Modulating the nitrite reductase activity of globins by varying the heme substituents: Utilizing myoglobin as a model system.

Modulating the nitrite reductase activity of globins by varying the heme substituents: Utilizing myoglobin as a model system.
J Inorg Biochem. 2015 Oct 22;154:7-20
Authors: Galinato MG, Fogle RS, Stetz A, Galan JF
Abstract
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 Fe(II)-NPyr (Pyr=pyrrole) and Fe(II)-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 Mb(II)-nitrite conformations demonstrate the N-bound complexes to be more stable than the O-bound complexes for all the differe...

Source: Journal of Inorganic Biochemistry - October 22, 2015 Category: Biochemistry Authors: Galinato MG, Fogle RS, Stetz A, Galan JF Tags: J Inorg Biochem Source Type: research