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

被引：14

作者：

Bertoletti, Nicole ^{[1
]}

Braun, Florian ^{[1
]}

Lepage, Mahalia ^{[1
]}

Moeller, Gabriele ^{[2
]}

Adamski, Jerzy ^{[2
,3
,4
]}

Heine, Andreas ^{[1
]}

Klebe, Gerhard ^{[1
]}

Marchais-Oberwinkler, Sandrine ^{[1
]}

机构：

[1] Univ Marburg, Inst Pharmaceut Chem, D-35037 Marburg, Germany

[2] Helmholtz Zentrum Munchen, Genome Anal Ctr, Inst Expt Genet, German Res Ctr Environm Hlth, D-85764 Neuherberg, Germany

[3] Tech Univ Munich, Lehrstuhl Expt Genet, D-85350 Freising Weihenstephan, Germany

[4] German Ctr Diabet Res DZD, D-85764 Neuherberg, Germany

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2016年 / 59卷 / 14期

关键词：

STABILITY;

D O I：

10.1021/acs.jmedchem.6b00293

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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.

引用

页码：6961 / 6967

页数：7

共 17 条

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