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Even though the exact mechanism for NssR sensing remains elusive, it
has been suggested that iron is required for the interaction of NssRwith NO
or for the repair of NssR following interaction with NO. Indeed, in other
members of the Fnr family, the presence of a 4Fe-4S group has been impli-
cated in the NO response ( Korner et al., 2003 ), although NssR lacks the
cysteine signature for binding the cluster ( Monk et al., 2008 ).
7.3. Structural modelling of NssR
To facilitate the development of hypotheses for the NssRmechanism, struc-
tural modelling was performed using the online RaptorX server ( Kallberg
et al., 2012; Peng & Xu, 2011 ). This highlights structural homology
between NssR and transcriptional regulators that bind cyclic nucleotides,
haem and
-ketoglutarate; of special interest are catabolite activator protein
from Thermus thermophilus (top hit, 2EV0), CooA from Carboxydothermus
hydrogenoformans (binds haem, 2FMY) and NtcA from Synechococcus elongatus
(a global nitrogen regulator, 2XGX). Although RaptorX predicts structural
homology between NssR- and cAMP-binding proteins ( Fig. 4.7 A), the
most obvious candidate to occupy the ligand-binding cleft is haem, given
the requirement of iron for NssR activity in vivo ( Monk et al., 2008 ) and
the involvement of this cofactor in NO- and CO-sensing by the bacterial
transcription factors DNR ( Giardina et al., 2008 ) and CooA ( Nakajima
et al., 2001 ). Indeed, a histidine residue, a common haem ligand, is predicted
in the vicinity of the ligand-binding cleft ( Fig. 4.7 B). Given that NssR only
a
Figure 4.7 Structural modelling of the transcriptional regulator NssR. (A) Catabolite acti-
vator protein (PDB id¼4EV0) was used as a structural template for NssR. cAMP is shown
bound to each monomer. (B) The C99 and H56 side chains are shown in the apoprotein
dimer.
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