The ubiquity of arsenic in the environment has led to the evolution of enzymes for arsenic detoxification. An initial step in arsenic metabolism is the enzymatic reduction of arsenate [As(V)] to arsenite [As(III)] which could be catalyzed in bacteria by arsenate reductases (ArsC) which are members of the Thioredoxin-like protein family. ArsC proteins from different sources have unrelated sequences and structural folds. Arsenate reductase is unusual among well-studied enzyme classes due to the diversity of several independent enzyme families. ArsC from Vibrio cholerae is similar to that encoded by ArsC on the R733 plasmid of Escherichia coli. The purified enzyme exhibits arsenate reductase activity dependent on the presence of reduced glutathione (GSH) and glutaredoxin (Grx). The enzyme uses three separate cysteine residues as it was observed for the thioredoxin-linked enzymes. However, in case of ArsC protein, only one cysteine residue is in the arsenate reductase primary enzyme sequence and the others occur in GSH and Grx.