The Dos Family of Globin-Related Sensors Using PAS Domains to Accommodate Haem Acting as the Active Site for Sensing External Signals - Advances in Microbial Physiology - page 296

is free of hydrogen bonds, another one shows electrostatic and/or hydrogen-
bond interaction within the distal haem pocket ( Ioanoviciu et al., 2007;
Yukl et al., 2007 ). In the resonance Raman spectra of Y171F DosS, these
hydrogen-bonded CO and NO conformers are not observed ( Yukl
et al., 2008 ).
Y171F variant of DosS loses ability of ligand discrimination for CO, NO,
and O 2 . While only the oxy form is inactive for kinase activity in wild-type
DosS, all of CO, NO, and O 2 forms are inactive complexes in the Y171F
variant ( Yukl et al., 2008 ). In contrast, the ferrous form of Y171F DosS
exhibits kinase activity comparable to that of wild type ( Yukl et al.,
2008 ). Yukl et al. (2008) have proposed that interactions between
Tyr171 and distal diatomic ligands turn the kinase activity on or off, and that
mutation of Tyr171 to Phe disrupts the on-off switch, leading to an inactive
kinase in all states.
5. HAEM-CONTAINING PAS FAMILY FOR THE
REGULATION OF DIGUANYLATE CYCLASES
AND PHOSPHODIESTERASES
5.1. Regulation of diguanylate cyclases activity through
interactions between haem and external ligand
Bis-(3 0 ,5 0 )-cyclic dimeric guanosine monophosphate (cyclic di-GMP) is a
ubiquitous bacterial second messenger involved in the regulation of cell
motility, differentiation, development, virulence, biofilm formation, and
factor-stimulated proliferation in human colon cancer cells ( Cotter &
Stibitz, 2007; Jenal, 2004; Jenal & Malone, 2006; Pesavento & Hengge,
2009; R ¨ mling & Amikam, 2006; R ¨ mling, Gomelsky, & Galperin,
2005; Tamayo, Pratt, & Camilli, 2007 ). While different biochemical
processes seem to be controlled by cyclic di-GMP in response to different
extracellular signals, this second messenger generally regulates transitions
between the free-living, motile lifestyle and the sessile lifestyle ( Cotter &
Stibitz, 2007; Jenal, 2004; Jenal & Malone, 2006; Pesavento & Hengge,
2009; R¨mling & Amikam, 2006; R¨mling et al., 2005; Tamayo et al.,
2007 ). Low concentrations of cyclic di-GMP promote motile growth, while
high concentrations promote sessile growth with biofilm formation. The
intracellular concentrations of cyclic di-GMP are controlled by the balance
between synthesis and hydrolysis of cyclic di-GMP, which are catalysed by
the enzymes, diguanylate cyclases (DGCs) and phosphodiesterases (PDEs),
respectively ( Cotter & Stibitz, 2007; Jenal, 2004; Jenal & Malone, 2006;