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; encoded by the arsC gene in bacteria) participates to achieve arsenate resistance in both prokaryotes and yeast by reducing arsenate to arsenite; the arsenite is then exported by a specific transporter. The crystal structure of Bacillus subtilis arsenate reductase in the reduced form with a bound sulfate ion in its active site is solved at 1.6-A resolution. Significant structural similarity is seen between arsenate reductase and bovine low molecular weight protein tyrosine phosphatase, despite very low sequence identity. The similarity is especially high between their active sites. It is further confirmed that this structural homology is relevant functionally by showing the phosphatase activity of the arsenate reductase in vitro. Thus, we can understand the arsenate reduction in the light of low molecular weight protein 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 mechanism.
Bennett
M S
MS
Department of Molecular Biophysics, Kemicentrum, P.O. Box 124, Lund University, SE-221 00 Lund, Sweden.
Guan
Z
Z
Laurberg
M
M
Su
X D
XD
D000595:Amino Acid Sequence; D000814:Aniline Compounds / Q000378:metabolism; D000818:Animals; D053502:Arsenate Reductases; D001412:Bacillus subtilis / Q000201:enzymology; D001665:Binding Sites; D002384:Catalysis; D003545:Cysteine / Q000378:metabolism; D006868:Hydrolysis; D008958:Models, Molecular; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009943:Organophosphorus Compounds / Q000378:metabolism; D010084:Oxidation-Reduction; D010088:Oxidoreductases / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology; D017433:Protein Structure, Secondary; D017027:Protein Tyrosine Phosphatases / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity
D000814:Aniline Compounds; D009943:Organophosphorus Compounds; C068798:4-aminophenylphosphate; D010088:Oxidoreductases; D053502:Arsenate Reductases; D017027:Protein Tyrosine Phosphatases; D003545:Cysteine