Biology Reference
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studies, seem to confirm the role of the FG-loop in signal transduction
(
Hiruma, Kikuchi, Tanaka, Shiro, & Mizutani, 2007; Reynolds et al.,
2009
). Another important amino acid for signal transduction is Arg214. This
residue is responsible for rigidifying the haem-moiety when a ligand is pre-
sent. It has been suggested that this loss of flexibility might be important for
down regulating the kinase activity (
Tanaka, Nakamura, Shiro, &
Fujii, 2006
).
The second well-characterized FixL comes from the bacterium
B. japonicum
(
Bj
FixL), whose activity is inversely proportional to O
2
depri-
vation (
Sciotti, Chanfon, Hennecke, & Fischer, 2003
). As soon as
Bj
FixL
was identified, it was clear that its functions were not limited to the
nif
genes
expression stimulation in the absence of O
2
. In fact, FixLJ mutants of
B. japonicum
were not able to grow anaerobically, thus suggesting an
involvement also in anaerobic metabolism (
Anthamatten & Hennecke,
1991; Anthamatten et al., 1992
), for example, expression of genes for haem
biosynthesis and/or nitrate and nitrite respiration (
Mesa, Bedmar, Chanfon,
Hennecke, & Fischer, 2003; Nellen-Anthamatten et al., 1998; Page &
Guerinot, 1995; Robles, Sanchez, Bonnard, Delgado, & Bedmar, 2006
).
Bj
FixL crystal structure has been determined in the presence of different
ligands (CN
and CO) that help understanding its ligand-binding mecha-
nism. Notably, in the O
2
-
Bj
FixL, the hydrogen-bonding networks at the
haem distal side (in particular, the ones involving Fe-O
2
and the distal res-
idue Arg220-propionate 7) are crucial for the optimal ligand binding and
recognition and for the signal transduction via the FG-loop rearrangements
(
Balland et al., 2006; Gong, Hao, & Chan, 2000; Hao, Isaza, Arndt, Soltis, &
Chan, 2002
).
In signal transduction, the PAS and the kinase domain act as a unity in
which the kinase inactive form is energetically favourable and the liganded
haem shifts this equilibrium even further (
Ayers & Moffat, 2008; Balland
et al., 2005; Dunham et al., 2003
). Only two forms are present, the active
unliganded form and the inactive O
2
-bound form, which can convert one
into the other in less than 1
m
s(
Key, Srajer, Pahl, & Moffat, 2007
).
Nonetheless, an interesting effect of O
2
trapping has been reported
(
Kruglik et al., 2007
) in which Arg220 rigidifies the haem group, thus
imposing a specific configuration also to the bound O
2
. This constraint,
in combination with the hydrophobicity and structural properties of the
haem distal cavity, creates an O
2
cage that traps the dissociated ligand in
place. This finding might be related to the O
2
-binding memory hypothesis
proposed by Sousa and colleagues in order to explain the non-linear kinase
