Supramolecular Science Laboratory
|Staff & Contact|
|Educational Staff||Prof. Shun Hirota
Associate Prof. Takashi Matsuo
Assistant Prof. Satoshi Nagao, Masaru Yamanaka, Tai Hulin
|Contact ||TEL: +81-743-72-6110|
Education and Research Activities in the Laboratory
In living organisms, a variety of biomolecules such as proteins, DNA, and sugars form unique supramolecular assemblies to maintain bio-functions. Based on chemical knowledge of the functions and structures of these bio-supramolecules at the molecular level, our laboratory focuses on elucidation of the function mechanisms and design/applications of bio-supramolecules using various spectroscopic analysis methods, protein engineering techniques, and organic syntheses.
1. New bio-supramolecules creation
We develop 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).
2. Functional protein creation by protein design Creation of photo-reactive proteins, peptides, and metal complexes
We design photo-control systems using artificial proteins and metal complexeswith multi-active sites exhibiting(e.g. antibacterial activity and ligand binding propertya two metal complexes with azobenzene for a reversible on-off controlled DNA cleavage, (Fig. 2). These systems proteins are attracting attention in the biotechnology and pharmaceutical science fields, due to their potential application for gene manipulation and cancer treatments.
3. Elucidation and inhibition of protein denaturalization processes
Accumulation of proteins with unusual structures in tissues causes various diseases such as Alzheimer’s disease, Parkinson’s disease, and mad cow disease (Conformation diseases). We investigate denaturalization of these proteins at the molecular level and develop strategies to inhibit this denaturalization.
4. Elucidation of rReaction mechanism elucidation of metalloenzymes
To utilize the energy production system in nature, we elucidate the H2 production and decomposition mechanism of a metalloenzyme, hydrogenase, using spectroscopic methods. and
5. functional Functional analysis of physiologically active molecules for medicinal chemistry
To understand and regulate the extraordinary efficiency of bioreactions, we study the functional expressionaction mechanisms of physiologically active small molecules from the perspective of medicinal chemistry.
65. Functional protein creation through synthetic chemistry approaches
We precisely designed organometallic complexes-containing proteinchemically attractive biocatalysts and artificial proteins with ON/OFF switchable functions, thereby creating “molecular design-based functional biomolecules” with unique functions. This strategy uses the advantage of the complementarity of synthetic chemistry and biochemical approaches, in combination with genetic engineering methods (Fig. 3).
Explanatory Pictures of Research Activities
Elucidated structures of cytochrome c supramolecules.
- Fig. 2
Creation of antibacterial protein supramoleculesPhoto-controlled DNA cleavage by metal complex-conjugated azobenzene.
- Fig. 3
Olefin metathesis in protein matrixX-ray crystallographic structure of an artificial fluorescent protein constructed by a combination of genetic and synthetic methods.
Recent Research Papers and Achievements
1. Y.-W. Lin, S. Nagao, M. Zhang, Y. Shomura, Y. Higuchi, S. Hirota, “Rational design of heterodimeric protein using domain swapping for myoglobin”, Angew. Chem. Int. Ed. 54 511-515 (2015).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).
2. T. Matsuo, C. Imai, T. Yoshida, T. Saito, T. Hayashi, S. HirotaA.Fujii, Y. Sekiguchi, H. Matsumura, T. Inoue, W.-S. Chung. S. Hirota, T. Matsuo, “Excimer Eemission Pproperties on Ppyrene-labeled Pprotein Ssurface: Ccorrelation between Eemission Sspectra, Rring Sstacking Mmodes and Fflexibilities of Ppyrene PprobesCreation of an artificial metalloprotein with a Hoveyda-Grubbs catalyst moiety through the intrinsic inhibition mechanism of -chymotrypsin”, Bioconjugate Chem. Chem. Commun. 2648 5371662-5481664 (20152).