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Development ofenzyme inlulkar far infectious diseace including malaria and clarification ofthe inlubitor activity

Research Project

Project/Area Number 18350086
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Chemistry related to living body
Research InstitutionOsaka University

Principal Investigator

INOUE Tsuyoshi  Osaka University, Graduate School of Engineering, Division ofApplied Chemistry, Associate Professor (20263204)

Co-Investigator(Kenkyū-buntansha) KAI Yasushi  Fukui University, of Technology, Department of Environmental and Biotechnological Frontier Engineering, Professor (40029236)
MATSUMURA Hiroyoshi  Osaka University, Graduate School of Engineering, Division ofApplied Chemistry, Assistant Professor (30324809)
Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥12,370,000 (Direct Cost: ¥10,300,000、Indirect Cost: ¥2,070,000)
Fiscal Year 2007: ¥8,970,000 (Direct Cost: ¥6,900,000、Indirect Cost: ¥2,070,000)
Fiscal Year 2006: ¥3,400,000 (Direct Cost: ¥3,400,000)
KeywordsPlasmodium falciparum / infectious desease / drug design / X-ray structure analysis
Research Abstract

Tropical diseases such as human malaria, leishmaniasis, Chagas disease, human African trypanosomiasis, dengue fever and schistosomiasis continue to cause significant morbidity and mortality. In this project, we performed X-ray crystallographic studies of important enzymes from parasite concerning three these infectious disease to construct the structural basis for the drug development by the in-silica method. The important enzymes are (1) two kinds of enzymes concerning the de novo synthesis of pyrimidine nucleotide from human malaria, (2) prostaglandin (PG) F synthases from parasites of Chagas' disease and Leishmania.
Recombinant enzymes of orotate phosphoribosyltransferase (pyr5) and Orotidine 5'-monophosphate decarboxylase (pyr6) were purified from E.coli and crystallized. As the result, the native and product UMP complex form of pyr6 were crystallized and carried out with the X-ray structural analyses. The 2.7 and 2.6 A resolutional structures of apo- and complex forms of pyr6 provided the details of the decarboxylation mechanism (J. Biochem., 2008). As for the PGF synthases from Trypanosoma cruzi and Leishmania mejor were also performed crystallization and the structure of PGF synthase from T. cruzi were determined at 1.7 A resolution (Acta Cryst. F, 2007). The complex structure of PGF sytnthase with indomethacin were also determined, providing the structural information for new inhibitor development.

Report

(3 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • Research Products

    (50 results)

All 2008 2007 2006

All Journal Article (26 results) (of which Peer Reviewed: 12 results) Presentation (18 results) Book (6 results)

  • [Journal Article] Structural basis for the decarboxylation of orotidine 5'-monophosphate(OMP)by Plasmodium falciparum OMP decarboxylase.2008

    • Author(s)
      K. Tokuoka, et. al.
    • Journal Title

      The Journal of Biochemistry 143巻

      Pages: 69-78

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Crystal structure of 5-methylthioribose 1-phosphate isomerase product complex from Bacillus subtilis: Implications for catalytic mechanism.2008

    • Author(s)
      H. Tamura, et. al.
    • Journal Title

      Protein Science 17巻

      Pages: 126-135

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Novel cation-pi interaction revealed by crystal structure of thermoalk alophilic lipase.2008

    • Author(s)
      H. Matsumura, et. al.
    • Journal Title

      PROTEINS: Structure, Function, and Bioinformatics 70巻

      Pages: 592-598

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Effect of Solution Flow by Rotary Shaker on Protein Crystallization.2008

    • Author(s)
      R. Murai, et. al.
    • Journal Title

      Journal of Crystal Growth 310巻

      Pages: 2168-2172

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Oxidation of archaeal peroxiredoxin involves a hypervalent sulfur intermediate.2008

    • Author(s)
      T. Nakamura, et. al.
    • Journal Title

      Proceedings of the National Academy of Sciences USA (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Structural basis for the decarboxylation of orotidine 5'-monophosphate (OMP) by Plasmodium Talon : Far= OMP decarboxylase.2008

    • Author(s)
      K., Tokuoka, et. al.
    • Journal Title

      The Journal of Biochemistry 143

      Pages: 69-78

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Crystal structure of 5-methylthioribose 1-phosphate isomerase product complex from Bacillus subtilis : Implications for catalytic mechanism.2008

    • Author(s)
      H., Tamura, et. al.
    • Journal Title

      Protein Science 17

      Pages: 126-135

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Novel cation-pi interaction revealed by crystal structure of thermoalkalophilic lipase2008

    • Author(s)
      H., Matsumura, et. al.
    • Journal Title

      PROTEINS : Structure, Function, and Bioinformatics 70

      Pages: 592-598

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Effect of Solution Flow by Rotary Shaker on Protein Crystallization2008

    • Author(s)
      R., Murai, et. al.
    • Journal Title

      Journal of Crystal Growth 310

      Pages: 2168-2172

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Oxidation of archaeal peroxiredoxin involves a hypervalent sulfur intermediate.2008

    • Author(s)
      T., Nakamura, et. al.
    • Journal Title

      Proceedings of the National Academy of Sciences USA (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Structural basis for the decarboxylation of orotidine 5'-monophosphate (OMP) by Plasmodium falciparum OMP decarboxylase.2008

    • Author(s)
      K. Tokuoka.
    • Journal Title

      The Journal of Biochemistry 143巻

      Pages: 69-78

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Crystal structure of 5-methylthioribose 1-phosphate isomerase productcomplex from Bacillus subtilis: Implications for catalytic mechanism.2008

    • Author(s)
      H. Tamura.
    • Journal Title

      Protein Science 17巻

      Pages: 126-135

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Novel cation-pi interaction revealed by crystal structure of thermoalkalophilic lipase.2008

    • Author(s)
      H. Matsumura.
    • Journal Title

      PROTEINS: Structure, Function, and Bioinformatics 70巻

      Pages: 592-598

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effect of Solution Flow by Rotary Shaker on Protein Crystallization.2008

    • Author(s)
      R. Murai.
    • Journal Title

      Journal of Crystal Growth (in press)

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Oxidation of archaeal peroxiredoxin involves a hypervalent sulfur intermediate.2008

    • Author(s)
      T. Nakamura.
    • Journal Title

      Proceedings of the National Academy of Sciences USA (in press)

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Preparation, crystallization and preliminary crystallographic analysis of old yellow enzyme from Trypanosoma cruzi.2007

    • Author(s)
      S. Sugiyama, et. al.
    • Journal Title

      Acta Crystallographica Section F 63巻

      Pages: 896-898

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Preparation, crystallization and preliminary crystallographic analysis of old yellow enzyme from Trypanosoma cruzi2007

    • Author(s)
      S., Sugiyama, et. al.
    • Journal Title

      Acta Crystallographica Section F 63

      Pages: 896-898

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Preparation, crystallization and preliminary crystallographic analysis of old yellow enzyme from Trypanosoma cruzi.2007

    • Author(s)
      S. Sugiyama.
    • Journal Title

      Acta Crystallographica Section F 63巻

      Pages: 896-898

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Structural and Functional Characterization of HQL-79, an Orally, Selective Inhibitor of Human Hematopoietic Prostaglandin D Synthase2006

    • Author(s)
      Kousuke Aritake, Yuji Kado, Tsuyoshi Inoue, Masashi Miyano, Yoshihiro Urade
    • Journal Title

      Journal of Biological Chemistry 281巻22号

      Pages: 15277-15286

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Crystal structure of intein homing endonuclease II encoded in the DNA polymerase gene from Hyperthermophilic Archaeon Thermococcus kodakaraensis strain KOD12006

    • Author(s)
      H.Matsumura, H.Takahashi, T.Inoue, T.Yamamoto, H.Hashimoto, M.Nishioka, S.Fujiwara, M.Takagi, T.Imanaka, Y.Kai
    • Journal Title

      Proteins : Structure Function, and Bioinformatics 63巻3号

      Pages: 711-715

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Application of Femtosecond Laser Ablation for Detaching Grown Protein Crystals from a Glass Capillary Tube2006

    • Author(s)
      M.Kashii, R.Fujisawa, H.Adachi, Y.Mori, T.Sasaki, Y.Koga, K.Takano, S.Kanaya, H.Matsumura, T.Inoue, S.Murakami, K.Sugamoto, H.Yoshikawa
    • Journal Title

      Journal of Bioscience and Bioengineering 102巻4号

      Pages: 372-374

    • NAID

      110004839458

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Effect of ultrasonic irradiation on protein crystallization2006

    • Author(s)
      K.Kakinouchi, H.Adachi, H.Matsumura, T.Inoue, S.Murakami, Y.Mori, Y.Koga, K.Takano, S.Kanaya
    • Journal Title

      Journal of Crystal Growth 292巻2号

      Pages: 437-440

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Cooling-rate screening system for determining protein crystal growth conditions2006

    • Author(s)
      R.Murai, S.Nakata, M.Kashii, H.Adachi, A.Niino, K.Takano, H.Matsumura, S.Murakami, T.Inoue, Y.Mori, T.Sasaki
    • Journal Title

      Journal of Crystal Growth 292巻2号

      Pages: 433-436

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Crystallization and preliminary crystallographic analysis of orotidine 5'-monophosphate decarboxylase from the human malaria parasite Plasmodium falciparum2006

    • Author(s)
      S.R.Krungkrai, K.Tokuoka, Y.Kusakari, T.Inoue, H.Adachi, H.Matsumura, K.Takano, S.Murakami, Y.Mori, Y.Kai, J.Krungkrai, T.Horii
    • Journal Title

      Acta Crystallographica Section F 62巻6号

      Pages: 542-545

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Purification, crystallization and preliminary X-ray diffraction of SecDF, a translocon-associated membrane protein, from Thermus thermophilus2006

    • Author(s)
      T.Tsukazaki, H.Mori, S.Fukai, T.Numata, A.Perederina, H.Adachi, H.Matsumura, K.Takano, S.Murakami, T.Inoue, Y.Mori, T.Sasaki, Dmitry, G.Vassylyev, O.Nureki, K.Ito
    • Journal Title

      Acta Crystallographica Section F 62巻4号

      Pages: 376-380

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Crystallization and preliminary X-ray analysis of the tRNA thiolation enzyme MnmA from Escherichia coli complexed with tRNA^<Glu>.2006

    • Author(s)
      T.Numata, Y.Ikeuchi, S.Fukai, H.Adachi, H.Matsumura, K.Takano, S.Murakami, T.Inoue, Y.Mori, T.Sasaki, T.Suzuki, O.Nureki
    • Journal Title

      Acta Crystallographica Section F 62巻4号

      Pages: 368-371

    • Related Report
      2006 Annual Research Report
  • [Presentation] The Crystal Structure of Orotidine 5' -monophosphate Decarboxylase from the Human Malaria Parasite Plasmodium falciparm.2008

    • Author(s)
      K. Tokuoka
    • Organizer
      The 1st International Global COE Symposium on Bio-Environmental Chemistry(GCOEBEC-1)
    • Place of Presentation
      Osaka(JAPAN)
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] The Crystal Structure of Orotidine 5'-monophosphate Decarboxylase from the Human Malaria Parasite Plasmodium falciparm2008

    • Author(s)
      K., Tokuoka
    • Organizer
      The 1st International Global COE Sympo-sium on Bio-Environmental Chemistry
    • Place of Presentation
      Osaka (JAPAN)
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Design of anti-allergic inhibitors for human hematopoietic prostagland in D synthase.2007

    • Author(s)
      T. Inoue
    • Organizer
      2nd International Symposium on Diffraction Structure Biology 2007(ISDSB2007)
    • Place of Presentation
      Tokyo(Japan)
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [Presentation] Preparation, crystallization and preliminary crystallographic analysis of old yellow enzyme from Trypanosoma cruzi.2007

    • Author(s)
      N. Okamoto
    • Organizer
      The 8th Conference of the Asian Crystallographic Association, AsCA' 07
    • Place of Presentation
      Taipei(TAIWAN)
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [Presentation] Crystallization and preliminary X-ray analysis of the Ceraroidase from Pseudomonas aeruginosa.2007

    • Author(s)
      H. Okano
    • Organizer
      The 8th Conference of the Asian Crystallographic Association, AsCA' 07
    • Place of Presentation
      Taipei(TAIWAN)
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Trypanosoma cruzi由来Old Yellow EnzymeのX線結晶構造解析2007

    • Author(s)
      岡本尚毅
    • Organizer
      日本結晶学会2007年度年会および総会
    • Place of Presentation
      東京
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 熱帯熱マラリア由来ピリミジン合成経路に関する酵素の結晶学的研究2007

    • Author(s)
      小西佐季
    • Organizer
      日本結晶学会2007年度年会および総会
    • Place of Presentation
      東京
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [Presentation] Crystal Structure analysis of Prostagland in F_<2α> synthase.2007

    • Author(s)
      徳岡啓司
    • Organizer
      第80回日本生化学会大会・第30回日本分子生物学会年会 合同大会 (BMB2007)
    • Place of Presentation
      横浜
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Design of anti-allergic inhibitors for human hematopoietic prostaglandin D synthase2007

    • Author(s)
      T., Inoue
    • Organizer
      2nd International Symposium on Diffraction Structure Biology 2007 (ISDSB2007)
    • Place of Presentation
      Tokyo (JAPAN)
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Preparation, crystallization and preliminary crystallographic analysis of old yellow enzyme from Bypanosoma cruzi2007

    • Author(s)
      N., Okamoto
    • Organizer
      The 8th Conference of the Asian Crystallographic Association, AsCA'07
    • Place of Presentation
      Taipei (TAIWAN)
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Crystallization and preliminary X-ray analysis of the Ceramidase from Pseudomonas aeruginosa2007

    • Author(s)
      H., Okano
    • Organizer
      The 8th Conference of the Asian Crystallographic Association, AsCA'07
    • Place of Presentation
      Taipei (TAIWAN)
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] X-ray analysis of Old Yellow Enzyme from Trypanosoma cruzi2007

    • Author(s)
      N., Okamoto
    • Organizer
      Annual Meeting 2007 and General Assembly CrSJ2007 in Tokyo
    • Place of Presentation
      Tokyo (JAPAN)
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Crystallographic studies on the enzymes in de novo pyrimidine biosynthesis of Human Malaria Parasite Plasmodium faciparum2007

    • Author(s)
      S., Konishi
    • Organizer
      Annual Meeting 2007 and General Assembly L'rSJ2007 in Tokyo
    • Place of Presentation
      Tokyo (JAPAN)
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Crystal Structure analysis of Prostaglandin F2. synthase.2007

    • Author(s)
      K., Tokuoka
    • Organizer
      Biochemistry and Molecular Biology 2007
    • Place of Presentation
      Yokohama (JAPAN)
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Crystallization and preliminary X-ray analysis of the Ceramidase from Pseudomonas aeruginosa.2007

    • Author(s)
      H. Okano
    • Organizer
      The 8th Conference of the Asian Crystallographic Association, AsCA' 07
    • Place of Presentation
      Taipei(TAIWAN)
    • Related Report
      2007 Annual Research Report
  • [Presentation] Trypanosoma cruzi由来01d Yellow EnzymeのX線結晶構造解析2007

    • Author(s)
      岡本尚毅
    • Organizer
      日本結晶学会2007年度年会および総会
    • Place of Presentation
      東京
    • Related Report
      2007 Annual Research Report
  • [Presentation] エイコサノイドネットワークの構造生物学と阻害剤開発の展望2007

    • Author(s)
      井上 豪
    • Organizer
      第80回日本生化学会大会・第30回日本分子生物学会年会 合同大会(BMB2007)
    • Place of Presentation
      横浜
    • Related Report
      2007 Annual Research Report
  • [Presentation] Crystal Structure analysis of Prostaglandin F_<2a> synthase.2007

    • Author(s)
      徳岡啓司
    • Organizer
      第80回日本生化学会大会・第30回日本分子生物学会年会 合同大会 (BMB2007)
    • Place of Presentation
      横浜
    • Related Report
      2007 Annual Research Report
  • [Book] 生物物理2007

    • Author(s)
      井上豪, 裏出良博
    • Total Pages
      8
    • Publisher
      日本生物物理学会
    • Related Report
      2006 Annual Research Report
  • [Book] ファルマシア2007

    • Author(s)
      井上豪, 福西快文, 坂田恒昭
    • Total Pages
      5
    • Publisher
      社団法人 日本薬学会
    • Related Report
      2006 Annual Research Report
  • [Book] 光学2007

    • Author(s)
      安達宏昭, 森勇介, 佐々木孝友, 高野和文, 井上豪, 松村浩由, 村上聡
    • Total Pages
      5
    • Publisher
      日本光学会
    • Related Report
      2006 Annual Research Report
  • [Book] 第5版 実験化学講座 5 化学実験のための基礎技術2006

    • Author(s)
      井上 豪, 松村浩由, 甲斐 泰
    • Total Pages
      15
    • Publisher
      丸善株式会社
    • Related Report
      2006 Annual Research Report
  • [Book] Functional and Structural Biology on the Lipo-network 20062006

    • Author(s)
      Yoshihiro Urade, Ikuko Mohri, Kosuke Aritake, Tsuyoshi Inoue, Masashi Miyano
    • Total Pages
      30
    • Publisher
      TRANSWORLD RESEARCH NETWORK
    • Related Report
      2006 Annual Research Report
  • [Book] 酵素工学ニュース2006

    • Author(s)
      安達宏昭, 森勇介, 佐々木孝友, 高野和文, 松村浩由, 井上豪, 村上聡
    • Total Pages
      5
    • Publisher
      酵素工学研究会
    • Related Report
      2006 Annual Research Report

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Published: 2006-04-01   Modified: 2016-04-21  

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