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Letters to Nature

Nature 401, 497-502 (30 September 1999) | doi:10.1038/46822; Received 25 February 1999; Accepted 2 August 1999

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Ascaris haemoglobin is a nitric oxide-activated 'deoxygenase'

Dena M. Minning1,2, Andrew J. Gow1,3, Joseph Bonaventura4, Rod Braun3, Mark Dewhirst3, Daniel E. Goldberg2 & Jonathan S. Stamler3,4,6

  1. Howard Hughes Medical Institute, Departments of Molecular Microbiology and Medicine, Washington University School of Medicine, St Louis, Missouri 63110 , USA
  2. Howard Hughes Medical Institute,
  3. Department of Medicine and
  4. Department of Cell Biology, Duke University Medical Center, Durham, North Carolina 27710, USA
  5. Nicholas School of the Environment, Duke Marine Biomedical Center , Pivers Island, North Carolina 28516, USA
  6. These authors contributed equally to this work.

Correspondence to: Jonathan S. Stamler3,4,6 Correspondence and requests for materials should be addressed to J.S.S. (e-mail: STAML001@mc.duke.edu).

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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.

  1. Howard Hughes Medical Institute, Departments of Molecular Microbiology and Medicine, Washington University School of Medicine, St Louis, Missouri 63110 , USA
  2. Howard Hughes Medical Institute,
  3. Department of Medicine and
  4. Department of Cell Biology, Duke University Medical Center, Durham, North Carolina 27710, USA
  5. Nicholas School of the Environment, Duke Marine Biomedical Center , Pivers Island, North Carolina 28516, USA
  6. These authors contributed equally to this work.

Correspondence to: Jonathan S. Stamler3,4,6 Correspondence and requests for materials should be addressed to J.S.S. (e-mail: STAML001@mc.duke.edu).