| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 1317641 | Journal of Inorganic Biochemistry | 2006 | 9 Pages |
Distantly related members of the hemoglobin (Hb) superfamily including red blood cell Hb, muscle myoglobin (Mb) and the microbial flavohemoglobin (flavoHb) dioxygenate nitric oxide (NO). The reaction serves important roles in NO metabolism and detoxification throughout the aerobic biosphere. Analysis of the stoichiometric product nitrate shows greater than 99% double O-atom incorporation from Hb18O2, Mb18O2 and flavoHb18O2 demonstrating a conserved high fidelity NO dioxygenation mechanism. Whereas, reactions of NO with the structurally unrelated Turbo cornutus MbO2 or free superoxide radical (-O2) yield sub-stoichiometric nitrate showing low fidelity O-atom incorporation. These and other results support a NO dioxygenation mechanism involving (1) rapid reaction of NO with a FeIII-O2 intermediate to form FeIII−OONO and (2) rapid isomerization of the FeIII−OONO intermediate to form nitrate. A sub-microsecond isomerization event is hypothesized in which the O–O bond homolyzes to form a protein caged [FeIVO NO2] intermediate and ferryl oxygen attacks NO2 to form nitrate. Hb functions as a NO dioxygenase by controlling O2 binding and electrochemistry, guiding NO diffusion and reaction, and shielding highly reactive intermediates from solvent water and biomolecules.
