Crystal structure of the cofactor-free form of thioredoxin reductase from Acinetobacter baumannii

[摘要] Thioredoxin reductase (TrxR) is a central component in the thioredoxin system by involving in catalyzing the reduction of thioredoxin, which is critical for organism survival. Because this system is essential, it is a promising target for novel antimicrobial agents. Herein, we solved the 1.9 Å high-resolution structure of TrxR from Acinetobacter   baumannii Thioredoxin reductase ( Ab TrxR), which is a Gram-negative, pathogenic bacterium and a drug-resistant superbug. Ab TrxR was cofactor-free and formed a dimer in solution. Ab TrxR contained a longer dimerization loop2 and a shorter β 7 -β 8 connecting loop than other TrxRs. Ab TrxR cofactor-free form exhibited a flavin-oxidizing (FO) conformation, whose NADPH domain was located close to the dimeric interface. This structural information might be helpful for development of new antibiotic agents targeting superbugs.

[关键词] Acinetobacter baumannii;crystal structure;redox homeostasis;superbugs;thioredoxin reductase