Biology Reference
In-Depth Information
His119
CO
His119
Fe
3+
Fe
2+
Fe
2+
or
Fe
2+
Cys170
His171
His171
Figure 7.2 Coordination structures of the haem in NPAS2.
the ferric haem in the dominant species of the PAS-A domain. The bHLH-
PAS-A shows different spectroscopic properties from those of the isolated
PAS-A domain (
Mukaiyama et al., 2006; Uchida, Sagami, Shimizu,
Ishimori, & Kitagawa, 2012
). The ferric haem in the bHLH-PAS-A is pro-
posed to consist of His119 and His171 as the axial ligands instead of His119
and Cys170 (
Uchida et al., 2012
). These differences may be caused by an
artificial effect by domain truncation or may suggest the existence of the
equilibrium of the coordination structures between bis-His and Cys-His
coordinations. Though it is proposed that ligand exchange takes place
between Cys170 and His171 upon the change in the oxidation state of
the haem (
Fig. 7.2
), its physiological role is not obvious at present. Upon
CO binding to the haem, another ligand exchange takes place between
the haem-bound His and CO, though it is not known which His is replaced
by CO.
The mutation His119 or His171 to Ala results in remarkable reduced
transcriptional activity, which is caused by impaired heterodimer formation
with BMAL1 (
Ishida, Ueha, & Sagami, 2008
). The C170A variant shows the
same transcriptional activity as the wild type (
Ishida et al., 2008
). These
results suggest that the ligand exchange between the haem-bound His
and CO plays an important role for the functional regulation of NPAS2,
which may cause conformational changes in the haem pocket triggered
by the dissociation of the haem-bound His.
4. TWO-COMPONENT SYSTEMS FOR
TRANSCRIPTIONAL REGULATION
4.1. FixL/FixJ two-component system
Two-component signal transduction system consists of two separate pro-
teins, a sensor kinase and a response regulator, which is one of the most
utilised biological signal transduction systems (
Jung, Fried, Behr, &
Heermann, 2011; Kirby, 2009
). In this system, sequential phosphoryl group
transfer reactions play important role for signal transductions. The sensor
