Okazaki Institute for Integrative Biology

RESEARCH THEMES

As all organism including bacteria, plants, and animals are exposed to various kinds of chemical and physical stimuli in their life, they have the response systems for them to maintain their homeostasis. The regulations of gene expression, metabolism, and motility in response to the external stimuli are typical examples of such systems. In biological system, sensor proteins, which are the component of signal transduction systems, are used to sense the external signals. While many biological signal transduction systems, most of which are constituted by simple proteins without any prosthetic group, have been studying until now, it becomes apparent that there are some biological signal transduction systems that consist of a metalloprotein as a sensor protein.

Our research interest is focused on the structure and function relationships of novel sensor proteins that use a heme as the active site for sensing gas molecules as O2, CO, and NO. The main targets of our research are the CO sensor protein CooA, O2 sensor proteins HemAT and HemDGC. CooA, a member of the CRP/FNR family of transcriptional regulators, regulates the transcription of the target genes in response to CO. HemAT is a signaltransducer protein in the aerotaxis control system in some bacteria and archea. HemDGC is a heme-containing diguanylate cyclase, which catalyzed the formation of a bacterial second messenger, cyclic di-GMP, from GTP. We are elucidating the structure and function of these heme-based sensor proteins by means of biochemical, biophysical, and molecular biological techniques. We are also interested in other metalloproteins that have a novel function and/or structure, the molecular mechanisms of biogenesis of metal-containing prosthetic group and of the homeostasis for transition metal ions in cell.

SELECTED PUBLICATIONS

1. "Spectroscopic and redoxproperties of a CooA homologue from Carboxydothermus hydrogenoformans" J. Biol. Chem. 280, 3269?3274 (2005)
2. "Regulation of aldoxime dehydratase activity by redox dependent change in the coordination structure of the aldoximehemecomplex" J. Biol. Chem. 280, 5486?5490 (2005)
3. "Specific hydrogen bonding networks responsible for selective O2 sensing for the oxygen sensor protein HemAT from Bacillus subtilis" Biochemistry 45, 8301?8307 (2006)
4. "Crystal structure of CO-sensing transcriptional activator CooA bound to exogenous ligand imidazole" J. Mol. Biol. 367, 864?871 (2007)
5. "Metal-containing sensor proteins sensing diatomic gas molecules" Dalton Trans., 3137-3146 (2008)