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Shiloh, 2000; Ohno et al., 2003; Schnappinger, Schoolnik, & Ehrt, 2006;
Visca, Fabozzi, Milani, Bolognesi, & Ascenzi, 2002
). The distinct features
of the haem active site structure of NO-responsive mycobacterial 2/2Hbs
and their ligand-binding properties (
Milani et al., 2001, 2003; Milani,
Pesce, et al., 2004; Milani et al., 2005; Visca, Fabozzi, Milani, et al.,
2002
), combined with co-occurrence of multiple 2/2Hb classes in individ-
ual mycobacterial species and their temporal expression patterns
in vivo
(
Fabozzi, Ascenzi, Renzi, & Visca, 2006; Ouellet et al., 2002, 2003
), suggest
that these globins play different physiological functions (
Ascenzi, Bolognesi,
Milani, Guertin, & Visca, 2007
). For instance,
M. tuberculosis
2/2HbN is
endowed with a potent nitric-oxide dioxygenase activity and has been found
to relieve nitrosative stress (
Couture, Yeh, et al., 1999; Pathania, Navani,
Gardner, et al., 2002
) enhancing
in vivo
survival of a heterologous host,
Sal-
monella enterica typhimurium
, within the macrophages (
Pawaria et al., 2007
).
These findings strongly support the NO scavenging and detoxification roles
of 2/2HbN, which may be vital for
in vivo
survival and pathogenicity of
M. tuberculosis.
Similarly, a
M. bovis
mutant lacking 2/2HbN does not oxi-
dize NO to NO
3
and shows decreased respiration upon exposure to NO
(
Ouellet et al., 2002
). Although to a lesser extent, a similar protective effect
was also reported for
M. smegmatis
2/2HbN in the homologous system
(
Lama, Pawaria, & Dikshit, 2006
).
Detoxification of NO to nitrate is the hypothetical physiological func-
tion proposed also for
T. pyriformis
2/2HbN. Based on oxygen affinity mea-
surements, it has been estimated that
T. pyriformis
2/2HbN within the cell
would be maintained in the Fe(II)-O
2
form, indicating that
T. pyriformis
2/2HbN does not function as an oxygen transporter. In addition, nitrosative
stress mediated by sodium nitroprusside inhibits glyceraldehyde 3-phosphate
dehydrogenase activity in
T. pyriformis
(
Fourrat, Iddar, Valverde, Serrano, &
Soukri, 2007
). Therefore,
T. pyriformis
must have acquired a mechanism that
senses and protects against nitrosative stress conditions, such as NO exposure
(
Igarashi et al., 2011
).
Other widely studiedmembers of the group I 2/2HbNs are cyanobacterial
globins. 2/2HbN from the cyanobacterium
Synechococcus
sp. strain PCC
7002 and PCC 6803 have been characterized structurally and biochemically,
focusing mainly on their two unusual structural properties: the bis-histidyl
coordination of the haem iron in the absence of an exogenous ligand, and
the post-translational covalent attachment of the haem to the globin by
modification of the 2-vinyl substituent (
Falzone et al., 2002; Lecomte
et al., 2004; Lecomte, Vu, & Falzone, 2005; Pond et al., 2012; Scott
