| Project/Area Number |
24570140
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Structural biochemistry
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| Research Institution | Osaka Medical College |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
Murakawa Takeshi 大阪医科大学, 医学部, 助教 (90445990)
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| Co-Investigator(Renkei-kenkyūsha) |
Shoji Mitsuo 筑波大学, 数理物質科学研究科, 助教 (00593550)
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| Project Period (FY) |
2012-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 酵素反応機構 / ピリドキサールリン酸 / 反応速度論 / 遷移相速度論 / 反応中間体 / 反応特異性 / 基質支援触媒 / 生成物支援触媒 / ピリドキサール5'-リン酸 / プロトン化状態 / 副反応 / 補酵素 / 量子化学計算 / Ｘ線結晶解析 |
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| Outline of Final Research Achievements |
The reaction mechanism of threonine synthase (TS) was studied. The phosphate ion released from the reaction of TS with its substrate O-phosphohomoserine (OPHS) remains at the active site and forms a hydrogen bond with the hydroxy group of the reaction intermediates at the active site, thereby lowering the transition states of the pathway leading to the formation of L-threonine (normal reaction) rather than that of the release of α-aminoacrylate (main side reaction). This phosphate ion and its precursor, the phospho group of OPHS, were found to interact strongly with the principal catalytic group Lys61, and by controlling the position of the side chain of Lys61, suppress various side reactions which are expected from the versatile catalytic ability of the coenzyme pyridoxal 5'-phosphate. These results revealed the unique mechanism of TS in which the reaction specificity is brought about by substrate-assisted and product-assisted catalysis.
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