Globins, such as hemoglobin (Hb) and myoglobin (Mb), have gained attention for their ability to reduce nitrite (NO2-) to nitric oxide (NO). The molecular interactions that regulate this chemistry are not fully elucidated, therefore we address this issue by investigating one part of the active site that may control this reaction. Here, the effects of the 2,4-heme substituents on the nitrite reductase (NiR) reaction, and on the structures and energies of the ferrous nitrite intermediates, are investigated using Mb as a model system. This is accomplished by studying Mbs with hemes that have different 2,4-R groups, namely diacetyldeuteroMb (-acetyl), protoMb (wild-type (wt) Mb, -vinyl), deuteroMb (-H), and mesoMb (-ethyl). While trends on the natural charge on Fe and O-atom of bound nitrite are observed among the series of Mbs, the FeII-NPyr (Pyr = pyrrole) and FeII-NHis93 (His = histidine) bond lengths do not significantly change. Kinetic analysis shows increasing NiR activity as follows: diacetyldeuteroMb < wt Mb < deuteroMb < mesoMb. Nitrite binding energy calculations of the different MbII-nitrite conformations demonstrate the N-bound complexes to be more stable than the O-bound complexes for all the different types of heme structures, with diacetyldeuteroMb having the greatest nitrite binding affinity. Spectral deconvolution on the final product generated from the reaction between MbII and NO2- for the reconstituted Mbs indicates the formation of 1:1 MbIII and MbII-NO. The electronic changes induced by the -R groups on the 2,4-positions do not alter the stoichiometric ratio of the products, resembling wt Mb.
All Science Journal Classification (ASJC) codes
- Inorganic Chemistry