Arsenate reductase (ArsC) from Staphylococcus aureus plasmid pI258 plays a
role in bacterial heavy metal resistance and catalyzes the reduction of ars
enate to arsenite. The structures of the oxidized and reduced forms of ArsC
were solved. ArsC has the PTPase I fold typical for low molecular weight t
yrosine phosphatases (LMW PTPases). Remarkably, kinetic experiments show th
at pI258 ArsC also catalyzes the tyrosine phosphatase reaction in addition
to arsenate reduction. These results provide evidence that ArsC from pI258
evolved from LMW PTPase by the grafting of a redox function onto a preexist
ing catalytic site and that its evolutionary origin is different from those
of arsenate reductases from Escherichia coli plasmid R773 and from Sacchar
omyces cerevisiae. The mechanism proposed here for the catalysis of arsenat
e reduction by pI258 ArsC involves a nucleophilic attack by Cys 10 on arsen
ate, the formation of a covalent intermediate and the transport of oxidativ
e equivalents by a disulfide cascade. The reaction is associated with major
structural changes in the ArsC.