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Analysis of NAD metabolic pathway in Mycobacterium tuberculosis and elucidation of its compensatory pathway

Research Project

Project/Area Number 15K07377
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Applied microbiology
Research InstitutionNational Institute of Infectious Diseases

Principal Investigator

MORI Shigetarou  国立感染症研究所, 細菌第二部, 室長 (60425676)

Project Period (FY) 2015-10-21 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords結核菌 / タンパク質 / 酵素 / ドッキングシミュレーション / NAD生合成 / タンパク質発現 / 立体構造解析 / NAD合成経路
Outline of Final Research Achievements

In this research project, we mainly analyzed the functions and structures of mycobacterial enzymes involved in the NAD biosynthetic pathway. The optimal conditions for expressing Rv0212c, Rv1901c, Rv3199c, and Rv3393 of Mycobacterium tuberculosis in Escherichia coli were determined. We found that Rv3393 shows nucleoside hydrolysis activity. In addition, we showed that the structure of the substrate-binding site of phosphoribosyl diphosphate synthase from M. smegmatis differs from that of human phosphoribosyl diphosphate synthase. Furthermore, the enzymatic properties of Rv3257c and Rv3308 from M. tuberculosis and the three-dimensional structure of the nucleotide phosphorylase from M. avium were determined in detail.

Report

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

    (6 results)

All 2017 2016 2015

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

  • [Journal Article] Biochemical and structural investigations on phosphoribosylpyrophosphate synthetase from Mycobacterium smegmatis2017

    • Author(s)
      Donini Stefano、Garavaglia Silvia、Ferraris Davide M.、Miggiano Riccardo、Mori Shigetarou、Shibayama Keigo、Rizzi Menico
    • Journal Title

      PLOS ONE

      Volume: 12 Issue: 4 Pages: e0175815-e0175815

    • DOI

      10.1371/journal.pone.0175815

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Purification and functional characterization of diadenosine 5', 5'''-P1,P4-tetraphosphate phosphorylases from Mycobacterium smegmatis and Mycobacterium avium.2015

    • Author(s)
      Naoko Honda, Hyun Kim, Emiko Rimbara, Atsushi Kato, Keigo Shibayama, Shigetarou Mori
    • Journal Title

      Protein Expression and Purification

      Volume: 112 Pages: 37-42

    • DOI

      10.1016/j.pep.2015.04.010

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 結核菌由来diadenosine tetraphosphate加リン酸分解酵素の新規阻害剤と抗結核菌活性2017

    • Author(s)
      森茂太郎、本田尚子、金玄、林原絵美子、柴山恵吾
    • Organizer
      日本農芸化学会2017年度大会
    • Place of Presentation
      京都
    • Year and Date
      2017-03-18
    • Related Report
      2016 Research-status Report
  • [Presentation] Molecular characterization of a nicotinate phosphoribosyltransferase from Mycobacterium tuberculosis H37Rv2017

    • Author(s)
      Shigetarou Mori, Hyun Kim, Emiko Rimbara, Keigo Shibayama
    • Organizer
      US-Japan Cooperative Medical Science Program: Mycobacterial Panel Meeting
    • Place of Presentation
      韓国・ソウル
    • Year and Date
      2017-02-09
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] The development of novel structure based inhibitors of diadenosine phosphorylase from Mycobacterium tuberculosis2017

    • Author(s)
      森茂太郎, 本田尚子, 金玄, 林原絵美子, 柴山恵吾
    • Organizer
      International Union of Microbiological Societies Congresses 2017
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Novel inhibitors of diadenosine tetraphosphate phosphorylase and their antituberculosis activity2016

    • Author(s)
      Shigetarou Mori, Naoko Honda, Hyun Kim, Emiko Rimbara, and Keigo Shibayama
    • Organizer
      第89回日本細菌学会総会
    • Place of Presentation
      大阪市
    • Year and Date
      2016-03-23
    • Related Report
      2015 Research-status Report

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Published: 2015-10-21   Modified: 2019-03-29  

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