Biology Reference
In-Depth Information
peroxide and in macrophages during infection, adding extra proof to the
hypothesis that MtbFHb is part of the
M. tuberculosis
oxidative stress defence
(
Gupta et al., 2012
).
5.3. Redox signalling and stress management
Haem proteins, including Hbs, have been found to play an important role in
sensing gaseous O
2
and other ligands. The interaction between the haem-
Fe-bound ligand and haem distal amino acid residues and/or haem pocket
geometry play a vital role in carrying out distinct redox reactions and signal
triggering. TrHbO of
M. tuberculosis
has been found to have some properties
that identify a possible function as a redox sensor (
Ouellet, Ranguelova,
et al., 2007
). It has been shown that trHbO could be prone to redox reac-
tions due to the presence of oxidisable residues in the haem pocket, for
example, TyrB10, TrpG8 and the unusual Tyr CD1 (
Ouellet,
Ranguelova, et al., 2007
). Optical spectra suggest that Mtb trHbO can react
with hydrogen peroxide and form a novel intermediate, containing ferric
haem iron and two oxidising equivalents, that is similar to the product of
the reaction of peroxidases and other Hbs with high concentrations of
H
2
O
2
, indicating that trHbO may have peroxidase activity. Similar oxida-
tion/reduction function has also been suggested for trHbO of
M. leprae
(
Ascenzi, De Marinis, Coletta, & Visca, 2008; Ascenzi, Milani, et al.,
2006
) and may be true for other group II trHbs of Mycobacteria.
5.4. Other functions
As trHbO appears to have some properties that identify a possible function as
a redox sensor, the reaction of purified protein with H
2
O
2
was investigated.
Optical spectra suggest that Mtb trHbO can react with H
2
O
2
and that it
forms Compound III, a common product of the reaction of peroxidases
and other Hbs with high concentrations of H
2
O
2
(
Ouellet, Ranguelova,
et al., 2007
). Peroxidase activity was also shown. Additional evidence
showed that cross-linked dimers were produced after trHbO was exposed
to only 0.25 molar equivalents, common in haemoproteins that are exposed
to H
2
O
2
due to tyrosine-tyrosine cross-links formed after certain amino acid
residues have become radicals due to the transfer of electrons during the
reaction. Indeed, Mtb trHbO has many tyrosine residues which are available
for potential conversion to tyrosol radicals, and that could be responsible for
this dimerisation (
Ouellet, Ranguelova, et al., 2007
). A function as a perox-
idase has also been suggested for Ml trHbO. Both oxy-ferrous and ferrous-
