Resistant Superbugs: Race against Time

Kumar, Mohit

doi:10.1017/ice.2015.318

Cited by 11 publications

(5 citation statements)

References 4 publications

(7 reference statements)

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“…Acinetobacter baumannii is a rod‐shaped, Gram‐negative, pathogenic bacterium that causes hospital‐derived infections in humans [19]. This bacterium is one of the well‐known multiple drug‐resistant superbugs, which are considered one of the biggest threats to global public health [20,21]. The need for the development of new antibiotic agents that target superbugs has been emphasized in the last few decades [22].…”

Section: Figmentioning

confidence: 99%

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

2021

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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 β7‐β8 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.

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Section: Figmentioning

confidence: 99%

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

2021

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“…Acinetobacter baumannii is one of many drug-resistant superbugs, which are considered one of the biggest threats to public health globally (Kumar, 2016;Burki, 2018), and also causes hospital-acquired infections in humans (Antunes et al, 2014). The importance of developing next-generation antibiotic agents that target superbugs has been highlighted recently, and efforts to do so are ongoing (Wright, 2000).…”

Section: Introductionmentioning

confidence: 99%

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

Chang

Sung

Lee

et al. 2023

Int Union Crystallogr J

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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 Å high-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.

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“…The need for the development of new antibiotic agents has recently been emphasized because of the emergence of superbugs, which are antibiotic-resistant bacteria that are considered to be one of the greatest threats to global public health (Kumar, 2016;Burki, 2018). For example, Acinetobacter baumannii, a typical rod-shaped Gram-negative bacterium, is a human pathogen that causes hospital-derived infections and occasionally exhibits multiple drug resistance.…”

Section: Introductionmentioning

confidence: 99%

Putative hexameric glycosyltransferase functional unit revealed by the crystal structure of Acinetobacter baumannii MurG

Jung

Kwon

Kim

et al. 2021

Int Union Crystallogr J

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Lipid II, the main component of the bacterial cell wall, is synthesized by the addition of UDP-N-acetylglucosamine to the UDP-N-acetylmuramic acid pentapeptide catalyzed by the glycosyltransferase MurG. Owing to its critical role in cell-wall biosynthesis, MurG is considered to be an attractive target for antibacterial agents. Although the Mur family ligases have been extensively studied, the molecular mechanism of the oligomeric scaffolding assembly of MurG remains unclear. In this study, MurG from Acinetobacter baumannii (abMurG), a human pathogen, was characterized and its hexameric crystal structure was unveiled; this is the first homo-oligomeric structure to be described in the MurG family and the Mur family. Homogeneous protein samples were produced for structural studies using size-exclusion chromatography, the absolute molecular mass was calculated via multi-angle light scattering, and protein–protein interactions were analyzed using the PDBePISA server. abMurG was found to form homo-oligomeric complexes in solution, which might serve as functional units for the scaffolding activity of MurG. Furthermore, analysis of this structure revealed the molecular assembly mechanism of MurG. This structural and biochemical study elucidated the homo-oligomerization mechanism of MurG and suggests a new potential antibiotic target on MurG.

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Resistant Superbugs: Race against Time

Cited by 11 publications

References 4 publications

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

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

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

Putative hexameric glycosyltransferase functional unit revealed by the crystal structure of Acinetobacter baumannii MurG

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