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Investigation of isomerization mechanism of aspartic acid involved in the development of cataract

Research Project

Project/Area Number 16K16605
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Applied health science
Research InstitutionTokyo University of Pharmacy and Life Science (2017-2019)
International University of Health and Welfare (2016)

Principal Investigator

Sakaue Hiroaki  東京薬科大学, 薬学部, 助教 (80734855)

Project Period (FY) 2016-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
KeywordsD-アミノ酸 / アスパラギン酸 / 異性化 / 紫外線 / アスパラギン酸残基の異性化 / タンパク質
Outline of Final Research Achievements

In this study, we succeeded in developing a rapid method for detecting isomerization of aspartic acid (Asp) residue and glutamic acid (Glu) residue. Aromatic amino acids such as tryptophan and tyrosine suppressed the isomerization reaction of Asp residues in peptides by ultraviolet. It was considered that the energy absorbed by the aromatic amino acids were not transferred to the isomerization reaction of Asp and was used for decomposition to protect the peptide from isomerization. On the other hand, it was also suggested that pH change and coexistence of reducing sugars promote isomerization. It was suggested that UV irradiation accelerated the isomerization of Asp indirectly.

Academic Significance and Societal Importance of the Research Achievements

タンパク質中のアスパラギン酸残基の異性化は、タンパク質機能を劇的に変化させることを以前の研究により明らかにしている。白内障の発症と水晶体クリスタリン中のアスパラギン酸残基の異性化には相関があることから、アスパラギン酸残基の異性化を抑制することは白内障の予防薬や発症時期を遅らせる薬剤の開発に繋がる。本研究により、芳香族アミノ酸はアスパラギン酸残基の異性化を抑制することが明らかになった。また、還元性を有する糖やわずかなpHの変化が異性化を促進することが示唆された。本研究で得られた知見は、アスパラギン酸残基の新たな異性化促進メカニズムを考察する上で有意義なものであると言える。

Report

(5 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (4 results)

All 2020 2018 2017

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 1 results) Presentation (1 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results)

  • [Journal Article] D-Alanine Is Reduced by Ocular Hypertension in the Rat Retina.2020

    • Author(s)
      Takashi Kanamoto, Hiroaki Sakaue, Yasushi Kitaoka, Ryo Asaoka, Kei Tobiume, and Yoshiaki Kiuchi
    • Journal Title

      Current Eye Research

      Volume: 45 Issue: 4 Pages: 490-495

    • DOI

      10.1080/02713683.2019.1666995

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] D-Amino acids in protein: The mirror of life as a molecular index of aging2018

    • Author(s)
      Fujii Noriko、Takata Takumi、Fujii Norihiko、Aki Kenzo、Sakaue Hiroaki
    • Journal Title

      Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics

      Volume: in press Issue: 7 Pages: 840-847

    • DOI

      10.1016/j.bbapap.2018.03.001

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Isomeric Replacement of a Single Aspartic Acid Induces a Marked Change in Protein Function: The Example of Ribonuclease A2017

    • Author(s)
      Sakaue H, Kinouchi T, Fujii N, Takumi T, Fujii N.
    • Journal Title

      ACS Omega

      Volume: 2 Issue: 1 Pages: 260-267

    • DOI

      10.1021/acsomega.6b00346

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] A single aspartyl isomer at a specific site induces a change in protein function.2017

    • Author(s)
      Hiroaki Sakaue
    • Organizer
      The 3rd International Conference of D-Amino Acid Research
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research / Invited

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Published: 2016-04-21   Modified: 2021-02-19  

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