Ascaris haemoglobin is a nitric oxide-activated 'deoxygenase'

Dena M. Minning, Andrew J. Gow, Joseph Bonavetura, Rod Braun, Mark Dewhirst, Daniel E. Goldberg, Jonathan S. Stamler

Research output: Contribution to journalArticle

169 Citations (Scopus)

Abstract

The parasitic nematode Ascaris lumbricoides infects one billion people worldwide. Its perienteric fluid contains an octameric haemoglobin that binds oxygen nearly 25,000 times more tightly than does human haemoglobin. Despite numerous investigations, the biological function of this molecule has remained elusive. The distal haem pocket contains a metal, oxygen and thiol, 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.

Original languageEnglish
Pages (from-to)497-502
Number of pages6
JournalNature
Volume401
Issue number6752
DOIs
Publication statusPublished - 30 Sep 1999
Externally publishedYes

Fingerprint

Nitric Oxide
Oxygen
Hemoglobins
Heme
Sulfhydryl Compounds
Ascaris lumbricoides
Molecular Evolution
Metals
Ascaris haemoglobin

ASJC Scopus subject areas

  • General

Cite this

Minning, D. M., Gow, A. J., Bonavetura, J., Braun, R., Dewhirst, M., Goldberg, D. E., & Stamler, J. S. (1999). Ascaris haemoglobin is a nitric oxide-activated 'deoxygenase'. Nature, 401(6752), 497-502. https://doi.org/10.1038/46822

Ascaris haemoglobin is a nitric oxide-activated 'deoxygenase'. / Minning, Dena M.; Gow, Andrew J.; Bonavetura, Joseph; Braun, Rod; Dewhirst, Mark; Goldberg, Daniel E.; Stamler, Jonathan S.

In: Nature, Vol. 401, No. 6752, 30.09.1999, p. 497-502.

Research output: Contribution to journalArticle

Minning, DM, Gow, AJ, Bonavetura, J, Braun, R, Dewhirst, M, Goldberg, DE & Stamler, JS 1999, 'Ascaris haemoglobin is a nitric oxide-activated 'deoxygenase'', Nature, vol. 401, no. 6752, pp. 497-502. https://doi.org/10.1038/46822
Minning DM, Gow AJ, Bonavetura J, Braun R, Dewhirst M, Goldberg DE et al. Ascaris haemoglobin is a nitric oxide-activated 'deoxygenase'. Nature. 1999 Sep 30;401(6752):497-502. https://doi.org/10.1038/46822
Minning, Dena M. ; Gow, Andrew J. ; Bonavetura, Joseph ; Braun, Rod ; Dewhirst, Mark ; Goldberg, Daniel E. ; Stamler, Jonathan S. / Ascaris haemoglobin is a nitric oxide-activated 'deoxygenase'. In: Nature. 1999 ; Vol. 401, No. 6752. pp. 497-502.
@article{a8f4312f3c624b92b58a8f2b974d78a7,
title = "Ascaris haemoglobin is a nitric oxide-activated 'deoxygenase'",
abstract = "The parasitic nematode Ascaris lumbricoides infects one billion people worldwide. Its perienteric fluid contains an octameric haemoglobin that binds oxygen nearly 25,000 times more tightly than does human haemoglobin. Despite numerous investigations, the biological function of this molecule has remained elusive. The distal haem pocket contains a metal, oxygen and thiol, 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.",
author = "Minning, {Dena M.} and Gow, {Andrew J.} and Joseph Bonavetura and Rod Braun and Mark Dewhirst and Goldberg, {Daniel E.} and Stamler, {Jonathan S.}",
year = "1999",
month = "9",
day = "30",
doi = "10.1038/46822",
language = "English",
volume = "401",
pages = "497--502",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Publishing Group",
number = "6752",

}

TY - JOUR

T1 - Ascaris haemoglobin is a nitric oxide-activated 'deoxygenase'

AU - Minning, Dena M.

AU - Gow, Andrew J.

AU - Bonavetura, Joseph

AU - Braun, Rod

AU - Dewhirst, Mark

AU - Goldberg, Daniel E.

AU - Stamler, Jonathan S.

PY - 1999/9/30

Y1 - 1999/9/30

N2 - The parasitic nematode Ascaris lumbricoides infects one billion people worldwide. Its perienteric fluid contains an octameric haemoglobin that binds oxygen nearly 25,000 times more tightly than does human haemoglobin. Despite numerous investigations, the biological function of this molecule has remained elusive. The distal haem pocket contains a metal, oxygen and thiol, 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.

AB - The parasitic nematode Ascaris lumbricoides infects one billion people worldwide. Its perienteric fluid contains an octameric haemoglobin that binds oxygen nearly 25,000 times more tightly than does human haemoglobin. Despite numerous investigations, the biological function of this molecule has remained elusive. The distal haem pocket contains a metal, oxygen and thiol, 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.

UR - http://www.scopus.com/inward/record.url?scp=0033619223&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033619223&partnerID=8YFLogxK

U2 - 10.1038/46822

DO - 10.1038/46822

M3 - Article

VL - 401

SP - 497

EP - 502

JO - Nature

JF - Nature

SN - 0028-0836

IS - 6752

ER -