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Biosyrdiesis of iron-sulfur proteins in Enlanoeba histotyrica

Research Project

Project/Area Number 16017302
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionGunma University (2005)
Kyoto Pharmaceutical University (2004)

Principal Investigator

NOZAKI Tomoyoshi (2005)  Gunma Univer, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (60198588)

木曽 良明  京都薬科大学, 薬学部, 教授 (40089107)

Co-Investigator(Kenkyū-buntansha) ALI Vahab  Gunma University, Graduate School of Medicine, Research Associate, 大学院・医学系研究科, 助手 (20400757)
TAKAHASHI Yasuhiro  Osaka University, Graduate School of Science, Assistant Professor, 大学院・理学系研究科, 講師 (10154874)
木村 徹  京都薬科大学, 薬学部, 助手 (70204980)
Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥10,200,000 (Direct Cost: ¥10,200,000)
Fiscal Year 2005: ¥5,100,000 (Direct Cost: ¥5,100,000)
Fiscal Year 2004: ¥5,100,000 (Direct Cost: ¥5,100,000)
KeywordsEntamoeba histolytica / Parasitism / Electron transport / Iron sulfur cluster / Antioxidation / Enemy metabolism / 酵素阻害剤 / アスパラギン酸プロテアーゼ / HIVプロテアーゼ / マラリア / 基質遷移状態 / プラスメプシン / ドラッグデザイン / AIDS / 基質遷移状態誘導体
Research Abstract

Iron clusters are well conserved among all living organisms, and play a pivotal role in respiration, electron transport, redox, and nitrogen tetion. In this study, we aimed at molecular characterization of iron sulfur biosynthesis in Entamoeba histolytica, and understanding of its role in parasitism and pathogenesis. We also aimed at obtaining a Mole view of cysteine and serine biosynthesis in the parasite. Iron-sulfur biosynthesis is known to be catalyzed by one or more of three independent pathways : NIF, ISC, and SUF, depending upon organisms. E histolytica exclusively possesses components for the NIF pathway, namely the catalytic component NifS and the scaffold component NifU. The presence of the NIF system in eukaryotes is unprecedented. We showed that the amebic NIF system is capable of all kinds of iron sulfur dusters, functionally replace the function of ISC and SUF in a heterologous organism, and function only under anaerobic conditions. We also showed the NIF system is localized to the cytosol, which is in good contrast to ISC and SUF, localized to the mitochondria and chloroplast, respectively. We also showed that E. histolytica possesses two pathways for serine metabolism, namely phosphorylated and non-phosphorylated pathways, which seems to be involved in biosynthesis aid gluconeogenesis, respectively. The presence of both the serine pathways is unique to this organism among parasitic protists. The present study should help our understanding of physiological importance of iron duster biosynthesis and serine/cysteine metaboism in parasitic organisms.

Report

(3 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • Research Products

    (25 results)

All 2006 2005 2004 2003 Other

All Journal Article (24 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Evidence for the cellular uptake of anti-HIV-1 double drug KNI-10392006

    • Author(s)
      Sharad Mohan
    • Journal Title

      Bull.Osaka Med.Coll 51(2)

      Pages: 50-60

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Overcoming roadblocks in lead optimization : a thermodynamic perspective.2006

    • Author(s)
      Adam J.Ruben
    • Journal Title

      Chem.Biol.Drug.Des. 67(1)

      Pages: 2-4

    • Related Report
      2005 Annual Research Report
  • [Journal Article] X-ray crystal structure of the aspartic protease plasmepsin 4 from the malarial parasite Plasmodium malariae bound to an allophenylnorstatine based inhibitor.2006

    • Author(s)
      Jose Clemente
    • Journal Title

      Acta Crystallographica D 62(3)

      Pages: 246-252

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Evaluation of peptidomimetic HTLV-1 protease inhibitors containing hydroxymethylcarbonyl as a transition-state isostere.2006

    • Author(s)
      Ayako Itami
    • Journal Title

      Peptide Science 2005(in press)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Sulfur-containing amino acid metabolism in parasitic protozoa.2005

    • Author(s)
      Nozaki, T., Ali, V., Tokoro, M.
    • Journal Title

      Adv. Parasitol. 60

      Pages: 1-99

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Biochemical and functional characterization of phosphoserine aminotransferase from Ent ameba histolytica, which possesses both phosphorylated and non-phosphorylated serine metabolic pathways.2005

    • Author(s)
      Ali, V., Nozaki, T.
    • Journal Title

      Mol. Biochem. Parasitol. 145

      Pages: 71-83

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] The genome of the protist parasite Entamoeba histolytica.2005

    • Author(s)
      Loftus, B., et al.
    • Journal Title

      Nature 433

      Pages: 865-868

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] α-ヒドロキシ-β-アミノ酸を基盤とした有機化学・創薬化学研究2005

    • Author(s)
      林良雄
    • Journal Title

      有機合成化学協会誌 63(6)

      Pages: 640-651

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Establishment of a biological assay system for human retroviral protease activity.2005

    • Author(s)
      Akiko Yoshida
    • Journal Title

      Microbes and Infection 7(5/6)

      Pages: 820-824

    • Related Report
      2005 Annual Research Report
  • [Journal Article] An intestinal parasitic protist Entamoeba histolytica possesses a non-redundant NIF-like system for iron-sulfur cluster assembly under anaerobic conditions.2004

    • Author(s)
      Ali, V., Shigeta, Y., Tokumoto, U., Takahashi, Y., Nozaki, T.
    • Journal Title

      J. Biol. Chem. 179, 16863-16874. 279

      Pages: 16863-16874

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] (2004) Molecular and biochemical characterization of D-phosphoglycerate dehydrogenase from Entamoeba histolytica : a unique enteric protozoan parasite that possesses both phosphorylated and non-phosphorylated serine metabolic pathways.2004

    • Author(s)
      Ali, V., Shigeta, Y., Hashimoto, T., Nozaki, T.
    • Journal Title

      Eur. J. Biochem. 271, 2670-2681. 271

      Pages: 2670-2681

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] A new polymer-supported Evans-type chiral auxiliary derived from α-hydroxy-β-amino acid, phenylnorstatine.2004

    • Author(s)
      Tomoya Kotake
    • Journal Title

      Tetrahedron Letters 45(18)

      Pages: 3651-3654

    • Related Report
      2004 Annual Research Report
  • [Journal Article] A structural and thermodynamic escape mechanism from a drug resistant mutation of the HIV-1 protease.2004

    • Author(s)
      Sonia Vega
    • Journal Title

      Proteins : Str., Funct. & Bioinformatics 55(3)

      Pages: 594-602

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Identification of peptidomimetic HTLV-1 protease inhibitors containing hydroxymethylcarbonyl (HMC) isostere as the transition-state mimic.2004

    • Author(s)
      Hikoichiro Maegawa
    • Journal Title

      Bioorganic Medicinal Chemistry Letters 14(23)

      Pages: 5925-5929

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Search for substrate-based inhibitors fitting the S2' space of malarial aspartic protease plasmepsin II.2004

    • Author(s)
      Aiko Kiso
    • Journal Title

      Journal of Peptide Science 10(11)

      Pages: 641-647

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Design of inhibitors against HIV, HTLV-I, and Plasmodium falciparum aspartic proteases.2004

    • Author(s)
      Hamdy M.Abdel-Rahman
    • Journal Title

      Biological Chemsitry 385(1)

      Pages: 1035-1039

    • Related Report
      2004 Annual Research Report
  • [Journal Article] A novel dipeptide-based HIV protease inhibitor containing allophenylnorstatine.2004

    • Author(s)
      Hamdy M.Abdel-Rahman
    • Journal Title

      Arch.Pharm.Pharm.Med.Chem. 337(11)

      Pages: 587-598

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Molecular and structural characterization of NADPH-dependent D-glycerate dehydrogenase from the enteric parasitic protist Entamoeba histolytica.2003

    • Author(s)
      Ali, V., Shigeta, Y., Nozaki, T.
    • Journal Title

      Biochem. J. 375 : 729-736 375

      Pages: 729-736

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] (2005) Sulfur-containing amino acid metabolism in parasitic protozoa.

    • Author(s)
      Nozaki, T., AN, V., Tokoro, M.
    • Journal Title

      (Review) Adv. Parasitol. 60

      Pages: 1-100

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] (2006) Biochemical and functional characterization of phosphoserine aminotransferase from Entameba histolytica, which possesses both phosphorylated and non-phosphorylated serine metabolic pathways.

    • Author(s)
      Ali, V., Nozaki.T.
    • Journal Title

      Mol. Biochem. Parasitol. 145

      Pages: 71-83

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] (2005). The genome of the protist parasite Entamoeba histolytica.

    • Author(s)
      Loftus, B., Anderson, I., Davies, R., Alismark, U.C.M., Samuelson, J., Amedeo, P., Roncaglia, P., Berriman, M., Hirt, R.P., Mann, B.J., Nozaki, T., Suh, B., Pop, M., Duchene, M., Ackers, J., Tannich, E., Leippe, M., Hofer, M., Bruchhaus, I., Willhoeft, U., Bhattacharya, A., Chillingworth, TV, Churcher, C., Hance, Z., Harris, B., Harris, d., Jagels, K., Moule, S., Mungall, K., Ormond, D., Squares, R., Whitehead, S., Guillen, N., Gilchrist, C., Stroup, S.E., Bhattacharya, S., Lohia, A., Foster, P.G., Sicheritz-Ponten, T., Weber, C., Singh, U., Mukherjee, C., Petri, W.A.J., Clark, C.G., Embley, T.M., Barrell, B., Fraser, C.M., Hall, N.
    • Journal Title

      Nature 433

      Pages: 865-868

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] (2004) An intestinal parasitic protist, Entamoeba histolytica, possesses a non-redundant nitrogen fixation-like system for iron-sulfur cluster assembly under anaerobic conditions.

    • Author(s)
      Ali, V., Shigeta, Y., Tokumoto, U., Takahashi, Y., Nozaki, T.
    • Journal Title

      J. Biol. Chem. 279

      Pages: 16863-16874

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] (2004) Molecular and biochemical characterization of D-phosphoglycerate dehydrogenase from Entamoeba histolytica : a unique enteric protozoan parasite that possesses both phosphorylated and non-phosphorylated serine metabolic pathways.

    • Author(s)
      Ali, V., Hashimoto, T., Shigeta, Y., Nozaki, T.
    • Journal Title

      Eur. J. Biochem. 271

      Pages: 2670-2681

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] (2003) Molecular and structural characterization of NADPH-dependent D-glycerate dehydrogenase from the enteric parasitic protist Entamoeba histolytica.

    • Author(s)
      Ali, V., Shigeta, Y., Nozaki, T.
    • Journal Title

      Biochem. J. 375

      Pages: 729-736

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Patent(Industrial Property Rights)] 水溶性プロドラッグ2003

    • Inventor(s)
      木曽 良明
    • Industrial Property Rights Holder
      木曽 良明
    • Filing Date
      2003-07-11
    • Acquisition Date
      2005-02-03
    • Related Report
      2004 Annual Research Report

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Published: 2004-04-01   Modified: 2018-03-28  

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