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Trp(60)B9 side chain. Thus, Pgbs maintain the ligand-stabilisation mechanism
based on residue B10, as most invertebrate globins (
Bolognesi et al., 1997
),
but evolved an E7-independent ligand-to-haem path based also on residues
at the B9 and E11 topological positions.
On the basis of the above considerations,
Ma
Pgb has been suggested to be
involved in a ligand-controlled bimolecular process, where loading of the
protein with a first ligand would facilitate ligand binding to the haem cavity
of the second subunit (
Forti et al., 2011
). This hypothesis is in keeping with
experimental findings derived from kinetic studies of CO binding to
Ma
Pgb
*
in solution and gels, which show that the heterogeneous ligand-binding kinet-
ics is affected by ligand concentration, and highlight a ligand-dependent
equilibrium between two conformational species related to fast and slow
CO-rebinding processes in
Ma
Pgb
*
. The putative dual path ligand exchange
mechanism (typical of some enzymes) could bear functional implications for a
yet undiscovered role in
M
.
acetivorans
CO metabolism (
Abbruzzetti et al.,
2012
). At present, the
in vivo
functional role of Pgb is, indeed, an unanswered
and challenging question. The structural flexibility/adaptability of the tertiary
structure, together with its ability to form a quaternary assembly similar to
GCS proteins, strongly suggests that Pgbs may serve several different biological
functions, including protection from nitrosative and oxidative stress, and
formation (together with other GCS proteins) of a common signalling
mechanism addressing diverse physiological functions, such as aerotactic
response. A key test on Pgb function would probably require mutagenesis
in vivo
and analysis of the mutant phenotype. A significant part of future work
on Pgbs is, therefore, expected to derive from microbiology, the results of
which should be integrated with other approaches, such as expression profiles,
biochemical experiments and structural information.
REFERENCES
