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The identification of the factor about intracellular parasitism of Mycobacterium tuberculosis and the development of the control method

Research Project

Project/Area Number 24780088
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
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) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2012: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Keywords結核菌 / X線結晶構造解析 / 非結核性抗酸菌 / 加リン酸分解酵素 / ドラッグデザイン / 新規抗結核薬 / ヌクレオチド / 抗酸菌 / 加リン酸分解 / インシリコスクリーニング
Outline of Final Research Achievements

It was revealed that the flexibility of a loop, which is located in the active site of diadenosine tetraphosphate phosphorylase from Mycobacterium tuberculosis (MtAPA), might be correlated with substrate specificity of MtAPA. Based on the results of the structure-function analysis of MtAPA, new inhibitors of MtAPA were found. Moreover, it was showed that the MtAPA homologous proteins from M. avium and M. smegmatis possess diadenosine tetraphosphate phosphorylase activities and that the new inhibitors of MtAPA could inhibit the activities of these proteins. On the other hand, it was revealed that Rv2614c protein from M. tuberculosis is an aminoacyl-tRNA synthetase. It was expected that the results in this study would be valuable in elucidating the mechanism of intracellular parasitism of M. tuberculosis and developing the new anti-tuberculosis drugs.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (10 results)

All 2015 2014 2013

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 3 results,  Acknowledgement Compliant: 1 results) Presentation (7 results)

  • [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
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Roles of Ala-149 in the catalytic activity of diadenosine tetraphosphate phosphorylase from Mycobacterium tuberculosis H37Rv2014

    • Author(s)
      Mori S, Kim H, Rimbara E, Arakawa Y, Shibayama K
    • Journal Title

      Biosci Biotechnol Biochem

      Volume: 79 Issue: 2 Pages: 236-238

    • DOI

      10.1080/09168451.2014.973364

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Biochemical characterization of quinolinic acid phosphoribosyltransferase from Mycobacterium tuberculosis H37Rv and inhibition of its activity by pyrazinamide2014

    • Author(s)
      Kim H, Shibayama K, Rimbara E, Mori S
    • Journal Title

      PLoS One

      Volume: 9 Issue: 6 Pages: 1-11

    • DOI

      10.1371/journal.pone.0100062

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] Molecular characterization of nicotinate phosphoribosyltransferase from Mycobacterium tuberculosis H37Rv, and inhibition of its activity by pyrazinoic acid2014

    • Author(s)
      Shigetarou Mori, Hyun Kim, Emiko Rimbara, Yoshichika Arakawa, Keigo Shibayama
    • Organizer
      FEBS EMBO 2014
    • Place of Presentation
      フランス・パリ
    • Year and Date
      2014-08-30 – 2014-09-04
    • Related Report
      2014 Annual Research Report
  • [Presentation] Functions and structures of MAV_3489 from Mycobacterium avium and MSMEG_2932 from M. smegmatis2014

    • Author(s)
      森茂太郎, 金玄, 林原絵美子, 柴山恵吾
    • Organizer
      第87回日本細菌 学会総会
    • Place of Presentation
      東京
    • Related Report
      2013 Research-status Report
  • [Presentation] Structural insights into a diadenosine tetraphosphate phosphorylase from Mycobacterium tuberculosis H37Rv for the design of new anti-tuberculosis drugs2013

    • Author(s)
      森茂太郎, 金玄, 林原絵美子, 柴山恵吾
    • Organizer
      7th International Conference on Structural Genomics
    • Place of Presentation
      札幌
    • Related Report
      2013 Research-status Report
  • [Presentation] Structural insights into a novel diadenosine tetraphosphate phosphorylase from Mycobacterium tuberculosis2013

    • Author(s)
      森茂太郎, 金玄, 林原絵美子, 柴山恵吾
    • Organizer
      US-Japan Cooperative Medical Science Program: Tuberculosis and Leprosy Panel Meeting in Japan
    • Place of Presentation
      札幌
    • Related Report
      2013 Research-status Report
  • [Presentation] Structural insights into a novel diadenosine tetraphosphate phosphorylase from Mycobacterium tuberculosis2013

    • Author(s)
      森茂太郎, 金玄, 林原絵美子, 柴山恵吾
    • Organizer
      The 10th Japan-Taiwan Symposium on Vaccine Preventable Diseases and Vector-Borne Diseases
    • Place of Presentation
      東京
    • Related Report
      2013 Research-status Report
  • [Presentation] 結核菌由来ニコチン酸ホスホリボシルトランスフェラーゼの機能解析2013

    • Author(s)
      森 茂太郎、金 玄、林原 絵美子、荒川 宜親、柴山 恵吾
    • Organizer
      第86回日本細菌学会総会
    • Place of Presentation
      幕張メッセ(千葉市)
    • Related Report
      2012 Research-status Report
  • [Presentation] Mycobacterium avium由来MAV_3489とM. smegmatis由来MSMEG_2932の機能解析2013

    • Author(s)
      森 茂太郎、金 玄、林原 絵美子、柴山 恵吾
    • Organizer
      日本農芸化学会2013年度大会
    • Place of Presentation
      東北大学(仙台市)
    • Related Report
      2012 Research-status Report

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Published: 2013-05-31   Modified: 2019-07-29  

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