid Dehydrogenase Type 14: First Crystal Structures in Complex with a Steroidal Ligand and with a Potent Nonsteroidal Inhibitor.
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.
authors.affiliation: Institute for Pharmaceutical Chemistry, Philipps University Marburg , 35037 Marburg, Germany.
authors.forename: Nicole
authors.initials: N
authors.lastname: Bertoletti
authors.affiliation: Institute for Pharmaceutical Chemistry, Philipps University Marburg , 35037 Marburg, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Braun
authors.affiliation: Institute for Pharmaceutical Chemistry, Philipps University Marburg , 35037 Marburg, Germany.
authors.forename: Mahalia
authors.initials: M
authors.lastname: Lepage
authors.affiliation: German Research Center for Environmental Health, Institute of Experimental Genetics, Genome Analysis Center, Helmholtz Zentrum München , 85764 Neuherberg, Germany.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Möller
authors.affiliation: German Research Center for Environmental Health, Institute of Experimental Genetics, Genome Analysis Center, Helmholtz Zentrum München , 85764 Neuherberg, Germany.|Lehrstuhl für Experimentelle Genetik, Technische Universität München , 85350 Freising-Weihenstephan, Germany.|German Center for Diabetes Research (DZD) , 85764 Neuherberg, Germany.
authors.forename: Jerzy
authors.initials: J
authors.lastname: Adamski
authors.affiliation: Institute for Pharmaceutical Chemistry, Philipps University Marburg , 35037 Marburg, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Heine
authors.affiliation: Institute for Pharmaceutical Chemistry, Philipps University Marburg , 35037 Marburg, Germany.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Klebe
authors.affiliation: Institute for Pharmaceutical Chemistry, Philipps University Marburg , 35037 Marburg, Germany.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Marchais-Oberwinkler
mesh_terms: D015067:17-Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D018360:Crystallography, X-Ray; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D015394:Molecular Structure; D011725:Pyridines / Q000737:chemistry / Q000494:pharmacology*; D013256:Steroids / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D008024:Ligands; D011725:Pyridines; D013256:Steroids; C000620017:dihydroxyphenylpyridine methanone; D015067:17-Hydroxysteroid Dehydrogenases; C044256:3 (or 17)-beta-hydroxysteroid dehydrogenase