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Peroxynitrite reductase activity of bacterial peroxiredoxins

Nature volume 407, pages 211215 (14 September 2000) | Download Citation

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Abstract

Nitric oxide (NO) is present in soil and air, and is produced by bacteria, animals and plants. Superoxide (O-2) arises in all organisms inhabiting aerobic environments. Thus, many organisms are likely to encounter peroxynitrite (OONO-), a product of NO and O -2 that forms at near diffusion-limited rates, and rapidly decomposes upon protonation through isomerization to nitrate (NO- 3; ref. 1) while generating hydroxyl radical (.OH) and nitrogen dioxide radical (.NO 2) (refs 2, 3), both more reactive than peroxynitrite's precursors. The oxidative, inflammatory, mutagenic and cytotoxic potential (ref. 4) of peroxynitrite contrasts with the anti-oxidant, anti-inflammatory and tissue-protective properties ascribed to NO itself5. Thus, the ability of cells to cope with peroxynitrite is central in determining the biological consequences of NO production. We considered whether cells might be equipped with enzymes to detoxify peroxynitrite. Peroxiredoxins have been identified in most genomes sequenced, but their functions are only partly understood. Here we show that the peroxiredoxin alkylhydroperoxide reductase subunit C (AhpC) from Salmonella typhimurium catalytically detoxifies peroxynitrite to nitrite fast enough to forestall the oxidation of bystander molecules such as DNA. Results are similar with peroxiredoxins from Mycobacterium tuberculosis and Helicobacter pylori. Thus, peroxynitrite reductase activity may be widespread among bacterial genera.

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Acknowledgements

We thank L. Chen for generating ahpC mutations, G. St John for the H. pylori clone, H. Erdjument-Bromage and P. Tempst for protein sequencing and T. Sakmar for access to his stopped-flow spectrophotometer. This work was supported by a Norman and Rosita Winston fellowship (R.B.) and by an NIH grant (C.N.).

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  1. *Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, New York 10021, USA

    • Ruslana Bryk
    •  & Carl Nathan
  2. †Basic Chemistry Analytical Support, Merck Research Laboratories, Rahway, New Jersey 07065, USA

    • Patrick Griffin

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Correspondence to Carl Nathan.

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https://doi.org/10.1038/35025109

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