IRON REGULATORS OF THE FUR-TYPE FROM M TUBERCULOSIS AND A FERROOXIDANS

来自结核分枝杆菌和氧化亚铁的毛皮型铁调节剂

基本信息

  • 批准号:
    8362265
  • 负责人:
  • 金额:
    $ 0.06万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2011
  • 资助国家:
    美国
  • 起止时间:
    2011-03-01 至 2012-02-29
  • 项目状态:
    已结题

项目摘要

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Trace elements are essential for all living organisms. At the same time in cells the concentration of free metal ions is very low, because free redox-active metals can generate radicals, which can lead to cell damage. Others, such as Ca and Zn are participating in signaling processes. This implies the need for tight regulation. In mammals dysfunction of the regulation causes severe diseases. Bacteria would suffer from similar problems in case of too high or too low metal contents. Given the fact that mammalian and bacterial trace element regulation is based on different protein networks, the bacterial metal regulators have attracted considerable attention as potential drug targets. During the past years we have established our research on bacterial metal regulation. Pathogens, such as M. tuberculosis have to contend with iron sequestration in order to survive in the human body. Iron metabolism is regulated by controlling transcription of genes involved in iron uptake, transport and storage. In M. tuberculosis the ferric uptake regulator A (FurA) is activated by Fe2+ to bind specifically to its target DNA sequence thereby repressing the downstream genes. These genes include in homologous cases virulence factors and several proteins required by the bacterium for iron homeostasis. By x-ray absorption spectroscopy we will determine the metal binding sites of the protein. This allows distinguishing between two structurally and functionally distinct FurAMtb metal binding sites and provides a meticulous description plus a qualitative and quantitative characterization of them.
这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的, 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量, 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 微量元素对所有活着的有机体都是必不可少的。同时,细胞内游离金属离子的浓度很低,因为自由氧化还原活性金属会产生自由基,从而导致细胞损伤。其他的,如钙和锌,也参与了信号传递过程。这意味着有必要进行严格的监管。在哺乳动物中,调节功能的障碍会导致严重的疾病。如果金属含量过高或过低,细菌也会遇到类似的问题。鉴于哺乳动物和细菌的微量元素调控是基于不同的蛋白质网络,细菌金属调节剂作为潜在的药物靶点引起了人们的极大关注。在过去的几年里,我们已经建立了对细菌金属调控的研究。病原体,如结核分枝杆菌,为了在人体内生存,必须与铁的隔离作斗争。铁的代谢是通过控制与铁的吸收、运输和储存有关的基因的转录来调节的。在结核分枝杆菌中,铁摄取调节因子A(FURA)被Fe2+激活,与其靶DNA序列特异性结合,从而抑制下游基因。在同源病例中,这些基因包括毒力因子和细菌维持铁稳态所需的几种蛋白质。通过X射线吸收光谱,我们将确定蛋白质的金属结合部位。这使得能够区分两个结构和功能不同的FurAMtb金属结合位点,并提供了详细的描述以及对它们的定性和定量表征。

项目成果

期刊论文数量(0)
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科研奖励数量(0)
会议论文数量(0)
专利数量(0)

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WOLFRAM MEYER-KLAUCKE其他文献

WOLFRAM MEYER-KLAUCKE的其他文献

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{{ truncateString('WOLFRAM MEYER-KLAUCKE', 18)}}的其他基金

ON THE MECHANISM OF [NIFE]-HYDROGENASES
[NIFE]-加氢酶的作用机制研究
  • 批准号:
    8362264
  • 财政年份:
    2011
  • 资助金额:
    $ 0.06万
  • 项目类别:
HUMAN ETHE1: ACTIVITY AND CATALYTIC MECHANISM
人类 ETHE1:活性和催化机制
  • 批准号:
    8362263
  • 财政年份:
    2011
  • 资助金额:
    $ 0.06万
  • 项目类别:
BINDING OF CADMIUM AND ZINC BY A CD/ZN ATPASE INVOLVED IN METAL HYPERACCUMULATIO
涉及金属超积累的 CD/ZN ATP 酶对镉和锌的结合
  • 批准号:
    8362262
  • 财政年份:
    2011
  • 资助金额:
    $ 0.06万
  • 项目类别:
THE ACTIVE SITE OF [FE]- AND [NIFE]-HYDROGENASE
[FE]-和[NIFE]-氢化酶的活性位点
  • 批准号:
    8362261
  • 财政年份:
    2011
  • 资助金额:
    $ 0.06万
  • 项目类别:
HUMAN ETHE1: ACTIVITY AND CATALYTIC MECHANISM
人类 ETHE1:活性和催化机制
  • 批准号:
    8170252
  • 财政年份:
    2010
  • 资助金额:
    $ 0.06万
  • 项目类别:
METAL BINDING TO PLANT METALLOTHIONEINS
植物金属硫蛋白的金属结合
  • 批准号:
    8170253
  • 财政年份:
    2010
  • 资助金额:
    $ 0.06万
  • 项目类别:
ON THE MECHANISM OF [NIFE]-HYDROGENASES
[NIFE]-加氢酶的作用机制研究
  • 批准号:
    8170254
  • 财政年份:
    2010
  • 资助金额:
    $ 0.06万
  • 项目类别:
THE ACTIVE SITE OF [FE]- AND [NIFE]-HYDROGENASE
[FE]-和[NIFE]-氢化酶的活性位点
  • 批准号:
    8170250
  • 财政年份:
    2010
  • 资助金额:
    $ 0.06万
  • 项目类别:
BINDING OF CADMIUM AND ZINC BY A CD/ZN ATPASE INVOLVED IN METAL HYPERACCUMULATIO
涉及金属超积累的 CD/ZN ATP 酶对镉和锌的结合
  • 批准号:
    8170251
  • 财政年份:
    2010
  • 资助金额:
    $ 0.06万
  • 项目类别:
IRON REGULATORS OF THE FUR-TYPE FROM M TUBERCULOSIS AND A FERROOXIDANS
来自结核分枝杆菌和氧化亚铁的毛皮型铁调节剂
  • 批准号:
    8170255
  • 财政年份:
    2010
  • 资助金额:
    $ 0.06万
  • 项目类别:

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