Diverse Transition-Metal and Free-Radical Chemistry Enabling 2'-Deoxyribonucleotide Production by Bacteria in Restrictive Environments

多种过渡金属和自由基化学使细菌在限制性环境中生产 2-脱氧核糖核苷酸

基本信息

  • 批准号:
    10165753
  • 负责人:
  • 金额:
    $ 37.74万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2019
  • 资助国家:
    美国
  • 起止时间:
    2019-06-01 至 2023-05-31
  • 项目状态:
    已结题

项目摘要

Project Summary/Abstract All organisms obtain the deoxynucleotide substrates for DNA synthesis and repair by the action of an enzyme known as ribonucleotide reductase (RNR). The several known types of RNRs, which have been divided into classes I, II, and III, differ in the transition-metal and free-radical chemistry that they use to initiate their common, challenging reduction/dehydroxylation reaction. Recent studies have shown that many bacteria that infect and cause disease in humans use class I RNRs that differ markedly from the human class I, subclass a enzyme. Some of these microbial RNRs (subclasses b and d) use manganese instead of iron in what is thought to be an adaptation to iron deprivation caused by the human immune response, and others use both metals (subclass c). We just discovered that a new type of RNR from the causative agent of strep throat and scarlet fever may have fully escaped the usual dependence on transition metals by using a previously unknown type of stable amino acid radical, thus founding subclass e. This project will reveal precisely how the members of three new subclasses of class I RNRs (including d and e) that were recently identified in pathogenic bacteria acquire their catalytic activity and initiate nucleotide reduction. The very different initiation chemistry used by the pathogens' enzymes offers opportunities for their selective inhibition by antibiotics. This project will provide the conceptual underpinnings for such drug discovery efforts and will shed light on the ways in which pathogenic microbes have adapted to cope with their hosts' hostile immune response.
项目总结/文摘

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

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JOSEPH M BOLLINGER其他文献

JOSEPH M BOLLINGER的其他文献

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{{ truncateString('JOSEPH M BOLLINGER', 18)}}的其他基金

Structures and Mechanisms of “Heme-oxygenase-like” Non-heme Di-iron Enzymes that Catalyze Complex N-oxygenation and Olefin-installing C–C-Fragmentation Reactions
催化复杂 N-氧化和烯烃安装 C-C 断裂反应的“类血红素加氧酶”非血红素双铁酶的结构和机制
  • 批准号:
    10647843
  • 财政年份:
    2020
  • 资助金额:
    $ 37.74万
  • 项目类别:
Structures and Mechanisms of “Heme-oxygenase-like” Non-heme Di-iron Enzymes that Catalyze Complex N-oxygenation and Olefin-installing C–C-Fragmentation Reactions
催化复杂 N-氧化和烯烃安装 C-C 断裂反应的“类血红素加氧酶”非血红素双铁酶的结构和机制
  • 批准号:
    10428624
  • 财政年份:
    2020
  • 资助金额:
    $ 37.74万
  • 项目类别:
Structures and Mechanisms of “Heme-oxygenase-like” Non-heme Di-iron Enzymes that Catalyze Complex N-oxygenation and Olefin-installing C–C-Fragmentation Reactions
催化复杂 N-氧化和烯烃安装 C-C 断裂反应的“类血红素加氧酶”非血红素双铁酶的结构和机制
  • 批准号:
    10035218
  • 财政年份:
    2020
  • 资助金额:
    $ 37.74万
  • 项目类别:
Structures and Mechanisms of “Heme-oxygenase-like” Non-heme Di-iron Enzymes that Catalyze Complex N-oxygenation and Olefin-installing C–C-Fragmentation Reactions
催化复杂 N-氧化和烯烃安装 C-C 断裂反应的“类血红素加氧酶”非血红素双铁酶的结构和机制
  • 批准号:
    10208910
  • 财政年份:
    2020
  • 资助金额:
    $ 37.74万
  • 项目类别:
Diverse Transition-Metal and Free-Radical Chemistry Enabling 2'-Deoxyribonucleotide Production by Bacteria in Restrictive Environments
多种过渡金属和自由基化学使细菌在限制性环境中生产 2-脱氧核糖核苷酸
  • 批准号:
    10417125
  • 财政年份:
    2019
  • 资助金额:
    $ 37.74万
  • 项目类别:
Mechanisms and Reprogramming of Iron/2-Oxoglutarate Desaturases and Oxacyclases
铁/2-氧戊二酸去饱和酶和氧杂环酶的机制和重编程
  • 批准号:
    9262989
  • 财政年份:
    2016
  • 资助金额:
    $ 37.74万
  • 项目类别:
Mechanisms and Reprogramming of Iron/2-Oxoglutarate Desaturases and Oxacyclases
铁/2-氧戊二酸去饱和酶和氧杂环酶的机制和重编程
  • 批准号:
    9084003
  • 财政年份:
    2016
  • 资助金额:
    $ 37.74万
  • 项目类别:
Mechanisms of oxacycle- and olefin-installing iron/2-(oxo)glutarate oxygenases
安装氧杂环和烯烃的铁/2-(氧代)戊二酸加氧酶的机制
  • 批准号:
    9139962
  • 财政年份:
    2015
  • 资助金额:
    $ 37.74万
  • 项目类别:
Mechanisms of oxacycle- and olefin-installing iron/2-(oxo)glutarate oxygenases
安装氧杂环和烯烃的铁/2-(氧代)戊二酸加氧酶的机制
  • 批准号:
    8965103
  • 财政年份:
    2015
  • 资助金额:
    $ 37.74万
  • 项目类别:
Mechanisms of oxacycle- and olefin-installing iron/2-(oxo)glutarate oxygenases
安装氧杂环和烯烃的铁/2-(氧代)戊二酸加氧酶的机制
  • 批准号:
    9309007
  • 财政年份:
    2015
  • 资助金额:
    $ 37.74万
  • 项目类别:
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