The parasitic nematode Ascaris lumbricoides infects one billion people worl
dwide. Its perienteric fluid contains an octameric haemoglobin(1-3) that bi
nds oxygen nearly 25,000 times more tightly than does human haemoglobin(4,5
). Despite numerous investigations, the biological function of this molecul
e has remained elusive. The distal haem pocket contains a metal, oxygen and
thiol(6), 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 mec
hanism 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 f
unctional adaptations of Ascaris haemoglobin suggest that the molecular evo
lution of haemoglobin can be rationalized by its nitric oxide related funct
ions.