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Ascaris haemoglobin is a nitric oxide-activated ‘deoxygenase’

Nature volume 401, pages 497–502 (1999)Cite this article

Abstract

The parasitic nematode Ascaris lumbricoides infects one billion people worldwide. Its perienteric fluid contains an octameric haemoglobin1,2,3 that binds oxygen nearly 25,000 times more tightly than does human haemoglobin4,5. Despite numerous investigations, the biological function of this molecule has remained elusive. The distal haem pocket contains a metal, oxygen and thiol6, all of which are known to be reactive with nitric oxide. Here we show that Ascaris haemoglobin enzymatically consumes oxygen in a reaction driven by nitric oxide, thus keeping the perienteric fluid hypoxic. The mechanism of this reaction involves unprecedented chemistry of a haem group, a thiol and nitric oxide. We propose that Ascaris haemoglobin functions as a ‘deoxygenase’, using nitric oxide to detoxify oxygen. The structural and functional adaptations of Ascaris haemoglobin suggest that the molecular evolution of haemoglobin can be rationalized by its nitric oxide related functions.

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Figure 1: Interaction of native Ascaris haemoglobin (AH) with NO.
Figure 2: Consumption of NO by Ascaris haemoglobin.
Figure 3: Oxygen consumption by Ascaris haemoglobin.
Figure 4: Analyses of fresh Ascaris worms and related evolutionary implications.

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Acknowledgements

We thank I. Fridovich, A. Hausladen, J. Lanzen and D. Hess for assistance and discussion. This work was supported by the NIH and the ALS association. D.E.G. is the recipient of a Burroughs Wellcome Fund scholar award in molecular parasitology.

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Author notes

  1. Dena M. Minning, Daniel E. Goldberg and Jonathan S. Stamler: These authors contributed equally to this work.

Authors and Affiliations

  1. Howard Hughes Medical Institute Departments of Molecular Microbiology and Medicine, Washington University School of Medicine, St Louis, 63110 , Missouri, USA

    Dena M. Minning & Andrew J. Gow

  2. Howard Hughes Medical Institute, ,

    Jonathan S. Stamler

  3. Department of Medicine,

    Andrew J. Gow, Rod Braun, Mark Dewhirst & Jonathan S. Stamler

  4. Department of Cell Biology, Duke University Medical Center, Durham, 27710, North Carolina, USA

    Joseph Bonaventura & Jonathan S. Stamler

  5. Nicholas School of the Environment, Duke Marine Biomedical Center , Pivers Island, 28516, North Carolina, USA

    Joseph Bonaventura

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Minning, D., Gow, A., Bonaventura, J. et al. Ascaris haemoglobin is a nitric oxide-activated ‘deoxygenase’ . Nature 401, 497–502 (1999). https://doi.org/10.1038/46822

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