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Crystallographic analysis of an anticancer target enzyme at high resolution

Research Project

Project/Area Number 18K06600
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 47020:Pharmaceutical analytical chemistry and physicochemistry-related
Research InstitutionKumamoto University

Principal Investigator

Nakamura Teruya  熊本大学, 大学院先導機構, 准教授 (40433015)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords構造生物学 / X線結晶構造解析 / 中性子結晶構造解析
Outline of Final Research Achievements

In this research, we investigated mechanisms of an enzymatic reaction and inhibitor binding of an oxidized nucleotide hydrolase. We carried out the crystallization under microgravity and determined the high-resolution crystal structure. The structure revealed the protonation state in the active site with higher accuracy and precision. In addition, we obtained structural insights into the substrate specificity of the hydrolase by experiments of X-ray crystallography, activity measurement, and substrate binding.

Academic Significance and Societal Importance of the Research Achievements

酵素などのタンパク質の機能を原子レベルで理解するには、水素原子までをも明らかにする精密構造解析が必要不可欠である。本研究では、酸化ヌクレオチド加水分解酵素の精密構造解析を行うことで、酵素反応機構、阻害剤結合において重要な活性部位の水素原子を含めた構造情報を得た。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (14 results)

All 2021 2020 2019 2018

All Journal Article (7 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 7 results,  Open Access: 3 results) Presentation (7 results) (of which Int'l Joint Research: 1 results,  Invited: 4 results)

  • [Journal Article] RAD18 mediates DNA double-strand break-induced ubiquitination of chromatin protein2021

    • Author(s)
      Mustofa Md Kawsar、Tanoue Yuki、Chirifu Mami、Shimasaki Tatsuya、Tateishi Chie、Nakamura Teruya、Tateishi Satoshi
    • Journal Title

      The Journal of Biochemistry

      Volume: in press Issue: 1 Pages: 33-40

    • DOI

      10.1093/jb/mvab010

    • NAID

      40022722273

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Lactose-appended β-cyclodextrin as an effective nanocarrier for brain delivery2020

    • Author(s)
      Yokoyama Ryoma、Taharabaru Toru、Nishida Takumi、Ohno Yoshitaka、Maeda Yuki、Sato Masahiro、Ishikura Kandai、Yanagihara Kazunori、Takagi Hiroki、Nakamura Teruya、Ito Shingo、Ohtsuki Sumio、Arima Hidetoshi、Onodera Risako、Higashi Taishi、Motoyama Keiichi
    • Journal Title

      Journal of Controlled Release

      Volume: 328 Pages: 722-735

    • DOI

      10.1016/j.jconrel.2020.09.043

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A Conformational Escape Reaction of HIV-1 against an Allosteric Integrase Inhibitor2020

    • Author(s)
      Nakamura Tomofumi、Nakamura Teruya、Amano Masayuki、Miyakawa Toshikazu、Yamagata Yuriko、Matsuoka Masao、Nakata Hirotomo
    • Journal Title

      Journal of Virology

      Volume: 94 Issue: 19 Pages: 1-20

    • DOI

      10.1128/jvi.00486-20

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Structural analysis of TIFA: Insight into TIFA-dependent signal transduction in innate immunity2020

    • Author(s)
      Nakamura Teruya、Hashikawa Chie、Okabe Kohtaro、Yokote Yuya、Chirifu Mami、Toma-Fukai Sachiko、Nakamura Narushi、Matsuo Mihoko、Kamikariya Miho、Okamoto Yoshinari、Gohda Jin、Akiyama Taishin、Semba Kentaro、Ikemizu Shinji、Otsuka Masami、Inoue Jun-ichiro、Yamagata Yuriko
    • Journal Title

      Scientific Reports

      Volume: 10 Issue: 1 Pages: 5152-5152

    • DOI

      10.1038/s41598-020-61972-6

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] X-ray Structure Analysis of Human Oxidized Nucleotide Hydrolase MTH1 using Crystals Obtained under Microgravity2019

    • Author(s)
      Nakamura T, Hirata K, Fujimiya K, Chirifu M, Arimori T, Tamada T, Ikemizu S, Yamagata Y
    • Journal Title

      International journal of microgravity science and application

      Volume: 36 Issue: 1 Pages: 360103

    • DOI

      10.15011//jasma.36.360103

    • NAID

      130007769928

    • ISSN
      2188-9783
    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] SIRT7 has a critical role in bone formation by regulating lysine acylation of SP7/Osterix2018

    • Author(s)
      Fukuda Masatoshi、Yoshizawa Tatsuya et al.
    • Journal Title

      Nature Communications

      Volume: 9 Issue: 1 Pages: 2833-2833

    • DOI

      10.1038/s41467-018-05187-4

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Anammox Organism KSU-1 Expresses a Novel His/DOPA Ligated Cytochrome c2018

    • Author(s)
      Hira Daisuke、Kitamura Ryuji、Nakamura Teruya、Yamagata Yuriko、Furukawa Kenji、Fujii Takao
    • Journal Title

      Journal of Molecular Biology

      Volume: 430 Issue: 8 Pages: 1189-1200

    • DOI

      10.1016/j.jmb.2018.02.017

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Presentation] 自然免疫に関わるシグナル分子TIFAの構造学的研究2020

    • Author(s)
      中村照也
    • Organizer
      日本結晶学会 令和2年度年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 酵素の基質特異性に関わる水素原子の観察2020

    • Author(s)
      中村照也
    • Organizer
      CBI学会 2020年大会
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 酵素の精密構造解析 抗がん剤標的分子の基質認識における水素原子の役割2019

    • Author(s)
      中村 照也
    • Organizer
      日本プロテオーム学会 2019年大会・第70回日本電気泳動学会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] ヒト酸化ヌクレオチド加水分解酵素の新規基質の同定2019

    • Author(s)
      藤宮 佳菜、中村 照也、平田 啓介、池鯉鮒 麻美、池水 信二、山縣 ゆり子
    • Organizer
      第43回 蛋白質と酵素の構造と機能に関する九州シンポジウム
    • Related Report
      2019 Research-status Report
  • [Presentation] ゲノム安定性維持機構の構造生物学2019

    • Author(s)
      中村 照也
    • Organizer
      第2回熊本大学ライフサイエンスシーズ探索研究会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] Crystal structure of human oxidative nucleotide hydrolase in complex with a newly found substrate2018

    • Author(s)
      Teruya Nakamura
    • Organizer
      第56回日本生物物理学会年会
    • Related Report
      2018 Research-status Report
  • [Presentation] ヒト酸化ヌクレオチド加水分解酵素の構造学的研究-水素原子レベルでの酵素反応機構の解明を目指して-2018

    • Author(s)
      中村 照也
    • Organizer
      平成30年度iBIX-JAXA-KEK物構研-QST合同タンパク質研究会
    • Related Report
      2018 Research-status Report
    • Invited

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Published: 2018-04-23   Modified: 2022-01-27  

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