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Figure 5.2 Structure-based sequence alignment of group II (trHbO) haemoglobins of
Mycobacteria.
of the wild type showed the presence of an unusual O-O stretching mode,
suggesting an atypical distal haem pocket, which is rigid and polar and sig-
nificantly different to that in trHbN (
Mukai et al., 2002
). In TyrCD1Phe,
the O-O stretching mode disappeared, suggesting that this residue is impor-
tant in the unique structure of the haem pocket. In wild-type protein, when
CO is bound to the haem, TyrCD1 appears to be forming hydrogen bonds
with the haem-bound CO and the authors postulate that a hydrogen bond is
also formed between TyrCD1 and TyrB10, contributing to the rigidity of
this region of the protein (
Mukai et al., 2002
). The crystal structure of
cyano-met Mtb trHbO showed that the protein exists as a compact dode-
camer with a covalent bond linking TyrB10 to TyrCD1 in the haem distal
cavity (
Milani, Savard, et al., 2003
). A study using UV-enhanced Resonance
Raman spectroscopy confirmed that TrpG8 is involved in stabilising the
ligand upon binding due to a conformational change upon ligation of the
ligand, in concert with TyrB10 and TyrCD1, residues to which TrpG8
forms hydrogen bonds (
Ouellet et al., 2003
). TyrCD1 is also thought to
be involved in the modulation of O
2
binding to the haem of trHbO
(
Ouellet et al., 2003
). The protein fold is conserved, with some modifica-
tions, including a pre-F region which is pushed away from the haem and the
protein core due to a number of insertions and might be reflected in a shift of
the haem group, at some points greater than 7
˚
, in relation to its position in
trHbN. In addition, the haem group is located closer to the surface than in
other trHbs, which could reflect the functional role of trHbO (
Milani,
Savard, et al., 2003
). Another paper showed, using Resonance Raman spec-
troscopy, that CO bound to haem was stabilised by both TyrCD1 and
TrpG8 residues, via hydrogen bonds; in addition, the TrpG8 residue also
anchors TyrCD1 and LeuE11, stabilising the ligand bound to the haem
via hydrogen bonds (
Guallar, Lu, Borrelli, Egawa, & Yeh, 2009
). Other
authors suggest that these hydrogen bonds may represent a considerable bar-
rier to ligand movement towards and away from the haem and may result in
