Reactivity of glutaredoxins 1, 2, and 3 from Escherichia coli shows that glutaredoxin 2 is the primary hydrogen donor to ArsC-catalyzed arsenate reduction.

In Escherichia coli ArsC catalyzes the reduction of arsenate to arsenite using GSH with glutaredoxin as electron donors. E. coli has three glutaredoxins: 1, 2, and 3, each with a classical -Cys-Pro-Tyr-Cys- active site. Glutaredoxin 2 is the major glutathione disulfide oxidoreductase in E. coli, but its function remains unknown. In this report glutaredoxin 2 is shown to be the most effective hydrogen donor for the reduction of arsenate by ArsC. Analysis of single or double cysteine-to-serine substitutions in the active site of the three glutaredoxins indicated that only the N-terminal cysteine residue is essential for activity. This suggests that, during the catalytic cycle, ArsC forms a mixed disulfide with GSH before being reduced by glutaredoxin to regenerate the active ArsC reductase.