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STUDY ON RATIONAL DEVELOPMENT OF NOVEL ANTIBIOTICS TAGRETING DnaA DOMAIN IV

Research Project

Project/Area Number 13558090
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Molecular biology
Research InstitutionKyushu University

Principal Investigator

KATAYAMA Tsutomu  Kyushu University, Faculty of Pharmaceutical Sciences, Prof., 大学院・薬学研究院, 教授 (70264059)

Co-Investigator(Kenkyū-buntansha) KURUMIZAKA Hitoshi  Waseda Univ., Faculty of Engineering and Science, Assoc.Prof., 大学院・理工学部, 助教授 (80300870)
ASO Mariko  Kyushu University, Faculty of Pharmaceutical Sciences, Assis.Prof., 大学院・薬学研究院, 助手 (30201891)
UEDA Tadashi  Kyushu University, Faculty of Pharmaceutical Sciences, Prof., 大学院・薬学研究院, 教授 (90184928)
ENDO Atsushi  Dai-chi Pharmaceuticals Co., Researcher, 創薬第一研究所, 副主任研究員
Project Period (FY) 2001 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥11,200,000 (Direct Cost: ¥11,200,000)
Fiscal Year 2003: ¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 2002: ¥4,100,000 (Direct Cost: ¥4,100,000)
Fiscal Year 2001: ¥4,400,000 (Direct Cost: ¥4,400,000)
KeywordsDNA replication / Cell cycle / DnaA protein / E.coli / DNA polymerase / AAAt motif / ATP / Antibiotics / DNA結合 / NMR / X線結晶解析 / AAA+ファミリー / 染色体複製制御
Research Abstract

To establish rational process for developing novel antibiotics that targets DnaA protein, we analyzed structure-function relationship of the DNA-binding domain of DnaA, DnaA domain IV(DAD-IV). First, we overproduced and purified a truncated DnaA protein that contained only the DAD-IV. We found that DAD-IV sustains specific affinity for DNA and secondary structure by gel-retardation assay and CD analysis. Then we determined the secondary structure in solution of DAD-IV using NMR. Determined structure suggested that DAD-IV contained a three helices-bundled type helix-turn-helix motif. In addition, NMR analysis suggested that interaction sites of DAD-IV with DNA. Finally, we determined crystal structure of a complex of DAD-IV with DNA using X-ray diffraction analysis. Determined structure by this well coincided with the data obtained by NMR and by other biochemical and genetic analysis. Candidates of antibiotics were searched by the method of virtual screening, based on the structure of DAD-IV/DNA complex.

Report

(4 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • Research Products

    (51 results)

All Other

All Publications (51 results)

  • [Publications] Nishida, S., et al.: "A nucleotide switch in E.coli DnaA protein initiates the chromosomal replication : Evidence from a mutant DanA protein defective in regulatory ATP hydrolysis in vitro and in vivo"Journal of Biological Chemistry. 277. 14986-14995 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Obita, T.et al.: "Determination of the secondary structure in solution of the Escherichia coli DnaA DNA-binding domain"Biochemical and Biophysical Research Communications. 299. 42-48 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Onogi, T.et al.: "Replication-dependent recruitment of the β subunit of DNA polymerase III from cytsolic spaces to replication forks in Escherichia coli"Journal of Bacteriology. 184. 867-870 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Fujikawa, N.et al.: "Structural basis of replication origin recognition by the DnaA protein"Nucleic Acid Research. 31. 2077-2086 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Higuchi, K.et al.: "Fate of DNA replication fork encountering a single DNA I during oriC plasmid DNA replication in vitro"Genes to Cells. 8. 437-449 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Suetsugu, M., et al.: "Transcriptional control for initiation of chromosomal replication in Escherichia coli : fluctuation of the level of origin transcription ensures timely initiation"Genes to Cells. 8. 731-745 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yoshida, Y.et al.: "Identification of the region of Escherichia coli DnaA protein required for specific recognition of the DnaA box"Cell.Mol.Life Sci.. 60. 1998-2008 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Suetsugu, M.et al.: "Molecular mechanism of DNA replication-coupled inactivation of the initiator protein in Escherichia coli : Interaction of DnaA with the sliding clamp-loaded DNA and the sliding clamp-Hda complex"Genes to Cells. (In press). (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 片山 勉: "細菌染色体の複製制御機構"薬学研究の進歩. 19. 19-28 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Katayama, T.: "Feedback controls restrain the initiation of Escherichia coli chromosomal replication."Mol.Microbiol.. 41. 9-18 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kubota, T., et al.: "DnaA protein Lys-415 is close to the ATP-binding site : ATP-pyridoxal affinity labeling"Biochem.Biophys.Res.Commun.. 288. 1141-1148 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kato, J.et al.: "Hda, a novel DnaA-related protein, regulates the replication cycle in Escherichia coli."EMBO J.. 20. 4253-4262 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kawakami, H.et al.: "Arrest of cell division and nucleoid partition by genetic alterations in the sliding clamp of the replicase and DnaA protein"Mol.Genet.Genomics. 266. 167-179 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Katayama, T.et al.: "Multiple pathways regulating DnaA function in Escherichia coli : Distinct roles for DnaA titration by the datA locus and the regulatory inactivation of DnaA."Biochimie. 83. 13-17 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Suetsugu, M.et al.: "DNA replication-coupled inactivation of DnaA protein in vitro : a role for DnaA arginine-334 of the AAA^+ Box VIII motif in ATP hydrolysis."Mol.Microbiol.. 40. 376-386 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 片山 勉: "ゲノムの複製と分配(松影昭夫・正井久雄編)"シュプリンガーフェアラーク東京. 234 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 片山 勉: "今中忠行監修「ゲノミクスとプロテオミクスの新展開〜生物情報の解析と応用〜」"(株)エヌ・ティー・エス. 1158 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nishida, S., et al.: "A nucleotide switch in E.coli DnaA protein initiates the chromosomal replication : Evidence from a mutant DnaA protein defective in regulatory ATP hydrolysis in vitro and in vivo"Journal of Biological Chemistry. 277. 14986-14995 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Obita, T. et al.: "Determination of the secondary structure in solution of the Escherichia coli DnaA DNA-binding domain"Biochemical and Biophysical Research Communications. 299. 42-48 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Onogi, T. et al.: "Replication-dependent recruitment of the β subunit of DNA polymerase III from cytsolic spaces to replication forks in Escherichia coli"Journal of Bacteriology. 184. 867-870 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Fujikawa, N. et al.: "Structural basis of replication origin recognition by the DnaA protein"Nucleic Acid Research. 31. 2077-2086 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Higuchi, K. et al.: "Fate of DNA replication fork encountering a single DNA lesion during oriC plasmid DNA replication in vitro"Genes to Cells. 8. 437-449 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Su'etsugu, M., et al.: "Transcriptional control for initiation of chromosomal replication in Escherichia coli : fluctuation of the level of origin transcription ensures timely initiation"Genes to Cells. 8. 731-745 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yoshida, Y. et al.: "Identification of the region of Escherichia coli DnaA protein required for specific recognition of the DnaA box"Cell. Mol.Life Sci.. 60. 1998-2008 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Su'etsugu, M., et al.: "Molecular mechanism of DNA replication-coupled inactivation of the initiator protein in Escherichia coli : Interaction of DnaA with the sliding clamp-loaded DNA and the sliding clamp-Hda complex"Genes to Cells. (in press). (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Katayama, T.: "Feedback controls restrain the initiation of Escherichia coli chromosomal replication."Mol.Microbiol.. 41. 9-18 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kubota, T., et al.: "DnaA protein Lys-415 is close to the ATP-binding site : ATP-pyridoxal affinity labeling"Biochem.Biophys.Res.Commun.. 288. 1141-1148 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kato, J. et al.: "Hda, a novel DnaA-related protein, regulates the replication cycle in Escherichia coli."EMBO J.. 20. 4253-4262 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kawakami, H. et al.: "Arrest of cell division and nucleoid partition by genetic alterations in the sliding clamp of the replicase and DnaA protein"Mol.Genet.Genomics. 266. 167-179 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Katayama, T. et al.: "Multiple pathways regulating DnaA function in Escherichia coli : Distinct roles for DnaA titration by the datA locus and the regulatory inactivation of DnaA."Biochimie. 83. 13-17 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Su'etsugu, M., et al.: "DNA replication-coupled inactivation of DnaA protein in vitro : a role for DnaA arginine-334 of the AAA^+ Box VIII motif in ATP hydrolysis."Mol.Microbiol.. 40. 376-386 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Katayama, T.: "Regulatory mechanism for chromosome replication in bacteria"Advances in Pharmaceutical Sciences. 19. 19-28 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Katayama, T.: "Regulation of chromosome replication in prokayotes(Replication and Partition of the Genome(A.Matsukage and H.Masai(eds.))"Sringer-Verlag Tokyo. (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Katayama, T. et al.: "Replication system in the E.coli genome(Advances in Genomics and Proteomics(T.Imanaka(ed.))"N.T.S.. (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Fujikawa, N. et al.: "Structural basis of replication origin recognition by the DnaA protein"Nucleic Acid Res.. 31(8). 2077-2086 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yoshida, Y., et al.: "Identification of the region of Escherichia coli DnaA protein required for specific recognition of the DnaA box"Cell.Mol.Life Sci.. 60(9). 1998-2008 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Su'etsugu, M., et al.: "Transcriptional control for initiation of chromosomal replication in Escherichia coli : fluctuation of the level of origin transcription ensures timely initiation"Genes Cells. 8(9). 731-745 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Higuchi, K., et al.: "Fate of DNA replication fork encountering a single DNA lesion during oriC plasmid DNA replication in vitro"Genes Cells. 8(5). 437-449 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 片山 勉: "細菌染色体の複製制御機構"薬学研究の進歩. 19. 19-28 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 片山 勉, 他: "ゲノミクスとプロテオミクスの新展開〜生物情報の解析と応用〜"(株)エヌ・ティー・エス(印刷中). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Nishida, S., Fujimitsu, K., Sekimizu, K., Ohmura, T., Ueda, T., Katayama, T.: "A uncleotide switch in E. coil DnaA protein initiates the chromosomal replication : Evidence from a mutant DnaA protein defective in regulatory ATP hydrolysis and in vivo"Journal of Biological Chemistry. 277・17. 14986-14995 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Obita, T., Iwura, T., Su'etsugu, M., Yoshida, Y., Tanaka, Y., Katayama, T., Ueda, T., Imoto, T.: "Determination of the secondary structure in solution of the Escherichia DnaA DNA-binding domain"Biochemical and Biophysical Research Communications. 299・1. 42-48 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Onogi, T., Ohsumi, K., Katayama, T., Hiraga, S.: "Replication-dependent recruitment of the β subunit of DNA polymerase III from cytsolic spaces to replication forks in Escherichia coli"Journal of Becteriology. 184・3. 867-870 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Fujikawa, N., Kurumizaka, H., Nureki, O., Terada, T., Shirouzu, M., Katayama, T., Yokoyama, S.: "Structural basis of replication origin recognition by the DnaA protein"Nucleic Acid Research. (in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] 片山 勉(分担執筆): "ゲノムの複製とその制御(松影昭夫・正井久雄編)"シュプリンガーフェアラーク東京. 234 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Nishida, S., Fujimitsu, K., Sekimizu, K., Ohmura, T., Ueda, T., Katayama, T.: "A nucleotide switch in E.coli DnaA protein initiates the chromosomal replication : Evidence from a mutant DnaA protein defective in regulatory ATP hydrolysis in vitro and in vivo"Journal of Biological Chemistry. (印刷中). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Onogi, T., Ohsumi, K., Katayama, T., Hiraga, S.: "Replication-dependent recruitment of the β subunit of DNA polymerase III from cytsolic spaces to replication forks in Escherichia coli"Journal of Bacteriology. 183(4). 867-870 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kubota, T., Ito, Y., Sekimizu, K., Tagaya, M., Katayama, T.: "DnaA protein Lys-415is close to the ATP-binding site : ATP-pyridoxal affinity labeling"Biochem.Biophys.Res.Commun.. 288(5). 1141-1148 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kawakami, H., Iwura, T., Takata, M., Sekimizu, K., Hiraga, S., Katayama, T.: "Arrest of cell division and nucleoid partition by genetic alterations in the sliding clamp of the replicase and DnaA protein"Mol.Genet.Genomics. 266. 167-179 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kato, J., Katayama, T.: "Hda, a novel DnaA-related protein, regulates the replication cycle in Escherichia coli."EMBO Journal. 20(15). 4253-4262 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Su'etsugu, M., Kawakami, H., Kurokawa, K., Kubota, T., Takata, M., Katayama, T.: "DNA replication-coupled inactivation of DnaA protein in vitro : a role for DnaA arginine-334 of the AAA^+ Box VIII motif in ATP hydrolysis"Molecular Microbiology. 40(2). 376-386 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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