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Arsenate reductase from S. aureus plasmid pI258 is a phosphatase drafted for redox duty

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Abstract

Arsenate reductase (ArsC) from Staphylococcus aureus plasmid pI258 plays a role in bacterial heavy metal resistance and catalyzes the reduction of arsenate 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 tyrosine phosphatases (LMW PTPases). Remarkably, kinetic experiments show that 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 pre-existing catalytic site and that its evolutionary origin is different from those of arsenate reductases from Escherichia coli plasmid R773 and from Saccharomyces cerevisiae. The mechanism proposed here for the catalysis of arsenate reduction by pI258 ArsC involves a nucleophilic attack by Cys 10 on arsenate, the formation of a covalent intermediate and the transport of oxidative equivalents by a disulfide cascade. The reaction is associated with major structural changes in the ArsC.

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Figure 1: The structure of pI258 ArsC.
Figure 2: Parallel evolution of arsenate reductases.
Figure 3: Catalytic mechanism of pI258 ArsC.

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Acknowledgements

We wish to thank R. Loris and D. Maes for help with data collection, K. Van Belle for the purification of the SeMet ArsC and A. Desmyter for the construction of the C89L mutant of pI258 ArsC. We are also grateful to P. Tucker for help with the MAD datacollection and Y. Geunes for help with figures. We thank S. Silver of the University of Illinois College of Medicine, Chicago, for providing us with the arsC gene of plasmid pI258. We thank the ESA program Prodex for funding for the study of crystallization processes. This work was funded in part by the VIB, Vlaams Interuniversitair instituut voor Biotechnologie and the Fund for Scientific Research Flanders (F.W.O.) (Belgium) and the Research Council of the VUB. J.C.M. is a Postdoctoral Fellow of the F.W.O.

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  1. Dienst Ultrastruktuur, Vlaams interuniversitair Instituut voor Biotechnologie (VIB), Vrije Universiteit Brussel, Paardenstraat 65, St. Genesius Rode, B-1640, Belgium

    Ingrid Zegers, José C. Martins, Lode Wyns & Joris Messens

  2. High Resolution NMR Centre, Vrije Universiteit Brussel, Pleinlaan 2, B-1050, Brussels, Belgium

    José C. Martins & Rudolph Willem

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  1. Ingrid Zegers
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  2. José C. Martins
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Correspondence to Ingrid Zegers.

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Zegers, I., Martins, J., Willem, R. et al. Arsenate reductase from S. aureus plasmid pI258 is a phosphatase drafted for redox duty. Nat Struct Mol Biol 8, 843–847 (2001). https://doi.org/10.1038/nsb1001-843

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