WHY IS DSBA SUCH AN OXIDIZING DISULFIDE CATALYST

DsbA, a member of the thioredoxin family of disulfide oxidoreductases, acts in catalyzing disulfide bond formation by donating its disulfide to newly translocated proteins. We have found that the two central re sidues within the active site Cys-30-Pro-31-His-32-Cys-33 motif are cr itical in determining the exceptional oxidizing power of DsbA. Mutatio ns that change these two residues can alter the equilibrium oxidation potential of DsbA by more than 1000-fold. A quantitative explanation f or the very high redox potential of DsbA was found by measuring the pK (a) of a single residue, Cys-30. The pK(a) of Cys-80 varied dramatical ly from mutant to mutant and could accurately predict the oxidizing po wer of each DsbA mutant protein.