6BPY

Aspergillus fumigatus Thioredoxin Reductase

6BPY の概要

• エントリーDOI: 10.2210/pdb6bpy/pdb
• 分子名称: Thioredoxin reductase, FLAVIN-ADENINE DINUCLEOTIDE, MALONATE ION, ... (8 entities in total)
• 機能のキーワード: redox homeostasis, rossmann fold, dithiol, oxidoreductase
• 由来する生物種: Neosartorya fumigata (Aspergillus fumigatus)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 83921.58

構造登録者

Marshall, A.C.,Bruning, J.B. (登録日: 2017-11-27, 公開日: 2019-01-09, 最終更新日: 2024-10-30)

主引用文献

Marshall, A.C.,Kidd, S.E.,Lamont-Friedrich, S.J.,Arentz, G.,Hoffmann, P.,Coad, B.R.,Bruning, J.B.
Structure, Mechanism, and Inhibition ofAspergillus fumigatusThioredoxin Reductase.
Antimicrob.Agents Chemother., 63:-, 2019

PubMed Abstract: infections are associated with high mortality rates and high treatment costs. Limited available antifungals and increasing antifungal resistance highlight an urgent need for new antifungals. Thioredoxin reductase (TrxR) is essential for maintaining redox homeostasis and presents as a promising target for novel antifungals. We show that ebselen [2-phenyl-1,2-benzoselenazol-3(2H)-one] is an inhibitor of TrxR ( = 0.22 μM) and inhibits growth of spp., with MIC values of 16 to 64 µg/ml. Mass spectrometry analysis demonstrates that ebselen interacts covalently with a catalytic cysteine of TrxR, Cys148. We also present the X-ray crystal structure of TrxR and use modeling of the enzyme-inhibitor complex to outline key molecular interactions. This provides a scaffold for future design of potent and selective antifungal drugs that target TrxR, improving the potency of ebselen toward inhbition of growth.

PubMed: 30642940
DOI: 10.1128/AAC.02281-18

実験手法

X-RAY DIFFRACTION (3.201 Å)