5M5J

Thioredoxin reductase from Giardia duodenalis

5M5J の概要

• エントリーDOI: 10.2210/pdb5m5j/pdb
• 分子名称: Thioredoxin reductase, FLAVIN-ADENINE DINUCLEOTIDE, SODIUM ION, ... (4 entities in total)
• 機能のキーワード: reductase, flavoprotein, oxidoreductase
• 由来する生物種: Giardia intestinalis
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 71968.00

構造登録者

Fiorillo, A.,Ilari, A.,Lalle, M. (登録日: 2016-10-21, 公開日: 2017-05-17, 最終更新日: 2024-01-17)

主引用文献

Brogi, S.,Fiorillo, A.,Chemi, G.,Butini, S.,Lalle, M.,Ilari, A.,Gemma, S.,Campiani, G.
Structural characterization of Giardia duodenalis thioredoxin reductase (gTrxR) and computational analysis of its interaction with NBDHEX.
Eur J Med Chem, 135:479-490, 2017

PubMed Abstract: Giardia duodenalis is a microaerophilic parasite that colonizes the upper portions of the small intestine of humans. Giardia infection is a major contributor to diarrheal disease worldwide. Nitroheterocycles (e.g. metronidazole) or benzimidazoles (e.g. albendazole) are the most commonly used therapeutic agents. Unfortunately, their efficacy is reduced by low compliance or resistance phenomena. We recently discovered that the antitumoral drug 6-(7-nitro-2,1,3-benzoxadiazol-4-ylthio)hexanol (NBDHEX) is active against G. duodenalis trophozoites and its mode of action is linked to inhibition of thioredoxin reductase (gTrxR), a key component of Giardia redox system: gTrxR provides efficient defenses against reactive oxygen species (ROS), it is a target of 5-nitroimidazoles antiparasitic drugs and also contributes to their metabolism. However, the exact mechanism responsible for the gTrxR inhibition mediated by this chemical class of antigiardial compounds is yet to be defined. The definition of the structural determinants of activity against gTrxR could be important for the identification of novel drugs endowed with an innovative mode of action. With this aim, we solved the crystal structure of gTrxR and we analyzed in silico the binding mode of NBDHEX. The data presented herein could guide the development of NBDHEX derivatives tailored for selective inhibition of gTrxR as antigiardial agents.

PubMed: 28477573
DOI: 10.1016/j.ejmech.2017.04.057

実験手法

X-RAY DIFFRACTION (2.65 Å)