Bacillus subtilis arsenate reductase is structurally and functionally similar to low molecular weight protein tyrosine phosphatases

Arsenate is an abundant oxyanion that, because of its ability to mimic the phosphate group, is toxic to cells. Arsenate reductase(EC 1.97.1.5; encoded by the arsC gene in bacteria) participates to achieve arsenate resistance in both prokaryotes and yeast by reducing arsenate to arsenite; the arsenit e is then exported by a specific transporter. The crystal structure of Baci llus subtilis arsenate reductase in the reduced form with a bound sulfate i on in its active site is solved at 1.6-Angstrom resolution. Significant str uctural similarity is seen between arsenate reductase and bovine low molecu lar weight protein tyrosine phosphatase, despite very low sequence identity . The similarity is especially high between their active sites. It is furth er confirmed that this structural homology is relevant functionally by show ing the phosphatase activity of the arsenate reductase in vitro. Thus, we c an understand the arsenate reduction in the light of low molecular weight p rotein tyrosine phosphatase mechanism and also explain the catalytic roles of essential residues such as Cys-10, Cys-82, Cys-89, Arg-16, and Asp-105. A "triple cysteine redox relay" is proposed for the arsenate reduction mech anism.