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OXYGEN REGULATION OF NADH OXIDASE EXPRESSION IN STREPTOCOCCI

Research Project

Project/Area Number 09044200
Research Category

Grant-in-Aid for international Scientific Research

Allocation TypeSingle-year Grants
SectionJoint Research
Research Field 応用微生物学・応用生物化学
Research InstitutionTOHOKU UNIVERSITY

Principal Investigator

KAMIO Yoshiyuki  TOHOKU UNIV/GRADUATE SCHOOL OF AGRI.PROFESSOR, 大学院・農学研究科, 教授 (00109175)

Co-Investigator(Kenkyū-buntansha) TOMITA Toshio  TOHOKU UNIV/GRADUATE SCHOOL OF AGRI.ASSIST.PROFESSOR, 大学院・農学研究科, 助教授 (00126129)
POOLE Leslie B.  WAKE-FOREST UNIV/SCHOOL OF MEDICINE,ASSOC.PROFESSOR, 医学部, 準教授
CLAIBORNE Al  WAKE-FOREST UNIV/SCHOOL OF MEDICINE,PROFESSOR, 医学部, 教授
Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥4,500,000 (Direct Cost: ¥4,500,000)
Fiscal Year 1998: ¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1997: ¥2,400,000 (Direct Cost: ¥2,400,000)
KeywordsNADH oxidase / nox gene / AhpC / ahpC gene / Streptococcus mutans / alkyl hydroperoxide reductase / oxidative stress / knockout mutants / Streptococcus mutans / NADH酸化
Research Abstract

We have previously revealed that two distinct NADH oxidases corresponding to H_2O_2-forming oxidase (Nox-1) and H_2O-forming oxidase (Nox-2) were induced in an oxygen tolerant Streptococcus mutans by exposure to oxygen. Furthermore, sequence searches indicated that the Nox-1 protein is homologue of Salmonella typhimurium AhpF, the flavoprotein component of alkyl hydroperoxide reductase AhpR involved in defense against oxidative stress, and suggested the presence of ahpC homologue upstream of nox-1 gene with S.typhimurium AhpC, the non-flavopretein component of AhpR.In this study, we determined the complete sequence of the S.mutans ahpC comprised of 558 bp encoding AhpC of 186 amino acid residues, confirmed the identity of these proteins as an AhpR system in S.mutans, demonstrated that together the Nox-1 and AhpC catalyzes the NADH-dependent reduction of organic hydroperoxides or H_2O_2 to their respective alcohols and/or H_2O, as well as the four-electron reduction of 0_2 by Nox-2, and proposed that Nox-2 from S.mutans contains a cysteinyl redox center ; the Cys44 of Nox-2 protein plays a key role in the overall four-electron reduction of O_2 to H_2O, by demonstrating that replacement of Cys44 with Ser provides for an altered O_2 reduction stoichiometry in which H_2O_2, not 2H_2O is the product. Furthermore, we confirmed that these proteins of Nox-1, Nox-2, and AhpC are induced by oxygen, and presented the first evidence that Nox-2 plays an important role in aerobic energy metabolism through the regeneration of NAD, but Nox-1 contributes negligibly, by analyses of knockout mutants of Nox-1, Nox-2, and/or AhpC.We also demonstrated a clear function for Nox-1 as part of an AhpR system in vivo in combination with AhpC.

Report

(3 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • Research Products

    (16 results)

All Other

All Publications (16 results)

  • [Publications] 樋口允子: "酸素障害防御の立役者-嫌気性菌のNADHオキシダーゼ" 化学と生物. 35(8). 547-555 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Mallett, T.C.: "Oxygen reactivity of an NADH oxidase C42S mutant : Evidence for a C(4a)-peroxyflavin intermediate and a rate-limiting conformational change." Biochemistry. 37(24). 8790-8802 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yamamoto, Y.: "Cloning, nucleotide sequence, and disruption of Streptococcus mutans glutathione reductase gene (gor)." Biosci.Biotechnol.Biochem.63(6). (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Poole, L.B.: "Flavins and Flavoproteins" University of Calgary Press, Calgary,4 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Higuchi, M.: "NADH oxidase in anaerobes for functions in defense against oxidative stress." Kagaku to Seibutsu. 35. 547-555 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Poole, L.B.: "NADH oxidase-1 and a second component encoded upstream of nox-1 comprise an alkyl hydroperoxide reductase system in Streptococcus mutans." Flavins and Flavoproteins University of Calgary Press, Calgary. 769-772 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Higuchi, M.: "Two types of NADH oxidases induced in Streptococcus mutans." Flavins and Flavoproteins University of Calgary Press, Calgary. 241-244 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Mallett, T.C.: "Oxygen reactivity of an NADH oxidase C42S mutant : Evidence for a C (4a) -peroxyflavin intermediate and a rate-limiting conformational change." Biochemistry. 37. 8790-8802 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yamamoto, Y.: "Cloning, nucleotide sequence, and disruption of Streptococcus mutans glutathione reductase gene (gor)." Biosci.Biotechnol.Biochem.63. (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Poole, L.B.: "Identification of the H202-forming NADH oxidase from Streptococcus mutans as part of an alkyl hydroperoxide reductase (AhpR) system ; comparison with AhpR from Salmonella typhimurium." J.Bacteriol.181. (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Higuchi, M.: "Functions for two types of NADH oxidases in energy metabolismm and oxidative stress." J.Bacteriol.181. (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 樋口允子: "酸素障害防御の立役者-嫌気性菌のNADHオキシダーゼ" 化学と生物. 35(8). 547-555 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] Mallett,T.C.: "Oxygen reactivity of an NADH oxidase C42S mutant:Evidence for a C(4a)-peroxyflavin intermediate ana a rate-lmiting conformational change." Biochemistry. 37(24). 8790-8802 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] yamamoto,Y.: "Cloning,nucleotide sequence,and disruption of Streptococcus mutans glutathione reductase gene(gor)." Biosci.Biotechnol.Biochem.63(6). (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Poole,L.B.: "Flavins and Flavoproteins" University of Calgary Press,Calgary,4 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] 樋口 允子: "酸素障害防御の立役者-嫌気性菌のNADHオキシダーゼ" 化学と生物. 35・8. 547-555 (1997)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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