Bertoletti Nicole, Braun Florian, Lepage Mahalia, Möller Gabriele, Adamski Jerzy, Heine Andreas, Klebe Gerhard, Marchais-Oberwinkler Sandrine
Institute for Pharmaceutical Chemistry, Philipps University Marburg , 35037 Marburg, Germany.
German Research Center for Environmental Health, Institute of Experimental Genetics, Genome Analysis Center, Helmholtz Zentrum München , 85764 Neuherberg, Germany.
J Med Chem. 2016 Jul 28;59(14):6961-7. doi: 10.1021/acs.jmedchem.6b00293. Epub 2016 Jul 12.
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.
17β-羟基类固醇脱氢酶14是一种短链脱氢酶/还原酶（SDR）酶，能够利用烟酰胺腺嘌呤二核苷酸（NAD(+)）氧化雌二醇和5-雄烯二醇。我们测定了这种人类酶的全酶形式以及与雌酮和第一种强效非甾体抑制剂形成的三元复合物的晶体结构。这些结构揭示了一个呈圆锥形、相当大且具有亲脂性的结合位点，是基于结构的抑制剂设计的起点。对两种天然变体（S205和T205）进行了表征，它们具有相似的结构。
