Ascaris haemoglobin is a nitric oxide-activated 'deoxygenase'

被引:177
作者
Minning, DM
Gow, AJ
Bonaventura, J
Braun, R
Dewhirst, M
Goldberg, DE
Stamler, JS [1 ]
机构
[1] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA
[2] Duke Univ, Med Ctr, Howard Hughes Med Inst, Durham, NC 27710 USA
[3] Duke Univ, Med Ctr, Dept Cell Biol, Durham, NC 27710 USA
[4] Washington Univ, Sch Med, Howard Hughes Med Inst, Dep Mol Microbiol & Med, St Louis, MO 63110 USA
[5] Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA
[6] Duke Marine Biomed Ctr, Nicholas Sch Environm, Pivers Isl, NC 28516 USA
关键词
D O I
10.1038/46822
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The parasitic nematode Ascaris lumbricoides infects one billion people worldwide. Its perienteric fluid contains an octameric haemoglobin(1-3) that binds oxygen nearly 25,000 times more tightly than does human haemoglobin(4,5). Despite numerous investigations, the biological function of this molecule 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 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.
引用
收藏
页码:497 / 502
页数:6
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