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not extending its effects to the partner subunit of the dimer. However, it
cannot be excluded that the quaternary structure modulates protein affinity
for CO by affecting the tertiary structure of the monomers. Recent molec-
ular dynamics investigations have shown that dimerisation has profound
consequences on the structure and the dynamics of
Ma
Pgb
*
(
Forti
et al., 2011
). Thus, a mechanism of homotropic allosteric control of affinity
for CO appears to be operative in
Ma
Pgb
*
, where changes in rate constants
for CO binding to and dissociation from the haem upon ligation/
deligation may bear consequences for a yet unknown reaction, sequentially
involving two substrates.
The recent structures of
Ma
Pgb
*
in complex with different ligands
allowed to propose a stereochemical mechanism which could be at the basis
of the conformational switching between the
Ma
Pgb
*
r
t
and
Ma
Pgb
*
states.
According to such mechanism, Phe(93)E11 residue could sense the presence
of a haem-bound ligand through its steric hindrance. Information on the
liganded state would then be transferred to Trp(60)B9, which would
re-arrange its side chain enabling a hydrogen bond to the haem-bound
ligand and the concomitant closing of tunnel 1. The presence of more than
one residue, namely Trp(60)B9 and Tyr(61)B10, involved in hydrogen
bond interactions with the haem-bound ligand, and the conformational
flexibility of the distal site residues, which can modulate hydrogen bond
strength, may explain the observed heterogeneity in resonance Raman
stretching bands and in the CO dissociation kinetics. Conversely, the struc-
tural bases for the heterogeneous ligand-binding kinetics remain unclear,
although the effects exerted by the haem-proximal site residues as well as
by other residues along the tunnel pathways may be relevant.
Besides the putative involvement of
Ma
Pgb in CO metabolism, very
recently, kinetics and thermodynamics of ferric and ferrous
Ma
Pgb
nitrosylation have shown that addition of NO to the ferric protein leads
to the transient formation of the
Ma
Pgb(III)-NO complex in equilibrium
with
Ma
Pgb(II)-NO
þ
. In turn,
Ma
Pgb(II)-NO
þ
is converted to
Ma
Pgb(II)
by OH
-based catalysis. Then,
Ma
Pgb(II) binds NO very rapidly leading to
the formation of the
Ma
Pgb(II)-NO complex. The rate-limiting step for
reductive nitrosylation of
Ma
Pgb(III) is represented by the OH
-mediated
reduction of
Ma
Pgb(II)-NO
þ
to
Ma
Pgb(II) (
Ascenzi et al., 2013
). These
results suggest a potential role of
Ma
Pgb in scavenging of reactive nitrogen
and oxygen species, which appears pivotal in the physiology of the strictly
anaerobic
M
.
acetivorans
. In fact, multiple functional roles can be envisaged
for
Ma
Pgb, as its scavenging function(s) might co-exist with enzymatic
