DsbA1

DsbA1 is a periplasmic thiol-disulfide oxidoreductase found in bacteria, belonging to the DsbA family. In organisms that carry multiple dsbA genes, DsbA1 denotes one paralog that may differ from other DsbA proteins in substrate preference or regulation. The enzyme is directed to the periplasm by an N-terminal signal peptide and mature forms a thioredoxin-like fold that includes a catalytic CXXC active-site motif essential for its redox activity.

Mechanistically, DsbA1 catalyzes the formation of disulfide bonds in newly exported or periplasmic proteins. It donates oxidizing equivalents to substrate proteins and becomes reduced in the process; it is subsequently reoxidized by the membrane-bound partner DsbB, enabling continuous turnover. Through this cycle, DsbA1 contributes to the proper folding of a broad range of periplasmic and secreted proteins, including virulence factors such as adhesins, toxins, and outer membrane components in many pathogens.

DsbA1 often coexists with other dsbA paralogs, such as DsbA2, and with dsbB, forming part of the broader oxidative folding network in the bacterial envelope. Substrate specificity, redox potential, and expression control can vary among paralogs and across species, reflecting adaptation to different cellular needs and environmental conditions. Structural studies emphasize a conserved thioredoxin-like core with the active-site motif, while surface features can influence interactions with diverse substrates.

Given its central role in oxidative protein folding, DsbA1 is of interest in microbiology and antimicrobial research. Disruption of dsbA1 can impair the maturation of virulence-associated proteins, reducing pathogenicity in some bacteria and offering a potential avenue for anti-virulence strategies.