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and the GxGxxP motif for NADH binding are mutated in Type II flavoHbs.
Additionally, an RKY/F sequence motif, known as a high-affinity lipid-
binding site (
Hunte, 2005
) appears conserved within the proximal site of
haem in Type II flavoHbs, suggesting the possibility of its strong association
with membrane lipids. Interestingly, a co-factor binding site, resembling the
FAD-binding motif of respiratory lactate dehydrogenase, has been found in
flavoHb of
M. tuberculosis
(
Gupta et al., 2012
). Interestingly, this FAD-
binding motif is conserved in Type II flavoHbs of pathogenic Mycobacteria,
whereas in many flavoHbs of non-pathogenic Mycobacteria and certain
actinomycetes, these FAD-binding motifs are not fully conserved. These
unusual features suggest that the structural and functional properties of
co-factor-binding domains of type II flavoHbs are different from other
microbial flavoHbs.
4.2. Functional properties
Not much investigation has been done on the flavoHbs of Mycobacteria and
only primary information on the flavoHb of
M. tuberculosis
is available
(
Gupta et al., 2012, 2011
). Close similarity of Type I flavoHbs of
Mycobacteria with other microbial flavoHbs indicates that they may be
structurally and functionally similar. Type II flavoHb of
M. tuberculosis
(MtbFHb) is a monomeric protein of 43 kDa that has been found closely
associated with the cell membrane (
Gupta et al., 2012
). At variance with
conventional flavoHbs that display the pentacoordinated high-spin form,
MtbFHb unusually displays the hexa-coordinated form in both ferric and
ferrous states, indicating that it may not be able to carry out the NOD reac-
tion similar to other flavoHbs. Consistent with this, experimental studies
confirmed that MtbFHb lacks this activity. Instead, it was found to confer
resistance against oxidative stress through a novel electron transfer mecha-
nism via consumption of
D
-lactate that may accumulate during membrane
lipid peroxidation (
Gupta et al., 2011
). In the absence of information on
other Mycobacterial flavoHbs, the physiological function of this new class
of flavoHbs cannot be generalised. Further studies are required to under-
stand the precise role of MtbFHb in electron transfer and the oxidative stress
response of Mycobacteria.
4.3. Genomic organisation and genetic regulation
Genomic organisation of Type I and Type II flavoHbs has been obtained
from the available Mycobacteria genome data. The flanking genes of Type
