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Proteins, Expression, Isolation and Analysis | Page 1. 1 Aspergillus fumigatus thioredoxin reductase: structure, 1 mechanism, and inhibition 2 3 Andrew C. Marshall1, Sarah E. Kidd2, Stephanie J. Lamont-Friedrich3, Georgia 4 Arentz4, Peter Hoffmann4, Bryan R. Coad3,5, and John B. Bruning1,* 5 6 7 …with an N-terminal hexahistidine tag was purchased from GenScript (Piscataway, NJ, USA). | Get A Quote |
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 comple... More