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| Biomolecular Research | Natural Product Research | Computational and Biofunctional Research |
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Computational and Biofunctional Research
Oct.2007
Research Summary
After the completion of the human genome project in 2003, the functions of gene products RNA and proteins as well as metabolites have been investigated as post-genome research. The state-of-the-art technologies in the post-genome sciences are expected to lead to the creation of new industrial fields such as environmental remediation, food production, and novel substances production by improving microbial and plant functions as well as genomic drug discovery, and regenerative therapy. Thus, races to realize them are already underway worldwide. To obtain profound understandings of biological phenomena, we are studying ligand-receptor molecular recognition mechanisms and receptor signal transduction mechanisms on the basis of receptor structures. Regarding receptor studies, we are investigating membrane-bound receptor proteins using crystallographic analysis, fluorescence microscopic analysis, and the combination of photoaffinity labeling and mass spectroscopy, and applying methods in gene technology and computer modeling in the field of bioorganic science . The investigation of the mechanism for functional signal transduction will open a new research field for the scientific elucidation of the mechanisms of signal transduction in organisms. This development and application of sciences and technologies will respond to a high social need for the creation of “a sound society of health and longevity”. Presently, we have been focusing on the elucidation of human function of taste information, development of taste biosensors, new gustatory substances, and healthful food materials.
Major Research Projects
1）Studies on Ligand-Protein Interactions
We have long been engaged in research into the visual pigment Rhodopsin, a G protein-coupled receptor (GPCR), in cooperation with laboratories within our institute and outside. We have constructed a signal transduction model in which GPCRs exhibit dynamic structural changes upon binding of bioactive ligands, by applying a computer modeling technique. On the other hand, we have demonstrated the utility of ligand binding site analysis using photoaffinity labeling and mass spectroscopy in combination, as a tool for elucidating the binding sites and modes of albumin and drugs. We are currently applying this approach to investigations of receptor-ligand interactions in the field of medicinal chemistry and functional food materials.
- Crystal Structure of Squid Rhodopsin with Intracellularly Extended Cytoplasmic Region. Shimamura, T., Hiraki, K., Takahashi, N., Hori, T., Ago, H., Masuda, K., Takio, K., Ishiguro, M., and Miyano, M. J. Biol. Chem., 283 (26), 17753-17756 (2008)
2）Analysis and Application of Molecular Events in Taste
We have been investigating the mechanisms of molecular recognition and signal transduction of bitterness, sweetness, and umami molecules in their receptor proteins (GPCR) by utilizing the basic methods for the elucidation of the receptor-ligand interactions in the molecular structural studies of tastes. In cooperation with the University of Tokyo and Kyoto University, we are developing taste biosensors based on gene technology or cell engineering, with the aim of creating new gustatory substances.
- Microbial Production of Sensory-active Miraculin. Ito, K., Asakura, T., Morita, Y., Nakajima, K., Koizumi, A., Shimizu-Ibuka, A., Masuda, K., Ishiguro, M., Terada, T., Maruyama, J., Kitamoto, K., Misaka, T., and Abe, K. Biochem. Biophys. Res. Comm., 360, 407-411 (2007)
3）Studies on the Function of Water
As a potential research in the field of water functions, we have been focusing on the interactions between biopolymers and water molecules. Presently investigating the functional roles of water molecules with biopolymers capable of retaining large amounts of water molecules, we are endeavoring to build a foundation for elucidating the relationship between living organisms and water in chemical and biological ways, and to bring the findings into industrial applications.
- Microstructure of Poly(γ-gltamic acid) Produced by Bacillus subtilis Consisting of Clusters of d- and l-Glutamic Acid Repeating Units. Wang F., Ishiguro M., Mutsukado M., Fujita K., and Tanaka T. J. Agric. Food Chem., 56 (11), 4225-4228 (2008)
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