Prof. Shun Hirota
|Biofunctional chemistry, supramolecular science, biomolecular science, protein, spectroscopy，organic chemistry, bioinorganic chemistry, coordination chemistry|
Education and Research Activities in the Laboratory
In living organisms, a variety of biomolecules such as protein, DNA, and sugar form unique supramolecular assemblies to maintain life activities. Based on the chemical knowledge of the functions and structures of these bio-supramolecules at molecular level, Supramolecular Science Laboratory focuses on elucidation of the function mechanisms and design/applications of bio-supramolecules using various spectroscopic analysis methods, protein engineering technique, and organic synthesis. Particularly, we are working on the following subjects:
(1) Creation of novel supramolecules with reference to excellent characteristics demonstrated in living organisms
(2) Creation of artificial proteins with unique non-natural functions
(3) Development and application of new photoreactive biomolecules
(4) Elucidation of the mechanism of protein denaturalization, which is considered to cause conformation diseases, such as Alzheimer’s disease, Parkinson’s disease, and mad cow disease, and development of methods to inhibit protein denaturalization.
Creation of new bio-supramolecules
We are creating new protein supramolecules and polymers for functional biomaterials based on a new concept, in which a protein molecule is used as a structural unit (Fig.1).
Creation of photoreactive proteins, peptides, and metal complexes
We have succeeded in optical controlling formation of a protein structure and observing its protein folding process. We also linked two metal complexes with photoisomerizable azobenzene and used the azobenzene-linked complex to reversibly on-off control its DNA cleavage activity with light (Fig. 2). These results are attracting attention in the biotechnology and pharmaceutical science fields, due to its potential application to gene manipulation and cancer treatments.
Elucidation and inhibition of protein denaturalization processes
Accumulation of peptides/proteins (amyloid β peptide, prion protein, etc.) with unusual structures in tissues causes various diseases such as Alzheimer’s disease, Parkinson’s disease, and mad cow disease. These diseases are comprehensively called “conformation diseases”. However, the denaturalization mechanism of these proteins is unsolved. In our laboratory, we are working on understanding protein denaturalization of these proteins at the molecular level and developing strategies to inhibit the denaturalization.
Elucidation of the reaction mechanism of in vivo enzymes and functional analysis of physiologically active molecules for medicinal chemistry
Biomolecules function more efficiently in vivo than when they are controlled in laboratories. We aim to understand the refined reactions of these biomolecules at molecular level for application of these reactions (Fig.3). We are also studying the functional expression mechanism of physiologically active small molecules from the perspective of medicinal chemistry.
Creation of functional proteins by taking advantage of the synthetic chemistry approach
We are introducing precisely designed organometallic complexes into natural proteins by organic or complex synthesis, as well as forming metal complexes through amino-acid side chains, thereby creating “molecular design-based functional biomolecules” with unique functions. We are also developing techniques for designing unique biomolecules, taking the advantage of the complementarity of synthetic chemistry and biochemical approaches, in combination with genetic engineering methods.
Explanatory Pictures of Research Activities
Recent Research Papers and Achievements
“Cytochrome c polymerization by successive domain swapping at the C-terminal helix,” S. Hirota, Y. Hattori, S. Nagao, M. Taketa, H. Komori, H. Kamikubo, Z. Wang, I. Takahashi, S. Negi, Y. Sugiura, M. Kataoka, Y. Higuchi, Proc. Natl. Acad. Sci. USA, 107, 12854-12859 (2010).
“Structural Basis of the Lactate-Dependent Allosteric Regulation of Oxygen Binding in Arthropod Hemocyanin,” S. Hirota, N. Tanaka, I. Micetic, P. Di Muro, S. Nagao, H. Kitagishi, K. Kano, R. S. Magliozzo, J. Peisach, M. Beltramini, L. Bubacco, J. Biol. Chem., 285, 19338-19345 (2010).
“Regulating Copper-Binding Affinity with Photoisomerizable Azobenzene Ligand by Construction of a Self-Assembled Monolayer,” I. Takahashi, Y. Honda, S. Hirota, Angew. Chem. Int. Ed., 48, 6065-6068 (2009).
“Meso-Unsubstituted Iron Corrole in Hemoproteins: Remarkable Differences in Effects on Peroxidase Activities between Myoglobin and Horseradish Peroxidase,” T. Matsuo, A. Hayashi, M. Abe, T. Matsuda, Y. Hisaeda, T. Hayashi, J. Am. Chem. Soc., 131, 15124-15125 (2009).
“Molecular Basis of the Bohr Effect in Arthropod Hemocyanin,” S. Hirota, T. Kawahara, M. Beltramini, P. Di Muro, R. S. Magliozzo, J. Peisach, L. S. Powers, N Tanaka, S Nagao, L. Bubacco, J. Biol. Chem., 283, 31941-31948 (2008).
“Photocontrol of Spatial Orientation and DNA Cleavage Activity of Copper(II)-Bound Dipeptides Linked by an Azobenzene Derivative,” H. Prakash, A. Shodai, H. Yasui, H. Sakurai, S. Hirota, Inorg. Chem., 47, 5045-5047 (2008).
“Conformational Changes during Apoplastocyanin Folding Observed by Photocleavable Modification and Transient Grating,” S. Hirota, Y. Fujimoto, J. Choi, N. Baden, N. Katagiri, M. Akiyama, R. Hulsker, M. Ubbink, T. Okajima, T. Takabe, N. Funasaki, Y. Watanabe, M. Terazima, J. Am. Chem. Soc., 128, 7551-7558 (2006).