Biology Reference
In-Depth Information
Figure 8.2 A stereo view of sperm whale Mb (3/3) (pdb:1JP6,
Urayama, Gruner, &
Phillips, 2002
) and B. subtilis TrHbII (HbO) (pdb:1UX8,
Ilari, Giangiacomo, Boffi, &
Chiancone, 2005
) tertiary structures, including the haem group and helices. Modifica-
tions of the conventional 3/3 Mb fold occur particularly at helix A and in the CD-D
regions, which are virtually absent, and in the EF-F regions of TrHbs. A very short seg-
ment linking helices C and E forces the haem-distal helix E very close to the haem distal
side.
of that of ferrous horseradish peroxidase, suggesting that this globin may par-
ticipate in cyanide detoxification (
Bolli et al., 2008
).
Strikingly, TrHbs belonging to group III (or N) host a protein matrix
tunnel system offering a potential path for ligand diffusion to and from
the haem distal site. The apolar tunnel/cavity system, extending for approx-
imately 28
˚
through the protein matrix, is conserved in TrHbs belonging
to group N, although with modulation of its size and/or structure (
Milani
et al., 2001; Pesce, Milani, Nardini, & Bolognesi, 2008
). It has been pro-
posed that in
Mycobacterium tuberculosis
HbN, the haem-Fe/O
2
stereochem-
istry and the protein matrix tunnel may promote O
2
/NO chemistry
in vivo
,
as a
M. tuberculosis
defence mechanism against macrophage nitrosative stress
(
Milani et al., 2001
).
Unlike HbN,
M. tuberculosis
HbO does not host the protein matrix tun-
nel but two topologically equivalent matrix cavities. Moreover, the small
apolar Ala E7 residue leaves room for ligand access to the haem distal site
through the conventional E7 path (
Pesce et al., 2008
), as proposed for Mb.
In contrast to TrHbs I and II (
Milani et al., 2004, 2001; Nardini et al.,
2006; Pesce et al., 2008
), Ctb does not display protein matrix tunnel/cavity
systems at all (
Nardini et al., 2006
). Although the gating role of HisE7 in
the modulation of ligand access into and out of the heam pocket is debated
