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et al., 2003; Ouellet et al., 2003, 2007
). The crystal structure of
M. tuberculosis
2/2HbO has also shown that the simultaneous presence
of Tyr residues at the B10 and CD1 sites may trigger the formation of a
covalent (iso-dityrosine like) bond between the two side chains (
Milani
et al., 2003
), whose functional role is yet unclear.
A similar network of interaction has also been described in
T. fusca
(
Bonamore et al., 2005
) and in
B. subtilis
(
Boechi, Ma˜ez, Luque,
Mart`, & Estrin, 2010; Feis et al., 2008; Giangiacomo et al., 2005
) 2/2HbOs,
where TyrB10, Phe/TyrCD1, and TrpG8 are mainly involved in a
hydrogen-bonding network, thus stabilizing the exogenous ligands. In
T. fusca
2/2HbO, the carbonyl oxygen of the acetate ion ligand is stabilized
by hydrogen bonds with residues TyrCD1 and TrpG8 (
Bonamore et al.,
2005
). When instead a Phe residue is present at the CD1 position, as in
B. subtilis
2/2HbO, TyrB10 assumes the role of hydrogen bond donor
for the interactions with the exogenous ligand (
Giangiacomo et al.,
2005
). GlnE11, TrpG8, and ThrE7 complete the polar distal frame with
GlnE11 side chain and the TrpG8 indolic nitrogen atom at hydrogen bond-
ing distance to the bound ligand (
Giangiacomo et al., 2005
). The
G. stearothermophilus
2/2HbO haem pocket displays a hydrogen bonding
network involving TyrB10 and TrpG8 residues similar to
B. subtilis
2/2HbO (
Ilari et al., 2007
). Interestingly in
M. tuberculosis
2/2HbO, when
TyrCD1 is mutated to Phe, is TyrB10 the hydrogen bonding residue for the
haem-bound ligand (
Ouellet et al., 2003
), thus mimicking in
M. tuberculosis
2/2HbO what has been observed in
B. subtilis
and
G. stearothermophilus
2/2HbOs (
Giangiacomo et al., 2005; Ilari et al., 2007
).
Recently,
B. subtilis
and
T. fusca
, group II 2/2HbOs have been demon-
strated to be able to bind CO in the ferrous state (
Droghetti et al., 2010
),
and sulphide (
Nicoletti et al., 2010
) or fluoride (
Nicoletti et al., 2011
)in
the ferric state. The architecture of the distal cavities of
B. subtilis
and
T. fusca
2/2HbOs can be compared with those of the few reported examples
of sulphide-binding haem proteins (
Rizzi, Wittenberg, Coda, Ascenzi,
& Bolognesi, 1996
). Molecular dynamics simulation indicates that only
TrpG8 residue contributes to the sulphide stabilization through
direct hydrogen-bonding interaction, thus accounting for the relatively
high affinity for sulphide in these proteins (
Nicoletti et al., 2010
).
A. tumefaciens
2/2HbO is the first example of a structure where the
topological position CD1 is occupied by His. Here, the haem distal site is
characterized by the presence of a highly intertwined hydrogen-bonding
network, involving residues TyrB10, HisCD1, SerE7, TrpG8, and three
