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Structural analysis of serine peptidase for construction of screening tool for novel biologically active substances

Research Project

Project/Area Number 26450124
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Applied biochemistry
Research InstitutionTottori University

Principal Investigator

Arima Jiro  鳥取大学, 農学部, 准教授 (80393411)

Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywordsアミノリシス / D体特異的アミノ酸アミド加水分解酵素 / 結晶構造解析 / 基質結合部位 / アシル受容体 / ペプチド結合形成反応 / 副反応 / 立体構造 / family S12ペプチダーゼ / 立体構造解析 / ペプチド結合形成
Outline of Final Research Achievements

Serine peptidases that exhibit the catalytic ability of “aminolysis” are capable of utilizing biocatalyst for peptide synthesis. Therefore, such enzymes are considered to be useful as screening tool for novel biologically active substances. To clarify the mechanism of aminolysis function of D-stereospecific amino acid amide hydrolase (DAH) that exhibits high aminolysis function, the crystal structure of the enzyme was determined at a resolution of 1.6 angstrom. DAH possesses a large cavity that leads to the catalytic center, and there is a small pocked close to the catalytic center. By substitution of the residues that constitute the catalytic pocket, we found that the structural modification of Ile338 enhanced the aminolytic ability and were broaden the acyl acceptor specificity. The modification of pocket shape by the mutation is considered to be related to the increase in aminolysis activity of DAH

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (13 results)

All 2017 2016 2015 2014

All Journal Article (2 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 2 results) Presentation (11 results) (of which Int'l Joint Research: 4 results,  Invited: 2 results)

  • [Journal Article] Effect of oxidation of the non-catalytic b-propeller domain on the substrate specificity of prolyl oligopeptidase from Pleurotus eryngii2017

    • Author(s)
      Shota Tokai, Tomohiro Bito, Katsuhiko Shimizu, Jiro Arima
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 487 Issue: 2 Pages: 356-361

    • DOI

      10.1016/j.bbrc.2017.04.064

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Crystal structure of D-stereospecific amidohydrolase from Streptomyces sp. 82F2: insight into the structural factors for substrate specificity.2016

    • Author(s)
      Arima J, Shimone K, Miyatani K, Tsunehara Y, Isoda Y, Hino T, Nagano S
    • Journal Title

      FEBS Journal

      Volume: 283 Issue: 2 Pages: 337-349

    • DOI

      10.1111/febs.13579

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] D-stereospecific amidohydrolase from Streptomyces sp. 82F2 that exhibits peptide-bond formation activity.2016

    • Author(s)
      Yasmeen Elyas, Kazusa Miyatani, Tomohiro Bito, Jiro Arima
    • Organizer
      The International Joint Symposium between Japan and Korea (AFELiSA) 2016
    • Place of Presentation
      Daejeon, Korea
    • Year and Date
      2016-11-09
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Eryngase, a serine aminopeptidase of Pleurotus eryngii, the substrate specificity of which is changed by oxidation2016

    • Author(s)
      Shota Tokai, Tomohiro Bito, Jiro Arima
    • Organizer
      The International Joint Symposium between Japan and Korea (AFELiSA) 2016
    • Place of Presentation
      Daejeon, Korea
    • Year and Date
      2016-11-09
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] エリンギ由来セリンアミノペプチダーゼ:非触媒ドメイン残基の酸化による基質特異性の変化2016

    • Author(s)
      東海彰太、有馬二朗
    • Organizer
      2016年度日本生物工学会全国大会
    • Place of Presentation
      富山国際会議場(富山)
    • Year and Date
      2016-09-28
    • Related Report
      2016 Annual Research Report
  • [Presentation] D-アミノ酸アミド加水分解酵素の活性部位ポケットを形成する残基と副反応“ペプチド結合形成能”との相関2016

    • Author(s)
      宮谷一紗、有馬二朗
    • Organizer
      2016年度日本農芸化学会全国大会
    • Place of Presentation
      札幌コンベンションセンター(札幌市)
    • Year and Date
      2016-03-27
    • Related Report
      2015 Research-status Report
  • [Presentation] Construction of non-natural dipeptide library by peptide bond formation reaction catalyzed by D-stereospecific amidohydrolase.2015

    • Author(s)
      Yuka Tsunehara, Akira Tamura, Yoshitaka Isoda, Jiro Arima
    • Organizer
      The International Chemical Congress of PACIFIC BASIN SOCIETIES (PACIFICHEM) 2015
    • Place of Presentation
      Hawaii Convention Center (Honolulu, Hawaii, USA)
    • Year and Date
      2015-12-16
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Cavity size of D-stereospecific amidohydrolase relates to its side reaction “aminolysis”2015

    • Author(s)
      Kazusa Miyatani, Ayaka Ota, Jiro Arima
    • Organizer
      The International Chemical Congress of PACIFIC BASIN SOCIETIES (PACIFICHEM) 2015
    • Place of Presentation
      Hawaii Convention Center (Honolulu, Hawaii, USA)
    • Year and Date
      2015-12-16
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] ペプチド分解酵素のアミノリシスによるペプチド結合の形成とその応用2015

    • Author(s)
      有馬二朗
    • Organizer
      2015年度日本農芸化学会中四国支部例会
    • Place of Presentation
      鳥取大学(鳥取市)
    • Year and Date
      2015-06-13
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] D-アミノ酸アミド加水分解酵素の構造と誤作動 「ペプチド結合形成能」との相関2015

    • Author(s)
      宮谷一紗、森信寛、有馬二朗
    • Organizer
      2015年度日本農芸化学会全国大会
    • Place of Presentation
      岡山大学農学部(岡山市)
    • Year and Date
      2015-03-26
    • Related Report
      2014 Research-status Report
  • [Presentation] 酵素反応生成物の利用可能性を探る ~ペプチド分解酵素の誤作動によるアミノ酸同士の結合とその応用~2014

    • Author(s)
      有馬二朗
    • Organizer
      日本農芸化学会中四国支部若手シンポジウム
    • Place of Presentation
      愛媛大学農学部(松山市)
    • Year and Date
      2014-09-20
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] 構造からみたD体特異的アミド加水分解酵素の誤作動反応2014

    • Author(s)
      有馬二朗、太田朱香、宮谷一紗、森信寛
    • Organizer
      2014年度日本生物工学会全国大会
    • Place of Presentation
      札幌コンベンションセンター(札幌市)
    • Year and Date
      2014-09-09 – 2014-09-11
    • Related Report
      2014 Research-status Report
  • [Presentation] ペプチド結合形成反応を触媒する放線菌由来D体特異的アミド加水分解酵素2014

    • Author(s)
      有馬二朗、太田朱香、森信寛、日野智也、永野真吾
    • Organizer
      第6回日本生物物理学会中四国支部大会
    • Place of Presentation
      とりぎん文化会館(鳥取市)
    • Year and Date
      2014-05-17 – 2014-05-18
    • Related Report
      2014 Research-status Report

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Published: 2014-04-04   Modified: 2018-03-22  

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