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Elucidation of the structure-function relationship for the unique exopeptidase family in ClanPA that is the largest peptidase Clan.

Research Project

Project/Area Number 17H03790
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Applied microbiology
Research InstitutionNagaoka University of Technology

Principal Investigator

Ogasawara Wataru  長岡技術科学大学, 工学研究科, 教授 (40292172)

Project Period (FY) 2017-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥15,990,000 (Direct Cost: ¥12,300,000、Indirect Cost: ¥3,690,000)
Fiscal Year 2020: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Fiscal Year 2019: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2018: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2017: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000)
Keywordsペプチダーゼ / インヒビター / カイネティクス / 立体構造 / S46ペプチダーゼ / 基質認識機構 / ジペプチジルペプチダーゼ / 構造機能相関 / 基質認識機構認識機構
Outline of Final Research Achievements

In this study, we analyzed the structure-function relationship of dipeptidyl peptidase (DPP) Family-S46 peptidase, which is involved in bacterial growth, and screened for inhibitory compounds. S46 peptidase shoewd specificity for hydrophobic amino acid residues at the N-terminus of the substrate and for asparagine residues. Furthermore, in silico screening of S46 peptidase by structural analysis revealed the first inhibitors of S46 peptidase in the world. The inhibitors had no effect for the growth of Escherichia coli, but inhibited the growth of periodontal bacteria.

Academic Significance and Societal Importance of the Research Achievements

解析対象のS46ペプチダーゼは歯周病原因菌や多剤耐性日和見感染菌の生育に重要な酵素である。加えてヒトはS46ペプチダーゼの類縁酵素を保持しないことから、本酵素は糖非発酵性病原性細菌に対する新規抗菌薬の有望な標的因子である。つまり本研究においてS46ペプチダーゼの構造機能相関を解析し阻害化合物の見いだすことは、微生物におけるタンパク質の資化機構解明に寄与するだけでなく、歯周病原因菌や多剤耐性日和見感染菌を抑制可能な創薬開発につながる極めて意義のある研究である。

Report

(5 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Research Products

    (31 results)

All 2021 2020 2019 2018 2017 Other

All Journal Article (5 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 5 results,  Open Access: 5 results) Presentation (13 results) (of which Int'l Joint Research: 3 results) Remarks (9 results) Patent(Industrial Property Rights) (4 results) (of which Overseas: 1 results)

  • [Journal Article] Structural basis for an exceptionally strong preference for asparagine residue at the S2 subsite of Stenotrophomonas maltophilia dipeptidyl peptidase 72021

    • Author(s)
      22)Akihiro Nakamura, Yoshiyuki Suzuki, Yasumitsu Sakamoto, Saori Roppongi, Chisato Kushibiki, Natsuri Yonezawa, Masato Takahashi, Yosuke Shida, Hiroaki Gouda, Takamasa Nonaka, Nobutada Tanaka, Wataru Ogasawara
    • Journal Title

      scinentific reports

      Volume: 11 Issue: 1 Pages: 7929-7929

    • DOI

      10.1038/s41598-021-86965-x

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The Crystal Structure of Peptidase Toward Drug Discovery2019

    • Author(s)
      阪本泰光、六本木沙織、鈴木義之、石原司、日高興士、中村彰宏、本間宣行、小笠原渉、田中信忠
    • Journal Title

      International journal of microgravity science and application

      Volume: 36 Issue: 1 Pages: 360106

    • DOI

      10.15011//jasma.36.360106

    • NAID

      130007842629

    • ISSN
      2188-9783
    • Year and Date
      2019-01-31
    • Related Report
      2019 Annual Research Report 2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Fragment-based discovery of the first nonpeptidyl inhibitor of an S46 family peptidase2019

    • Author(s)
      YasumitsuSakamoto,YoshiyukiSuzuki,AkihiroNakamura,YurieWatanabe,MizukiSekiya,SaoriRoppongi,ChisatoKushibiki,IppeiIizuka,OsamuTani,HitoshiSakashita,KojiInaka,HiroakiTanaka,MitsuguYamada,KazunoriOhta,NobuyukiHonma,YosukeShida,WataruOgasawara,MayumiNakanishi-Matsui,TakamasaNonaka,HiroakiGouda & NobutadaTanaka
    • Journal Title

      Scientific Reports

      Volume: 9 Issue: 1 Pages: 13587-13587

    • DOI

      10.1038/s41598-019-49984-3

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Crystal structures of a bacterial dipeptidyl peptidase IV reveal a novel substrate recognition mechanism distinct from that of mammalian orthologues2018

    • Author(s)
      Roppongi Saori、Suzuki Yoshiyuki、Tateoka Chika、Fujimoto Mayu、Morisawa Saori、Iizuka Ippei、Nakamura Akihiro、Honma Nobuyuki、Shida Yosuke、Ogasawara Wataru、Tanaka Nobutada、Sakamoto Yasumitsu、Nonaka Takamasa
    • Journal Title

      Scientific Reports

      Volume: 8 Issue: 1 Pages: 2714-2714

    • DOI

      10.1038/s41598-018-21056-y

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Periplasmic form of dipeptidyl aminopeptidase IV from Pseudoxanthomonas mexicana WO24: purification, kinetic characterization, crystallization and X‐ray crystallographic analysis2017

    • Author(s)
      Saori Roppongi Chika Tateoka Mayu Fujimoto Ippei Iizuka Saori Morisawa Akihiro Nakamura Nobuyuki Honma Yoshiyuki Suzuki Yosuke Shida Wataru Ogasawara Nobutada Tanaka Yasumitsu Sakamoto Takamasa Nonaka
    • Journal Title

      Acta Crystallographica Section F

      Volume: 73 Issue: 11 Pages: 501-606

    • DOI

      10.1107/s2053230x17014911

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 抗菌薬開発に資するPorphyromonas gingivalis 由来Dipeptidylpeptidase11の構造解析と阻害化合物探索2020

    • Author(s)
      中村 彰宏, 阪本 泰光, 鈴木 義之, 渡邉 友里江, 關谷 瑞樹, 六本木 沙織, 櫛引 千里, 飯塚 一平,谷 修, 阪下 日登志, 伊中 浩治, 田仲 広明, 山田 貢, 大田 和敬, 本間 宣行, 志田 洋介, 中西 真弓, 野中 孝昌, 合田 浩明, 田中 信忠, 小笠原 渉
    • Organizer
      日本農芸化学会 2020年度 福岡大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Fragment-based discovery of inhibitory compounds of bacterial proteases for the development of the novel antibiotics.2019

    • Author(s)
      Akihiro Nakamura, Yasumitsu Sakamoto, Yoshiyuki Suzuki, Saori Roppongi, Yosuke Shida, Koji Inaka, Hiroaki Tanaka, Kiyoito Kihira, Mitsugu Yamada, Izumi Yoshizaki, Hiroaki Gouda, Takamasa Nonaka, Nobutada Tanaka, Wataru Ogasawara
    • Organizer
      Tsukuba Conference 2019
    • Related Report
      2019 Annual Research Report
  • [Presentation] Fragment-based discovery of the first nonpeptidyl inhibitor of an S46 family peptidase2019

    • Author(s)
      Akihiro Nakamura, Yasumitsu Sakamoto, Yoshiyuki Suzuki, Saori Roppongi, Yosuke Shida, Koji Inaka, Hiroaki Tanaka, Kiyoito Kihira, Mitsugu Yamada, Izumi Yoshizaki, Hiroaki Gouda, Takamasa Nonaka, Nobutada Tanaka, Wataru Ogasawara
    • Organizer
      4th STI-Gigaku
    • Related Report
      2019 Annual Research Report
  • [Presentation] Stenotrophomonas maltophilia 由来Dipeptidyl peptidase 7の基質P2認識機構の解析2019

    • Author(s)
      中村 彰宏, 橋口 太一, 本間 宣行, 鈴木 義之, 阪本 泰光, 田中 信忠, 小笠原 渉
    • Organizer
      日本農芸化学会2019年度大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Structure comparisons of dipeptidyl aminopeptidase IV family2019

    • Author(s)
      六本木沙織, 鈴木義之, 館岡千佳, 藤本真友, 森澤さおり, 飯塚一平, 中村彰宏, 本間宣行, 伊藤康広, 志田洋介, 小笠原渉, 田中信忠, 阪本泰光, 野中孝昌
    • Organizer
      2018年度量子ビームサイエンスフェスタ
    • Related Report
      2018 Annual Research Report
  • [Presentation] エマルション培養法を用いた微生物由来ペプチダーゼスクリーニング系基盤構築に向けて2018

    • Author(s)
      本間 宣行, 中村 彰宏, 鈴木 義之, 志田 洋介, 野田 尚宏, 小笠原 渉
    • Organizer
      第70回日本生物工学会大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Elucidation of Substrate Recognition Mechanism of Dipeptidyl Aminopeptidase IV from Gram-negative Bacteria Pseudoxanthomonas mexicana WO242018

    • Author(s)
      Akihiro Nakamura, Nobuyuki Honma, Saori Roppongi, Yoshiyuki Suzuki, Yosuke Shida, Yasumitsu Sakamoto, Koji Inaka, Hiroaki Tanaka, Kiyoito Kihira, Mitsugu Yamada, Izumi Yoshioka, Hiroaki Gouda, Takamasa Nonaka, Nobutada Tanaka, and Wataru Ogasawara
    • Organizer
      The 7th International GIGAKU Conference
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Pseudoxanthomonas mexicana WO24由来Dipeptidyl aminopeptidase IVの基質認識機構の解明2018

    • Author(s)
      中村彰宏, 本間宣行, 六本木沙織, 鈴木義之, 志田洋介, 阪本泰光, 飯塚一平, 伊中浩治, 田仲広明, 木平清人 ,山田貢, 吉崎泉, 合田浩明, 野中孝昌, 田中信忠, 小笠原渉
    • Organizer
      日本農芸化学会2018年度大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 部位特異的変異導入解析によるFamily S46ペプチダーゼの基質認識残基の同定2018

    • Author(s)
      本間宣行, 中村彰宏, 六本木沙織, 鈴木義之, 志田洋介, 阪本泰光, 飯塚一平, 伊中浩治, 田仲広明, 木平清人, 山田貢, 吉崎泉, 合田浩明, 野中孝昌, 田中信忠, 小笠原渉
    • Organizer
      日本農芸化学会2018年度大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Identification of Substrate Recognition Residues in Family S46 Peptidase from Pathogenic Non-Fermenting Gram- Negative Bacteria2017

    • Author(s)
      Akihiro Nakamura, Yasuhiro Ito, Yoshiyuki Suzuki, Saori Roppogi, Koushi Hidaka, Yasumitsu Sakamoto, Nobutada Tanaka, Wataru Ogasawara
    • Organizer
      IUMS2017 SINGAPORE
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Identification of Substrate Recognition Residues in Family S46 Peptidase from Gram-Negative Bacteria2017

    • Author(s)
      Akihiro Nakamura, Yoshiyuki Suzuki, Saori Roppongi, Koushi Hidaka, Yasumitsu Sakamoto, Nobutada Tanaka, Wataru Ogasawara
    • Organizer
      The 6th International GIGAKU Conference
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 糸状菌 Trichoderma reesei における分泌プロテアーゼの生産応答機構の解析2017

    • Author(s)
      鈴木義之, Nayani Daranagama, 志田洋介, 森一樹, 油谷幸代, 小笠原渉
    • Organizer
      第17回糸状菌分子生物学コンファレンス
    • Related Report
      2017 Annual Research Report
  • [Presentation] WO24由来Dipeptidyl aminopeptidase IVの構造2017

    • Author(s)
      中村 彰宏, 本間 宣行, 六本木 沙織, 鈴木 義之, 志田 洋介, 阪本 泰光, 飯塚 一平, 伊中 浩治, 田中 広明, 木平 清人, 山田 貢, 吉崎 泉
    • Organizer
      第12回日本ゲノム微生物学会年会
    • Related Report
      2017 Annual Research Report
  • [Remarks] 長岡技術科学大学発酵科学研究室

    • URL

      http://www.microorganisms.jp/ogasawara-lab/

    • Related Report
      2020 Annual Research Report
  • [Remarks] 長岡技術科学大学生物機能工学専攻

    • URL

      http://bio.nagaokaut.ac.jp/

    • Related Report
      2020 Annual Research Report
  • [Remarks] 長岡技術科学大学技術科学イノベーション専攻

    • URL

      http://sti.nagaokaut.ac.jp/

    • Related Report
      2020 Annual Research Report
  • [Remarks] 長岡技術科学大学 生物機能工学専攻

    • URL

      http://bio.nagaokaut.ac.jp/

    • Related Report
      2019 Annual Research Report
  • [Remarks] 長岡技術科学大学 技術科学イノベーション専攻

    • URL

      http://sti.nagaokaut.ac.jp/index.html

    • Related Report
      2019 Annual Research Report
  • [Remarks] 長岡技術科学大学 小笠原研究室

    • URL

      http://www.microorganisms.jp/ogasawara-lab/

    • Related Report
      2019 Annual Research Report
  • [Remarks] INTERNATIONAL SPACE STATION BENEFITS FOR HUMANITY

    • URL

      https://www.nasa.gov/sites/default/files/atoms/files/benefits-for-humanity_third.pdf

    • Related Report
      2018 Annual Research Report
  • [Remarks] 長岡技術科学大学小笠原研究室

    • URL

      http://www.microorganisms.jp/ogasawara-lab/

    • Related Report
      2017 Annual Research Report
  • [Remarks] 発酵を科学する まだ見ぬ‘美’生物の世界~99%へのプロローグ~

    • URL

      http://www.microorganisms.jp/

    • Related Report
      2017 Annual Research Report
  • [Patent(Industrial Property Rights)] ペプチド型細菌ジペプチジルペプチダーゼ7阻害剤2018

    • Inventor(s)
      日高興士, 津田裕子, 阪本泰光, 小笠原 渉
    • Industrial Property Rights Holder
      日高興士, 津田裕子, 阪本泰光, 小笠原 渉
    • Industrial Property Rights Type
      特許
    • Filing Date
      2018
    • Related Report
      2018 Annual Research Report
  • [Patent(Industrial Property Rights)] ペプチド型細菌ジペプチジルペプチダーゼ7阻害剤2017

    • Inventor(s)
      柴田 望、小笠原 渉、志田 洋介
    • Industrial Property Rights Holder
      柴田 望、小笠原 渉、志田 洋介
    • Industrial Property Rights Type
      特許
    • Filing Date
      2017
    • Related Report
      2017 Annual Research Report
  • [Patent(Industrial Property Rights)] 改変プロモーター2017

    • Inventor(s)
      掛下 大視,柴田 望、小笠原 渉、志田 洋介
    • Industrial Property Rights Holder
      掛下 大視,柴田 望、小笠原 渉、志田 洋介
    • Industrial Property Rights Type
      特許
    • Filing Date
      2017
    • Related Report
      2017 Annual Research Report
  • [Patent(Industrial Property Rights)] 糸状菌変異株及びその利用2017

    • Inventor(s)
      柴田 望、小笠原 渉、志田 洋介
    • Industrial Property Rights Holder
      柴田 望、小笠原 渉、志田 洋介
    • Industrial Property Rights Type
      特許
    • Filing Date
      2017
    • Related Report
      2017 Annual Research Report
    • Overseas

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Published: 2017-04-28   Modified: 2022-01-27  

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