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OXYGEN REGULATION OF NADH OXIDASE EXPRESSION IN STREPTOCOCCI

链球菌中 NADH 氧化酶表达的氧调节

基本信息

批准号：
09044200
负责人：
KAMIO Yoshiyuki
金额：
$ 2.88万
依托单位：
TOHOKU UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for international Scientific Research
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1998
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09044200/
关键词：
NADH oxidase nox gene AhpC ahpC gene Streptococcus mutans alkyl hydroperoxide reductase oxidative stress knockout mutants Streptococcus mutans NADH酸化

项目摘要

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.

我们以前曾发现，在耐氧变形链球菌中，氧暴露诱导了两种不同的NADH氧化酶，分别对应于H_2O_2形成氧化酶（Nox-1）和H_2O形成氧化酶（Nox-2）。此外，序列搜索表明Nox-1蛋白是鼠伤寒沙门氏菌AhpF的同源物，烷基氢过氧化物还原酶AhpR的黄素蛋白组分参与防御氧化应激，并表明nox-1基因上游的ahpC同源物与鼠伤寒沙门氏菌AhpC的存在，AhpR的非黄素蛋白组分。我们确定了由558 bp组成的编码186个氨基酸残基的AhpC的变形链球菌ahpC的完整序列，证实了这些蛋白质作为变形链球菌中AhpR系统的身份，证明了Nox-1和AhpC共同催化有机过氧化氢或H_2O_2还原为它们各自的醇和/或H_2O，以及Nox-2还原O_2的四电子还原，并提出变异链球菌的Nox-2含有半胱氨酸氧化还原中心; Nox-2蛋白的Cys 44在O2的四电子还原中发挥关键作用，证明Cys 44被Ser取代会改变O2还原化学计量，其中产物是H2 O2，而不是2 H2 O。此外，我们证实了Nox-1、Nox-2和AhpC的这些蛋白质是由氧诱导的，并且通过对Nox-1、Nox-2、AhpC的敲除突变体的分析，首次提出了Nox-2通过NAD的再生在有氧能量代谢中起重要作用的证据，而Nox-1的贡献可以忽略。我们还证明了Nox-1作为体内AhpR系统的一部分与AhpC组合的明确功能。