| Co-Investigator(Kenkyū-buntansha) |
MORIMOTO Yukio Kyoto University, Research Reactor Institute, Professor, 原子炉実験所, 教授 (80200450)
MIYAHARA Ikuko Osaka City University, Graduate School of Science, Lecturer, 大学院・理学研究科, 講師 (40271176)
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| Research Abstract |
High-resolution Structures of natural composite catalysts such as glutamine amidotransferase, and allosteric CTP synthetase, PLP-dependent enzymes, and FAD-dependent enzymes have been determined by X-ray crystallographic methods. The substrate recognition, induced fit, and reaction mechanism have been analyzed to understand the molecular design which enables these enzymes to act as biocatalysts.
1. Three-dimensional structures of natural biocatalysts and active-site designs. (1)Imidazole glycerol phosphate synthetase. The ammonia transfer mechanism through a molecular channel linking glutaminase and synthase sites has been proposed. (2)CTP (cytidine 5'-triphosphate) synthetase. The mechanism for ammonia tunneling, allosteric GTP activation, and enzyme activation induced by ATP and UTP-dependent conformational change has been examined. (3)Argininosuccinate synthetase. The substrate recognition mechanism and pseudo time-resolved X-ray analysis has been performed in order to clarify the st
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ereochemistry of the reaction. (4) Quinohemoprotein aminedehydrogenase. A novel quinine cofactor and highly unusual thioether cross-bridges have been identified.
2. Three-dimensional structures of PLP-dependent enzymes. (1)Histidinol-phosphate aminotransferase. The active-site design for double substrate recognition has been analyzed. (2)Branched-chain amino acid aminotransferase. The double substrate recognition and reaction mechanism have been elucidated. (3)Threonine synthase. The reaction catalyzed is expected to proceed through all the intermediates utilized by PLP-dependent enzymes. Stereochemistry of the reaction has been proposed. (4)Glutamine/kunerenine aminotransferase. In mammals, the enzyme is involved in CNS events. The substrate recognition and induced fit phenomena have been examined.
3. Three dimensional structures of FAD-dependent enzymes. (1)Medium-chain acyl-CoA oxidase. On the basis of structural comparison with the homologue (acyl-coA dehydrogenase), the molecular design of the oxidase has been analyzed. (2)Medium-chain acyl-CoA dehydrogenase as the transition state analogue. The transition state of the reaction has been examined based on the X-ray structure and MO calculation of the complex. Less
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