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Dynamic structure of intermedilysin : Analysis of membrane binding region

Research Project

Project/Area Number 15590098
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Drug development chemistry
Research InstitutionNagoya University

Principal Investigator

OHKURA Kazuto  Nagoya University, Grad.Sch.Bioagr.Sci., Assistant Prof., 大学院・生命農学研究科, 助手 (00242850)

Co-Investigator(Kenkyū-buntansha) HORI Hitoshi  Univ.Tokushima, Dep.Biol.Sci.Tech., Fac.Eng., Prof., 工学部, 教授 (90119008)
TSUGE Hideaki  Tokushima Bunri Univ., Inst.Health Sci., Prof., 健康科学研究所, 教授 (40299342)
Project Period (FY) 2003 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2004: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2003: ¥1,900,000 (Direct Cost: ¥1,900,000)
Keywordsinfection / cytolysin
Research Abstract

Background : Intermedilysin (ILY) is a human-specific cytolysin secreted from Streptococcus intermedius. In this study, we analyzed the dynamic structure of ILY, Streptolysin O (SLO) and their 12mer substituted mutants during 500ps. Several parameters, such as dipole moment and electrostatic potential, were determined to discuss the molecular mechanism of membrane binding.
Material and Methods : Molecular models of ILY, SLO and their mutants were constructed using InsightII-Discover with the Homology module. Their molecular dynamics were simulated with the Discover3 module, and z-matrix data of the membrane-binding 12mer region were extracted to calculate the MO parameters (i.e. dipole moment, solvation free energy (dGW)).
Results : Cytolysins vibrated like a bow, and the dipole moment direction of ILY 12mer region was different from that of SLO. Certain ILY mutants indicated the SLO-like dipole properties, which had an SLO-type 11mer cysteine motif amino acid sequence. The ILY 11mer region was more hydrophobic than that of SLO, and seemed to easy interact with the cell membrane without cholesterol. The electrostatic potential field distribution of ILY differed from that of SLO, especially in the 11mer region.
Conclusion : In the 11mer region, the dipole moment directions of these cytolysins were constant during molecular movement, and ready to interact with membrane components (i.e. cholesterol, phospholipid) in each style.

Report

(4 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • 2003 Annual Research Report
  • Research Products

    (21 results)

All 2005 2004 Other

All Journal Article (17 results) Publications (4 results)

  • [Journal Article] Intermedilysin is Essential for the Invasion of Hepatoma HepG2 cells by Streptococcus intermedius2005

    • Author(s)
      Akiko Sukeno
    • Journal Title

      Microbiology and Immunology 49・7

      Pages: 681-694

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Bridge-linked Bis-quaternary Ammonium Antimicrobial Agents : Relationship between Cytotoxicity and Antibacterial Activity of 5,5'-〔2,2'-(tetramethylenedicarbonyldioxy)diethyl〕bis(3-alkyl-4-methylthiazonium iodide)s2005

    • Author(s)
      Kazuto Ohkura
    • Journal Title

      Bioorganic and medicinal Chemistry 13・7

      Pages: 2579-2587

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Molecular Basis of Group A Streptococcal Pyrogenic Exotoxin B2005

    • Author(s)
      Hideaki Nagamune
    • Journal Title

      Journal of Infection and Chemotheapy 11・1

      Pages: 1-8

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Intermedilysin is Essential for the Invasion of Hepatoma HepG2 cells by Streptococcus intermedius2005

    • Author(s)
      Akiko Sukeno, Hideaki Nagamune, Robert A.Whiley, Syed I.Jafar, Joseph Aduse-Opoku, Kazuto Ohkura, Takuya Maeda, Katsuhiko Hirota, Yoichiro Miyake, Hiroki Kourai
    • Journal Title

      Microbiology and Immunology Vol.49-No.7

      Pages: 681-694

    • NAID

      10016568016

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Bridge-linked Bis-quaternary Ammonium Antimicrobial Agents : Relationship between Cytotoxicity and Antibacterial Activity of 5,5'-[2,2'-(tetramethylenedicarbonyldioxy)diethyl]bis(3-alkyl-4-methylthiazonium iodide)s2005

    • Author(s)
      Kazuto Ohkura, Akiko Sukeno, Hideaki Nagamune, Hiroki Kourai
    • Journal Title

      Bioorganic and Medicinal Chemistry Vol.13-No.7

      Pages: 2579-2587

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Molecular Basis of Group A Streptococcal Pyrogenic Exotoxin B2005

    • Author(s)
      Hideaki Nagamune, Kazuto Ohkura, Hisashi Ohkuni
    • Journal Title

      Journal of Infection and Chemotherapy Vol.11-No.1

      Pages: 1-8

    • NAID

      10014469726

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Bridge-linked Bis-quaternary Ammonium Antimicrobial Agents : Relationship between Cytotoxicity and Antibacterial Activity of 5,5'-[2,2'-(tetramethylenedicarbonyldioxy) diethyl]bis(3-alkyl-4-methylthiazonium iodide)s2005

    • Author(s)
      Kazuto Ohkura
    • Journal Title

      Bioorganic and Medicinal Chemistry 13・7

      Pages: 2579-2587

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Molecular Basis of Group A Streptococcal Pyrogenic Exotoxin B2005

    • Author(s)
      Hideaki Nagamune
    • Journal Title

      Journal of Infection and Chemotherapy 11・1

      Pages: 1-8

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Molecular Basis of Group A Streptococcal Pyrogenic Exotoxin B.2005

    • Author(s)
      Nagamune, H.
    • Journal Title

      J.Infect.Chemother. (in press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Bridge-linked Bis-quaternary Ammonium Antimicrobial Agents : Relationship between Cytotoxicity and Antibacterial Activity of 5,5'-[2,2'-(tetramethylenedicarbonyldioxy) diethyl]bis(3-alkyl-4-methylthiazonium iodide)s.2005

    • Author(s)
      Ohkura, K.
    • Journal Title

      Bioorg.Med.Chem. (in press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] A Cell Membrane Modification Technique using Domain 4 of Intermedilysin for Immunotherapy against Cancer2004

    • Author(s)
      Hideaki Nagamune
    • Journal Title

      Anticancer Research 24・5

      Pages: 3367-3372

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Structural Analysis of Human Specific Cytolysin Intermedilysin aiming Application to Cancer Immunotherapy2004

    • Author(s)
      Kazuto Ohkura
    • Journal Title

      Anticancer Research 24・5

      Pages: 3343-3354

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] The Human-specific Action of Intermedilysin, a Homologue of Streptolysin O,is Dictated by Domain 4 of the Protein2004

    • Author(s)
      Hideaki Nagamune
    • Journal Title

      Microbiology and Immunology 48・9

      Pages: 677-692

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] A Cell Membrane Modification Technique using Domain 4 of Intermedilysin for Immunotherapy against Cancer2004

    • Author(s)
      Hideaki Nagamune, Kazuto Ohkura, Kazunori Umezu, Hidekatsu Shoji, Hiroki Kourai
    • Journal Title

      Anticancer Research Vol.24-No.5C

      Pages: 3367-3372

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Structural Analysis of Human Specific Cytolysin Intermedilysin aiming Application to Cancer Immunotherapy2004

    • Author(s)
      Kazuto Ohkura, Hideaki Nagamune, Hiroki Kourai
    • Journal Title

      Anticancer Research Vol.24-No.5C

      Pages: 3343-3354

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] The Human-specific Action of Intermedilysin, a Homologue of Streptolysin O, is Dictated by Domain 4 of the Protein2004

    • Author(s)
      Hideaki Nagamune, Kazuto Ohkura, Akiko Sukeno, Graeme Cowan, Timothy J.Mitchell, Wataru Ito, Ooki Ohnishi, Kanako Hattori, Miki Yamato, Katsuhiko Hirota, Yoichiro Miyake, Takuya Maeda, Hiroki Kourai
    • Journal Title

      Microbiology and Immunology Vol.48-No.9

      Pages: 677-692

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] The Human-specific Action of Intermedilysin, a Homologue of Streptolysin O, is Dictated by Domain 4 of the Protein.2004

    • Author(s)
      Nagamune, H.
    • Journal Title

      Microbiol.Immunol. 48

      Pages: 677-692

    • Related Report
      2004 Annual Research Report
  • [Publications] Ohkura, K.: "Structural Analysis of Human Specific Cytolysin Intermedilysin aiming Application to Cancer Immunotherapy"Anticancer Research. (in press).

    • Related Report
      2003 Annual Research Report
  • [Publications] Nagamune, H.: "A Cell Modification Technique using Domain4 of Intermedilysin for Immunotherapy against Cancer"Anticancer Research. (in press).

    • Related Report
      2003 Annual Research Report
  • [Publications] Hori, H.: "Design of hypoxia-targeting protein tyrosine kinase inhibitor using an innovative pharmacophore 2-methylene-4-cyclopentene-1,3-dione"Biochimica et Biophysica Acta. 1697. 29-38 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ohkura, K.: "Analysis of Structural Features of Bis-Quaternary Ammonium Antimicrobial Agents 4,4'-α,ω-Polymethylenedithio)bis(1-alkylpyridinium lodide)s Using computational Simulation"Bioorganic & Medicinal Chemistry. 11. 5035-5043 (2003)

    • Related Report
      2003 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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