Biology Reference
In-Depth Information
for cyclic di-GMP signalling in
Escherichia coli
(
Tuckerman et al., 2009
). As the
DGC activity of YddV (DosC) is lower compared with the PDE activity of
Ec
Dos, the formation of cyclic di-GMP by YddV (DosC) is the rate-
determining step in the YddV (DosC)/
Ec
Dos system. The DGC activity of
YddV (DosC) from
E. coli
is observed in the ferric (0.066 min
1
), O
2
-bound
(0.022 min
1
), and CO-bound forms (0.022 min
1
), while the ferrous and
NO-bound forms show no significant activity (
Kitanishi et al., 2010
). Though
resonance Raman studies suggest that Tyr43 forms the hydrogen bond with
both O
2
and CO, detail mechanisms for ligand discrimination remain to be
elucidated (
Kitanishi et al., 2010
).
There is also an intermolecular system in which the DGC activity is regu-
lated by a separate haem-containing sensor protein such as bacterial H-NOX
domains. H-NOX consists of seven
a
-helices and a four-stranded antiparallel
b
-sheet. Ahaemis sandwiched between a small
a
-helical subdomain at its distal
side and a largemixed-
a
/
b
subdomainat its proximal side.Thehaemis tethered
by His103 (numbering for H-NOX from
Shewanella oneidensis
)(
Erbil, Price,
Wemmer, & Marletta, 2009; Karow et al., 2004; Nioche et al., 2004; Olea,
Boon, Pellicena, Kuriyan, & Marletta, 2008; Olea, Herzik, Kuriyan, &
Marletta, 2010
). The haem propionate shows hydrogen-bonding interaction
with Tyr131, Ser133, and Arg135 that form an “YxSxR” motif (
Karow
et al., 2004; Nioche et al., 2004
). These structural features including an
“YxSxR” motif are conserved among H-NOX domains.
Stand-alone H-NOX domains are most often found in a predicted
operon with a histidine kinase, a receiver domain/protein of a two-
component system, a DGC containing a GGDEF domain, a phosphatase,
or a cyclic diguanylate phosphodiesterases (
Iyer, Anantharaman, &
Aravind, 2003
). The gene encoding
Lp
H-NOX1 in
Legionella pneumophila
is adjacent to a gene encoding a GGDEF-EAL protein (Lpg1057) that shows
DGC activity
in vitro
(
Carlson, Vance, &Marletta, 2010
).
Lp
H-NOX1 con-
tains a b-type haem that can bind NO, but not O
2
(
Boon et al., 2006;
Carlson et al., 2010
). Upon reaction with NO,
Lp
H-NOX1 forms a
5-coorinated nitrosyl haem. NO-bound
Lp
H-NOX1(Fe
2
þ
-NO) inhibits
the DGC activity of Lpg1057 by about 20%, while an external ligand-free
Lp
H-NOX1(Fe
2
þ
) does not (
Carlson et al., 2010
). Though complete inhi-
bition by
Lp
H-NOX1(Fe
2
þ
-NO) is not observed
in vitro
, deletion of the
h-nox 1
gene results in a hyper-biofilm phenotype that shows 40%more bio-
film production than the wild type. This phenotype is caused by a lack of
inhibition of the DGC activity of Lpg1057 by
Lp
H-NOX1 because increas-
ing concentrations of cyclic di-GMP, a second messenger produced by
