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Research overview/research content

Research overview

To elucidate the mechanism of proteins that play important roles within organisms, functional analysis based on protein structure is conducted, and protein function design and other efforts based on the information obtained in such analysis are promoted vigorously. Research has been promoted by introducing cutting-edge technologies from a variety of interdisciplinary fields. Such technologies range from the effective expression and refinement of amino acid substitution protein by using molecular biological and biochemical approaches to physicochemical methods using a 600-MHz supersensitive high-resolution NMR device, which offers the highest-performance of its kind in the School of Science, a laser Raman spectroscopic device that can sharply render the microstructures of protein, and simulation calculation based on the basic principle of physical chemistry. Research results and developed methods have an important implication as the basis for drug discovery and therapeutic development based on the molecular construction of protein, which is attracting attention in the post-genome era, the design of artificial protein as a clean functional material and other new technologies and materials that can be applied in the real world in the future.

 

 

Research content

Analysis of the structure and function of sensor protein

iron transport

Organisms must rigorously adjust and control many functions to maintain their homeostasis, and their molecular mechanisms are mediated by metallic ions and other signal transmitters. We elucidate the molecular structures of these signal transmitters, clarify the expression of their functions at a molecular level and pursue the possibility of artificially controlling them. We place special focus on the metabolic mechanism of metallic ion, and try to elucidate the molecular-theoretical image of the onset of nervous diseases, hepatitis and other diseases that are thought to be related to abnormalities of the metabolic mechanism by associating such diseases with the function of sensor protein.

 

Elucidation of the electron transfer mechanism in a respiratory chain

research_content_2respiratorychain

Oxygen-breathing organisms produce ATP effectively using electrons obtained in the glycolytic system. An efficient electron transfer process among proteins is essential for this ATP producing process, and its elucidation is not only indispensable for a molecular-theoretical explanation of energy production by oxygen-breathing organisms, but is also attracting attention in terms of realizing clean bioenergy production in the future. We are trying to elucidate and artificially control the molecular mechanism of the inter-protein electron transfer by using an ultrahigh resolution, polynuclear multidimensional NMR device.

 

Research on the structure and functions of membrane protein using nanodisks

research_content_3nanodisk

Many physiologically important proteins function when bonded with a biological membrane. Since protein is difficult to refine when bonded with a biological membrane, the structures and functions of membrane proteins under environments different from those within organisms have been discussed in past studies. Therefore, we have recently developed a method of wrapping protein in a “nanodisk,” which is a disk-shaped membrane with a radius of around 10 nm made by using lipids and proteins surrounding it to wrap protein in it. This method is used to examine the function and structure of protein under conditions closer to those within organisms, and the possibility of its application to a nano device in which protein is arranged in a certain direction.

 

Research on the formation principle of cubic protein structures

research_content_4cubicproteinstructures

It is assumed that the functions of proteins are expressed when a peptide chain maintains a certain cubic structure by weak force, such as hydrogen bonding. While such formation of cubic protein structures is thought to depend on the amino acid sequence of the peptide chain, much remains unknown about the formation principle of such structures. Therefore, we aim to elucidate the basic principle of the formation of cubic protein structures and the molecular mechanism of the functional expression and create artificially designed highly functional new proteins by following the formation process of the cubic protein structures and clarifying their molecular mechanism using a spectroscopic method developed uniquely by us.

 

Metallic ion acquiring mechanisms of pathogenic bacteria

research_content_5bacteria

Pathogenic bacteria require a variety of metallic ions to propagate, and obtain many of them from their hosts. For example, iron ion acquires heme coenzymes by drawing them from hemoglobin in blood and decomposing it. Therefore, an understanding of the metallic ion acquisition mechanism is important when considering protection from and medication against pathogenic bacteria. We are conducting research to clarify the metallic ion acquisition mechanism of pathogenic bacteria using a spectral device developed uniquely by us.

 

Development of a structure optimization method and simulation of the most stable structures of clusters and proteins using the method

A method for searching for the most stable structures of clusters and proteins with complex potential energy surfaces will be developed. This global structure optimization method will be applied to the structure calculation of clusters consisting of single molecules and atoms with a cluster size of up to several dozens or hundreds. The correlation between the obtained cluster structure and the shape of its components will be clarified. The molecular aggregation process will be examined.

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