• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Concerted proton/electron transfer mechanism in cofactor-dependent enzyme

Research Project

Project/Area Number 15K05573
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Bio-related chemistry
Research InstitutionOsaka Medical College

Principal Investigator

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

Co-Investigator(Kenkyū-buntansha) 村川 武志  大阪医科大学, 医学部, 助教 (90445990)
Research Collaborator SHOJI mitsuo  
Project Period (FY) 2015-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords酵素反応機構 / プロトン移動 / 電子移動 / エネルギー準位図 / 反応駆動力 / X線結晶解析 / 反応速度論 / 補欠分子族 / 触媒反応機構 / キノタンパク質 / トーパキノン / 解離基 / pH依存性 / 遷移相速度論 / 銅イオン / ピリドキサールリン酸 / ハロゲン化物イオン
Outline of Final Research Achievements

Enzymes, which are the catalysts for the chemical processes in living cells, promote the movements of protons and electrons. However, not much effort has been paid for elucidating the origin of the driving forces for these movements. In this study, a methodology was developed in order to clarify the driving force for the most probable reaction pathway. In this methodology, the reaction intermediates with all possible protonation and redox states are first classified according to the numbers of protons and electrons, and then the energy level is plotted against the coordinates of the reaction step, protonation state, and the redox state. The obtained energy landscape can be used to draw the reaction pathway, and combined with high-resolution structural methods, elucidate the structural elements of the driving force for the proton and electron movements.

Academic Significance and Societal Importance of the Research Achievements

今までの酵素反応機構の研究は現象の追跡に終始していたが,本研究はその現象がどのような力によってもたらされているかという,本質的な要因を明確にする方法論を確立したところに学術的な意義がある.また,この方法論によって酵素反応機構を明らかにする研究の方向性が明確になることは,現在,洗剤などの日常生活から薬品や各種素材の製造といった工業分野に至るまで酵素の触媒能力が応用されている領域において,望みの機能を持った酵素の開発を容易にすることにつながるという社会的意義がある.

Report

(5 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (9 results)

All 2018 2017 2016 2015

All Journal Article (4 results) (of which Peer Reviewed: 4 results) Presentation (5 results) (of which Int'l Joint Research: 3 results,  Invited: 3 results)

  • [Journal Article] In crystallo thermodynamic analysis of conformational change of the topaquinone cofactor in bacterial copper amine oxidase2018

    • Author(s)
      Murakawa Takeshi、Baba Seiki、Kawano Yoshiaki、Hayashi Hideyuki、Yano Takato、Kumasaka Takashi、Yamamoto Masaki、Tanizawa Katsuyuki、Okajima Toshihide
    • Journal Title

      Proceedings of the National Academy of Sciences

      Volume: 116 Issue: 1 Pages: 135-140

    • DOI

      10.1073/pnas.1811837116

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Molecular Mechanism of the Reaction Specificity in Threonine Synthase: Importance of the Substrate Conformations2017

    • Author(s)
      Ujiie Yuzuru,Tanaka Wataru,Hanaoka Kyohei,Harada Ryuhei,Kayanuma Megumi,Shoji Mitsuo,Murakawa Takeshi,Ishida Toyokazu,Shigeta Yasuteru,Hayashi Hideyuki
    • Journal Title

      The Journal of Physical Chemistry B

      Volume: 121 Issue: 22 Pages: 5536-5543

    • DOI

      10.1021/acs.jpcb.7b02932

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Role of the Tyr270 residue in 2-methyl-3-hydroxypyridine-5-carboxylic acid oxygenase from Mesorhizobium loti.2017

    • Author(s)
      Kobayashi J., Yoshida H., Yagi T., Kamitori S., Hayashi H., Mizutani K., Takahashi N., Mikami B.
    • Journal Title

      J. Biosci. Bioeng.

      Volume: 123 Issue: 2 Pages: 154-162

    • DOI

      10.1016/j.jbiosc.2016.07.022

    • NAID

      40021112404

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Probing the Catalytic Mechanism of Copper Amine Oxidase from Arthrobacter globiformis with Halide Ions.2015

    • Author(s)
      Murakawa, T., Hamaguchi, A., Nakanishi, S., Kataoka, M., Nakai, T., Kawano, Y., Yamaguchi, H., Hayashi, H., Tanizawa, K., and Okajima, T.
    • Journal Title

      J. Biol. Chem.

      Volume: 290 Issue: 38 Pages: 23094-23109

    • DOI

      10.1074/jbc.m115.662726

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Presentation] ヒスチジノールリン酸アミノトランスフェラーゼの基質認識機構2018

    • Author(s)
      林秀行,村川武志
    • Organizer
      日本化学会第98春季年会
    • Related Report
      2017 Research-status Report
  • [Presentation] トレオニン合成酵素の反応機構2018

    • Author(s)
      町田康博,村川武志,境晶子,林秀行
    • Organizer
      日本ビタミン学会第70回大会
    • Related Report
      2017 Research-status Report
  • [Presentation] Strain as the driving force for catalysis in aspartate aminotransferase2016

    • Author(s)
      Hideyuki Hayashi and Takeshi Murakawa
    • Organizer
      V Russian Congress on Biochemistry
    • Place of Presentation
      Sochi, Russian Federation
    • Year and Date
      2016-10-04
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Energetics of the proton-transfer mechanism in aspartate aminotransferase2015

    • Author(s)
      Hideyuki Hayashi, Takeshi Murakawa, Mitsuo Shoji, Yasuteru Shigeta
    • Organizer
      Pacifichem 2015
    • Place of Presentation
      Honolulu, USA
    • Year and Date
      2015-12-15
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] "Super-closed” structure of aspartate aminotransferase unveils the mechanism for the substate-induced transaldimination process2015

    • Author(s)
      Hideyuki Hayashi, Takeshi Murakawa, Ikuko Miyahara
    • Organizer
      Biocatalysis-2015
    • Place of Presentation
      Moscow, Russia
    • Year and Date
      2015-06-21
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research / Invited

URL: 

Published: 2015-04-16   Modified: 2020-03-30  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi