• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

The studies of reaction mechanism of cyanide-insensitive alternative oxidase from Trypanosoma brucei (TAO), a promising drug target

Research Project

Project/Area Number 23570131
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Structural biochemistry
Research InstitutionKyoto Institute of Technology

Principal Investigator

SHIBA Tomoo  京都工芸繊維大学, 工芸科学研究科, 准教授 (80401206)

Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2011: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywordsトリパノソーマ / diironタンパク質 / 膜表在型タンパク質 / アスコフラノン / X線結晶構造解析
Research Abstract

Trypanosoma brucei is the causative agent of human African sleeping sickness (trypanosomiasis). The cyanide-insensitive alternative oxidase from T. brucei (TAO) is a membrane-bound diiron carboxylate protein which is located on the inner surface of the inner mitochondrial membrane Since TAO is absent from the mammalian host it is a promising target for the development of anti-trypanosomal drugs.
I have reported on the first crystal structure of TAO in the presence and absence of an ascofuranone (AF)-derivative at 2.6 and 2.85 angstrom resolution, respectively (Shiba T et al. Proc. Natl. Acad. Sci. USA, 2013). The structures reveal a membrane binding region and an active-site containing 4 glutamate and 2 histidine residues which are buried in a 4-helix bundle. The binding of the AF-inhibitor results in major conformational changes at the active site.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • 2011 Research-status Report
  • Research Products

    (33 results)

All 2014 2013 2012 2011 Other

All Journal Article (16 results) (of which Peer Reviewed: 16 results) Presentation (15 results) Remarks (2 results)

  • [Journal Article] 希少疾病のアカデミア創薬–グローバルオーファンドラッグ創成をめざして–2014

    • Author(s)
      北潔, 志波智生, 原田繁春
    • Journal Title

      実験医学増刊

      Volume: 32(2) Pages: 210-215

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Anemia amelioration by lactose infusion during trypanosomosis could be associated with erythrocytes membrane de-galactosylation2014

    • Author(s)
      Balogun EO, Balogun JAB, Yusuf S, Inuwa HM, Ndams IS, Sheridan P, Inaoka DK, Shiba T, Harada S, Kita K, Esievo KAN, Nok AJ.
    • Journal Title

      Veterinary Parasitology

      Volume: 199 Pages: 259-263

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] 希少疾病のアカデミア創薬 – グローバルオーファンドラッグ創成をめざして –2014

    • Author(s)
      北潔, 志波智生, 原田繁春
    • Journal Title

      実験医学増刊

      Volume: 32 Pages: 210-215

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The alternative oxidases : simple oxidoreductase proteins with complex functions2013

    • Author(s)
      Young L, Shiba T, Harada S, Kita K, Albury MS, Moore AL.
    • Journal Title

      Biochem Soc Trans.

      Volume: 41 Pages: 1305-1311

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Biochemical characterization of highly active Trypanosoma brucei gambiense glycerol kinase, a promising drug target2013

    • Author(s)
      Balogun EO, Inaoka DK, Shiba T, Kido Y, Nara T, Aoki T, Honma T, Tanaka A, Inoue M, Matsuoka S, Michels PA, Harada S, Kita K.
    • Journal Title

      J. Biochemistry

      Volume: 154 Pages: 77-84

    • NAID

      40019683344

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] アフリカ睡眠病治療薬の候補化合物と標的タンパク質との複合体構造2013

    • Author(s)
      志波智生, 高橋元, 原田繁春, 斎本博之, 城戸康年, 稲岡ダニエル健, 北潔.
    • Journal Title

      日本結晶学会誌

      Volume: 55 Pages: 254-259

    • NAID

      10031194726

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Unraveling the heater : new insights into the structure of the alternative oxidase2013

    • Author(s)
      Moore AL, Shiba T, Young L, Harada S, Kita K, Ito K.
    • Journal Title

      Annu. Rev Plant Biol.

      Volume: 64 Pages: 637-663

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Structure of the trypanosome cyanide-insensitive alternative oxidase2013

    • Author(s)
      Shiba T, Kido Y, Sakamoto K, Inaoka DK, Tsuge C, Tatsumi R, Takahashi G, Balogun EO, Nara T, Aoki T, Honma T, Tanaka A, Inoue M, Matsuoka S, Saimoto H, Moore AL, Harada S, Kita K.
    • Journal Title

      Proc. Natl. Acad. Sci. USA

      Volume: 110 Pages: 4580-4585

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Identification and characterization of sialidase-like activity in the developmental stages of Amblyomma variegatum2013

    • Author(s)
      Natala AJ, Balogun EO, Balogun JA, Inuwa HM, Nok AJ, Shiba T, Harada S, Kita K, Agbede RI, Esievo KA.
    • Journal Title

      J. of Med. Entomol.

      Volume: 50 Pages: 85-93

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Structures of cyanobacteriochromes from phototaxis regulators AnPixJ and TePixJ reveal general and specific photoconversion mechanism2013

    • Author(s)
      Narikawa R, Ishizuka T, Muraki N, Shiba T, Kurisu G, Ikeuchi M.
    • Journal Title

      Proc. Natl. Acad. Sci. USA

      Volume: 110 Pages: 918-923

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Unraveling the Heater: New Insights into the Structure of the Alternative Oxidase2013

    • Author(s)
      Anthony L. Moore, Tomoo Shiba, Luke Young, Shigeharu Harada, Kiyoshi Kita, Kikukatsu Ito
    • Journal Title

      Annual Review of Plant Biology

      Volume: 64 Issue: 1 Pages: 637-663

    • DOI

      10.1146/annurev-arplant-042811-105432

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The alternative oxidases: simple oxidoreductase proteins with complex functions2013

    • Author(s)
      Luke Young, Tomoo Shiba, Shigeharu Harada, Kiyoshi Kita, Mary S. Albury, Anthony L. Moore
    • Journal Title

      Biochem. Soc. Trans.

      Volume: 41 Issue: 5 Pages: 1305-1311

    • DOI

      10.1042/bst20130073

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Identification and Characterization of Sialidase-Like Activity in the Developmental Stages of Amblyomma Variegatum2013

    • Author(s)
      Audu J. Natala, Emmanuel 0. Balogun, Joshua A. B. Balogun, Hajiya M. Inuwa, Andrew J. Nok, Tomoo Shiba, Shigeharu Harada,Kiyoshi Kita, Rowland l. S. Agbede, King A. N. Esievo
    • Journal Title

      Journal of Medical Entomology

      Volume: 50 (1) Issue: 1 Pages: 85-93

    • DOI

      10.1603/me12152

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] The role of amino acid residues in the active site of L-methionineγ-lyase from Pseudomonas putida2012

    • Author(s)
      Fukumoto M, Kudou D, Murano S, Shiba T, Sato D, Tamura T, Harada S, Inagaki K.
    • Journal Title

      Biosci. Biotechnol. Biochem.

      Volume: 76

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Crystal structure of mitochondrial quinol-fumarate reductase from the parasitic nematode Ascaris suum2012

    • Author(s)
      Shimizu H, Osanai A, Sakamoto K, Inaoka DK, Shiba T, Harada S, Kita K.
    • Journal Title

      J. Biochemistry

      Volume: 151

    • NAID

      10031166100

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] The Role of Amino Acid Residues in the Active Site of <small>L</small>-Methionine &#947;-lyase from <i>Pseudomonas putida</i>2012

    • Author(s)
      Fukumoto, M.
    • Journal Title

      Bioscience, Biotechnology, and Biochemistry

      Volume: 76 Issue: 7 Pages: 1275-1284

    • DOI

      10.1271/bbb.110906

    • NAID

      130001862713

    • ISSN
      0916-8451, 1347-6947
    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] アフリカトリパノソーマのシアン耐性酸化酵素(TAO)と新規阻害剤:フェルレノールとの複合体の結晶構造2013

    • Author(s)
      高橋元, 志波智生, 上田慧, 稲岡ダニエル健, 城戸康年, 坂元君年, 柘植千明, Balogun EO, 奈良武司, 青木孝, 本間光貴, 田仲昭子, 井上将行, 松岡茂, Moore AL, 斎本博之, 原田繁春, 北潔
    • Organizer
      第86回日本生化学会大会
    • Place of Presentation
      横浜
    • Related Report
      2013 Final Research Report
  • [Presentation] アフリカトリパノソーマの薬剤標的「シアン耐性酸化酵素Trypanosome Alternative Oxidase (TAO)」の結晶構造解析2013

    • Author(s)
      志波智生, 高橋元, 城戸康年, 稲岡ダニエル健, 坂元君年, 柘植千明, 辰巳涼子, Balogun EO, 奈良武司, 青木孝, 本間光貴, 田仲昭子, 井上将行, 松岡茂, Moore AL, 斎本博之, 原田繁春, 北潔
    • Organizer
      第86回日本生化学会大会
    • Place of Presentation
      横浜
    • Related Report
      2013 Final Research Report
  • [Presentation] The search for inhibitors of African trypanosomes glycerol kinase2013

    • Author(s)
      Balogun EO, Inaoka DK, Shiba T, Kido Y, Nara T, Aoki T, Honma T, Tanaka A, Inoue M, Matsuoka S, Michels PA, Kita K, Harada S.
    • Organizer
      第13回日本蛋白質科学会年会
    • Place of Presentation
      鳥取
    • Related Report
      2013 Final Research Report
  • [Presentation] シアン耐性酸化酵素Trypanosome Alternative Oxidase(TAO)の結晶構造2013

    • Author(s)
      志波智生, 城戸康年, 高橋元, 稲岡ダニエル健, 坂元君年, 奈良武司, 青木孝, 本間光貴, 田仲昭子, 井上将行, 松岡茂, 斎本博之, 原田繁春, 北潔
    • Organizer
      第13回日本蛋白質科学会年会
    • Place of Presentation
      鳥取
    • Related Report
      2013 Final Research Report
  • [Presentation] アフリカトリパノソーマの薬剤標的「シアン耐性酸化酵素Trypanosome Alternative Oxidase (TAO)」の結晶構造解析2013

    • Author(s)
      志波智生、高橋元、城戸康年、稲岡ダニエル健、坂元君年、柘植千明、辰巳涼子、Emmanuel Oluwadare Balogun、奈良武司、青木孝、本間光貴、田仲昭子、井上将行、松岡茂、Anthony L. Moore、斎本博之、原田繁春、北潔
    • Organizer
      第86会日本生化学会
    • Place of Presentation
      横浜
    • Related Report
      2013 Annual Research Report
  • [Presentation] アフリカトリパノソーマのシアン耐性酸化酵素 (TAO)と新規阻害剤: フェルレノールとの複合体の結晶構造2013

    • Author(s)
      高橋 元, 志波 智生, 上田 慧, 稲岡 ダニエル健, 城戸 康年, 坂元 君年, 柘植 千明, Oluwadare Balogun Emmanuel, 奈良 武司, 青木 孝, 本間 光貴, 田仲 昭子, 井上 将行, 松岡 茂, L. Moore Anthony, 斎本 博之, 原田 繁春, 北 潔
    • Organizer
      第86会日本生化学会
    • Place of Presentation
      横浜
    • Related Report
      2013 Annual Research Report
  • [Presentation] アフリカトリパノソーマ症の薬剤標的「シアン耐性酸化酵素Trypanosome Alternative Oxidase (TAO)」の精製と結晶構造解析2012

    • Author(s)
      高橋元, 志波智生, 城戸康年, 稲岡ダニエル健, 坂元君年, 奈良武司, 青木孝, 本間光貴, 田仲昭子, 井上将行, 松岡茂, Moore AL, 斎本博之, 原田繁春, 北潔
    • Organizer
      第85回日本生化学会
    • Place of Presentation
      福岡
    • Related Report
      2013 Final Research Report
  • [Presentation] Structure-based approach for developing trypanosome-specific glycerol kinase inhibitor(s)2012

    • Author(s)
      Balogun EO, Inaoka DK, Shiba T, Kido Y, Nara T, Aoki T, Honma T, Tanaka A, Inoue M, Matsuoka S, Michels PA, Harada S, Kita K.
    • Organizer
      第12回日本蛋白質科学会年会
    • Place of Presentation
      名古屋
    • Related Report
      2013 Final Research Report
  • [Presentation] アフリカトリパノソーマの薬剤標的「シアン耐性酸化酵素Trypanosome Alternative Oxidase(TAO)」の結晶構造2012

    • Author(s)
      志波智生, 城戸康年, 稲岡ダニエル健, 坂元君年, 奈良武司, 青木孝, 本間光貴, 田仲昭子, 井上将行, 松岡茂, Moore AL, 斎本博之, 原田繁春, 北潔
    • Organizer
      第12回日本蛋白質科学会年会
    • Place of Presentation
      名古屋
    • Related Report
      2013 Final Research Report
  • [Presentation] アフリカトリパノソーマの薬剤標的「シアン耐性酸化酵素Trypanosome Alternative Oxidase(TAO)」の結晶構造2012

    • Author(s)
      志波 智生、城戸 康年、稲岡 ダニエル健、坂元 君年、奈良 武司、青木 孝、本間 光貴、田仲 昭子、井上 将行、松岡 茂、ムーア アンソニィー、斎本 博之、原田 繁春、北 潔
    • Organizer
      日本蛋白質科学会年会
    • Place of Presentation
      名古屋
    • Related Report
      2012 Research-status Report
  • [Presentation] アフリカトリパノソーマ症の薬剤標的「シアン耐性酸化酵素Trypanosome Alternative Oxidase (TAO)」の精製と結晶構造解析2012

    • Author(s)
      高橋 元、志波 智生、城戸 康年、ダニエル健 稲岡、坂元 君年、奈良 武司、青木 孝、本間 光貴、田仲 昭子、井上 将行、松岡 茂、Moore Anthony、斎本 博之、原田 繁春、北 潔
    • Organizer
      日本生化学会
    • Place of Presentation
      福岡
    • Related Report
      2012 Research-status Report
  • [Presentation] Structural analysis of glycerol kinase from human African trypanosomes for anti-trypanosomal drug design2011

    • Author(s)
      Balogun EO, 稲岡ダニエル健, 志波智生, 城戸康年, 奈良武司, 青木孝, 本間光貴, 田仲昭子, 井上将行, 松岡茂, Michels PA, 原田繁春, 北潔
    • Organizer
      第84回日本生化学会大会
    • Place of Presentation
      京都
    • Related Report
      2013 Final Research Report
  • [Presentation] トリパノソーマ原虫のミトコンドリアの内膜に局在する「シアン耐性酸化酵素Trypanosome Alternative Oxidase (TAO)」の結晶構造」2011

    • Author(s)
      志波智生, 城戸康年, 稲岡ダニエル健, 坂元君年, 奈良武司, 青木孝, 本間光貴, 田仲昭子, 井上将行, 松岡茂, 斎本博之, Moore AL, 原田繁春, 北潔
    • Organizer
      第84回日本生化学会大会
    • Place of Presentation
      京都
    • Related Report
      2013 Final Research Report
  • [Presentation] アフリカトリパノソーマの薬剤標的「シアン耐性酸化酵素Trypanosome Alternative Oxidase (TAO)」の結晶構造2011

    • Author(s)
      志波智生
    • Organizer
      日本結晶学会年会
    • Place of Presentation
      北海道大学
    • Related Report
      2011 Research-status Report
  • [Presentation] トリパノソーマ原虫のミトコンドリアの内膜に局在する「シアン耐性酸化酵素Trypanosome Alternative Oxidase (TAO)」の結晶構造2011

    • Author(s)
      志波智生
    • Organizer
      日本生化学会大会
    • Place of Presentation
      国立京都国際会議場
    • Related Report
      2011 Research-status Report
  • [Remarks]

    • URL

      http://www.kit.ac.jp/01/topics/2012/pressrelease130305.html

    • Related Report
      2013 Final Research Report
  • [Remarks] アフリカ睡眠病治療薬の候補化合物と標的タンパク質との複合体構造の解明

    • URL

      http://www.kit.ac.jp/01/topics/2012/pressrelease130305.pdf

    • Related Report
      2012 Research-status Report

URL: 

Published: 2011-08-05   Modified: 2019-07-29  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi