dsbA

DsbA is a thiol-disulfide oxidoreductase present in the periplasm of many Gram-negative bacteria. It catalyzes the formation of disulfide bonds in newly synthesized secretory and outer membrane proteins, enabling oxidative folding within the periplasm. DsbA belongs to the Dsb (disulfide bond) system that includes membrane-bound DsbB, which reoxidizes DsbA after it has donated its disulfide to substrate proteins. DsbA itself cycles between a disulfide-containing oxidized form and a reduced dithiol form; the active site features a conserved CXXC motif (commonly CGYC in Escherichia coli).

The oxidized DsbA oxidizes substrate cysteines, forming disulfide bonds and becoming reduced. DsbB reoxidizes DsbA by transferring electrons to the quinone pool of the inner membrane, linking disulfide bond formation to cellular respiration. Some organisms possess multiple DsbA homologs, such as DsbA1 and DsbA2, with varying substrate specificities. DsbA typically has a thioredoxin-like fold and is exported to the periplasm by the Sec pathway as a preprotein with an N-terminal signal peptide. The matured protein is about 20 kDa.

DsbA acts on a wide range of periplasmic and secreted proteins, including outer membrane proteins, pili, flagellar components, toxins, and enzymes. In pathogenic bacteria, DsbA is essential for proper folding of many virulence factors; disruption of dsbA often reduces virulence without impairing growth.

Because of its central role in virulence factor production, DsbA is a target of interest for anti-virulence strategies and small-molecule inhibitors have been explored.