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

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• 作者：Nicole Bertoletti ; Florian Braun ; Mahalia Lepage ; Gabriele Möller ; Jerzy Adamski ; Andreas Heine ; Gerhard Klebe ; Sandrine Marchais-Oberwinkler
• 刊名：Journal of Medicinal Chemistry
• 出版年：2016
• 出版时间：July 28, 2016
• 年：2016
• 卷：59
• 期：14
• 页码：6961-6967
• 全文大小：333K
• 年卷期：0
• ISSN：1520-4804

文摘

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.