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Reaction specificity of pyridoxal enzymes

Research Project

Project/Area Number 24570140
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Structural biochemistry
Research InstitutionOsaka Medical College

Principal Investigator

Hayashi Hideyuki  大阪医科大学, 医学部, 教授 (00183913)

Co-Investigator(Kenkyū-buntansha) Murakawa Takeshi  大阪医科大学, 医学部, 助教 (90445990)
Co-Investigator(Renkei-kenkyūsha) Shoji Mitsuo  筑波大学, 数理物質科学研究科, 助教 (00593550)
Project Period (FY) 2012-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
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)
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
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.

Report

(5 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (13 results)

All 2015 2014 2013 2012 Other

All Journal Article (1 results) (of which Peer Reviewed: 1 results) Presentation (11 results) (of which Int'l Joint Research: 2 results) Remarks (1 results)

  • [Journal Article] A QM/MM Study of the l-Threonine Formation Reaction of Threonine Synthase: Implications into the Mechanism of the Reaction Specificity.2014

    • Author(s)
      Shoji, M., Hanaoka, K., Ujiie, Y., Tanaka, W., Kondo, D., Umeda, H., Kamoshida, Y., Kayanuma, M., Kamiya, K., Shiraishi, K., Machida, Y., Murakawa, T., and Hayashi, H.
    • Journal Title

      J. Am. Chem. Soc.

      Volume: 136 Issue: 12 Pages: 4525-4533

    • DOI

      10.1021/ja408780c

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] Molecular dynamics study on the molecular mechanism of product-assisted catalysis in threonine synthase2015

    • Author(s)
      氏家謙,田中弥,庄司光男,原田隆平,栢沼愛,重田育照,村川武志,林秀行
    • Organizer
      第43回構造活性相関シンポジウム・第10回薬物の分子設計と開発に関する日中シンポジウム
    • Place of Presentation
      新潟
    • Year and Date
      2015-09-27
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] トレオニン合成酵素における生成物支援触媒機構についての理論的解明2015

    • Author(s)
      庄司光男,氏家謙,栢沼愛,重田育照,村川武志,林秀行
    • Organizer
      第53回日本生物物理学会年会
    • Place of Presentation
      金沢
    • Year and Date
      2015-09-13
    • Related Report
      2015 Annual Research Report
  • [Presentation] Molecular dynamics study on the key catalytic intermediates of threonine synthase2015

    • Author(s)
      Mitsuo Shoji, Yuzuru Ujiie, Ryuhei Harada, Megumi Kayanuma, Yasuteru Shigeta, Takeshi Murakawa, Hideyuki Hayashi
    • Organizer
      The 29th Annual Symposium of the Protein Society
    • Place of Presentation
      Barcelona, Spain
    • Year and Date
      2015-07-22
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] トレオニン合成酵素の触媒過程前半部分の解析2015

    • Author(s)
      林秀行,村川武志,庄司光男
    • Organizer
      日本化学会第95春季年会
    • Place of Presentation
      船橋
    • Year and Date
      2015-03-26 – 2015-03-29
    • Related Report
      2014 Research-status Report
  • [Presentation] トレオニン合成酵素の触媒反応 前半部分の反応機構解析2014

    • Author(s)
      町田康博,村川武志,庄司光男,林秀行
    • Organizer
      第61回日本生化学会近畿支部例会
    • Place of Presentation
      京都
    • Year and Date
      2014-05-17 – 2015-05-17
    • Related Report
      2014 Research-status Report
  • [Presentation] トレオニン合成酵素の反応機構についての理論的研究:反応特異性決定過程の解明2014

    • Author(s)
      庄司光男,氏家謙,田中弥,栢沼愛,梅田宏明,町田康博,村川武志,林秀行
    • Organizer
      日本化学会第94春季年会
    • Place of Presentation
      名古屋
    • Related Report
      2013 Research-status Report
  • [Presentation] トレオニン合成酵素における反応特異性決定過程の理論解明2013

    • Author(s)
      庄司光男,花岡恭平,氏家謙,田中弥,梅田宏明,栢沼愛,神谷克政,白石賢二,町田康博,村川武志,林秀行
    • Organizer
      第13回日本蛋白質科学会年会
    • Place of Presentation
      鳥取
    • Related Report
      2013 Research-status Report
  • [Presentation] 分子動力学法によるトレオニン合成酵素の反応特異性についての理論的解明2013

    • Author(s)
      氏家謙,田中弥,花岡恭平,庄司光男,栢沼愛,神谷克政,白石賢二,町田康博,村川武志,林秀行
    • Organizer
      第86回日本生化学会大会
    • Place of Presentation
      横浜
    • Related Report
      2013 Research-status Report
  • [Presentation] トレオニン合成酵素における反応特異性についての理論的解明2013

    • Author(s)
      庄司光男,氏家謙,田中弥,花岡恭平,梅田宏明,栢沼愛,神谷克政,白石賢二,町田康博,村川武志,林秀行
    • Organizer
      第86回日本生化学会大会
    • Place of Presentation
      横浜
    • Related Report
      2013 Research-status Report
  • [Presentation] トレオニン合成酵素の触媒性リン酸イオン結合残基の役割2012

    • Author(s)
      町田 康博,村川 武志,庄司 光男,林 秀行
    • Organizer
      第85回日本生化学会大会
    • Place of Presentation
      マリンメッセ福岡
    • Related Report
      2012 Research-status Report
  • [Presentation] トレオニン合成酵素におけるリン酸脱離以降の反応機構についての理論的解明2012

    • Author(s)
      庄司 光男,花岡 恭平,近藤 大生,田口 真彦,栢沼 愛,梅田 宏明,鴨志田 良和,神谷 克政,白石 賢二,村川 武志,林 秀行
    • Organizer
      第85回日本生化学会大会
    • Place of Presentation
      マリンメッセ福岡
    • Related Report
      2012 Research-status Report
  • [Remarks] 必須アミノ酸「トレオニン」生合成の最終過程が明らかに-スーパーコンピュータで網羅的に反応経路を探索

    • URL

      http://www.tsukuba.ac.jp/attention-research/p201403141400.html

    • Related Report
      2013 Research-status Report

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Published: 2013-05-31   Modified: 2019-07-29  

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