4WDT

17beta-HSD5 in complex with 2-nitro-5-(phenylsulfonyl)phenol

4WDT の概要

• エントリーDOI: 10.2210/pdb4wdt/pdb
• 関連するPDBエントリー: 4WDS 4WDU 4WDV 4WDW 4WDX
• 分子名称: Aldo-keto reductase family 1 member C3, NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, 2-nitro-5-(phenylsulfonyl)phenol, ... (4 entities in total)
• 機能のキーワード: aldo-keto reductase inhibitor, oxidoreductase-oxidoreductase inhibitor complex, oxidoreductase/oxidoreductase inhibitor
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 38990.03

構造登録者

Amano, Y.,Yamaguchi, T. (登録日: 2014-09-09, 公開日: 2015-04-15, 最終更新日: 2024-06-26)

主引用文献

Amano, Y.,Yamaguchi, T.,Niimi, T.,Sakashita, H.
Structures of complexes of type 5 17 beta-hydroxysteroid dehydrogenase with structurally diverse inhibitors: insights into the conformational changes upon inhibitor binding.
Acta Crystallogr.,Sect.D, 71:918-927, 2015

PubMed Abstract: Type 5 17β-hydroxysteroid dehydrogenase (17β-HSD5) is an aldo-keto reductase expressed in the human prostate which catalyzes the conversion of androstenedione to testosterone. Testosterone is converted to 5α-dihydrotestosterone, which is present at high concentrations in patients with castration-resistant prostate cancer (CRPC). Inhibition of 17β-HSD5 is therefore considered to be a promising therapy for treating CRPC. In the present study, crystal structures of complexes of 17β-HSD5 with structurally diverse inhibitors derived from high-throughput screening were determined. In the structures of the complexes, various functional groups, including amide, nitro, pyrazole and hydroxyl groups, form hydrogen bonds to the catalytic residues His117 and Tyr55. In addition, major conformational changes of 17β-HSD5 were observed following the binding of the structurally diverse inhibitors. These results demonstrate interactions between 17β-HSD5 and inhibitors at the atomic level and enable structure-based drug design for anti-CRPC therapy.

PubMed: 25849402
DOI: 10.1107/S1399004715002175

実験手法

X-RAY DIFFRACTION (1.5 Å)