Comparison of the structure and activity of thioredoxin 2 and thioredoxin 1 from Acinetobacter baumannii.

Thioredoxin (Trx) is essential in a redox-control system, with many bacteria containing two Trxs: Trx1 and Trx2. Due to a Trx system's critical function, Trxs are targets for novel antibiotics. Here, a 1.20 Šhigh-resolution structure of Trx2 from Acinetobacter baumannii (abTrx2), an antibiotic resistant pathogenic superbug, is elucidated. By comparing Trx1 and Trx2, it is revealed that the two Trxs possess similar activity, although Trx2 contains an additional N-terminal zinc-finger domain and exhibits more flexible properties in solution. Finally, it is shown that the Trx2 zinc-finger domain might be rotatable and that proper zinc coordination at the zinc-finger domain is critical to abTrx2 activity. This study enhances understanding of the Trx system and will facilitate the design of novel antibiotics.

High-resolution crystal structure of Acinetobacter baumannii thioredoxin 1.

Thioredoxin (Trx) is a central component of the redox control system that maintains the redox homeostasis critical for organism survival. Owing to its central role in survival, Trx is a prospective target for novel antimicrobial agents. Herein, we report a 1.45 Å high-resolution structure of Trx1 of Acinetobacter baumannii (abTrx1), an antibiotic-resistant pathogenic superbug. Although abTrx1 exhibited the canonical Trx fold, which consists of a four-stranded ß-sheet surrounded by four α-helices, structural differences were detected in the loop forming the C-X-X-C redox center and the C-terminal. The unique CAPC sequence of the C-X-X-C motif in the abTrx1 redox center was characterized by mutagenesis. This study contributes to the field of drug designing against superbugs.

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

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 (AbTrxR), which is a Gram-negative, pathogenic bacterium and a drug-resistant superbug. AbTrxR was cofactor-free and formed a dimer in solution. AbTrxR contained a longer dimerization loop2 and a shorter ß7 -ß8 connecting loop than other TrxRs. AbTrxR 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.