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Strucure and Function Analysis of Biomolecules(Chemistry)

Inoue TsuyoshiProfessor

I have been with the Graduate School of Pharmaceutical Sciences since November 2018. Until then, I was a member of the Graduate School of Engineering. I have been studying on the research of metal binding proteins by using X-ray crystallography, but after encountering a liquid called MA-T, I became involved in the development of basic technology for Cryo-Electron Microscopy. I am engaged in drug discovery research with the theme of developing new modalities based on the structural biology method.

Research theme

Development of basic techniques for protein structure analysis using cryo-electron microscopy

The reaction mechanism of MA-T (Matching Transformation System), a disinfectant/deodorant, led to the discovery of the methane to methanol transforming reaction, which is one of the dream reactions of the 21st century. We are applying this to graphene surfaces and developing an epoxidized grid (EG-Grid) to automate single-particle structural analysis using CryoEM.

Drug development using antibody engineering

Antibodies with lowered molecular weight are attracting attention as one of the next generation biopharmaceuticals. We are designing highly active antibodies (single chain antibody of diabody) by finding and modifying epitopes using structural biology.

Development of Imaging Technology

A drug delivery system (DDS) is a technology that delivers the desired medicinal component to the site of disease. DDS can be constructed relatively easily using antibodies and is expected to improve therapeutic efficacy and reduce side effects. We are developing a technology to identify the location of cancer located in the deeper part of the body and to treat it at the same time.

Structural Chemistry of Metalloproteins

Metal ions incorporated into proteins in living organisms have various functions. We are conducting research to elucidate the mechanism from the analysis of relationship between structure and function of metalloproteins.

Representative achievements

Ohkubo, K. et al., “Photochemical C–H oxygenation of side-chain methyl groups in polypropylene with chlorine dioxide”, Chemical Communications, 55, 4723-4726(2019).

Fujita, J. et al., “Epoxidized graphene grid for high-throughput high-resolution cryoEM structural analysis”, bioRxiv,11.17.468963(2021).

Maeda, R. et al., “Nanobodies recognizing conserved hidden clefts of all SARS-CoV-2 spike variants”, bioRxiv,10.25.465714(2021).

Kado, Y et al., “Epiregulin recognition mechanisms by anti-epiregulin antibody 9E5: Structural, functional and molecular dynamics simulation analyses”, J. Biol. Chem., 291: 2319-2330 (2016).

Kawato, T. et al., “Structure-based design and synthesis of a bivalent iminobiotin analogue showing strong affinity toward a low immunogenic streptavidin mutant”, Bioscience, Biotechnology, and Biochemistry, 79(4), 640-642 (2015).

Fukuda, Y. et al., “Crystallographic study on dioxygen chemistry in a copper-containing nitrite reductase from Geobacillus thermodenitrificans”, Acta Crystallographica Sect D, 74(8), 769-777 (2018).

Yamashita, T. et al., “Affinity Improvement of a Cancer-Targeted Antibody through Alanine-Induced Adjustment of Antigen-Antibody Interface”, Structure, 5-27(3), 519-527.e5 (2019)

Sugiyama, A. et al., “Cupid and Psyche system for the diagnosis and treatment of advanced cancer.”, Proc Jpn Acad Ser B Phys Biol Sci,. 95(10), 602-611 (2020).

Fukuda, Y. et al., “High-resolution neutron crystallography visualizes an OH-bound resting state of a copper-containing nitrite reductase”, PNAS., 117 (8) 4071-4077 (2020).

Minami, T. et al., “Novel neutralizing human monoclonal antibodies against tetanus neurotoxin”, Scientific Reports, 11. 12134. (2021).