Rid family members neutralize endogenous metabolic stressors

Rid 家族成员中和内源性代谢应激源

基本信息

  • 批准号:
    10260571
  • 负责人:
  • 金额:
    $ 34.04万
  • 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:
    2011-09-01 至 2024-08-31
  • 项目状态:
    已结题

项目摘要

SUMMARY A fundamental feature of a living system is its integrated network of biochemical pathways that respond to endogenous and environmental stresses. In humans, there is a strong connection between metabolic network dysfunction and disease. Metabolic strategies are conserved across biology, and insights obtained from model organisms provide the means to advance our understanding of general metabolic paradigms, which can often be extrapolated to higher organisms including humans. The long-term goal of the PI's research is to understand the robustness and redundancy of the metabolic network, and to define metabolic components and the processes they participate in. Knowledge of metabolic processes and a mechanistic understanding of the function of unknown proteins is critical to efforts aimed at treating metabolic diseases, and to efforts targeting metabolism for rational drug design, synthetic biology, microbiome research, etc. The goal of the work proposed herein is to advance our understanding of the metabolic stress caused by the 2-aminoacrylate, an obligate intermediate in central metabolic reactions, and the protein that controls it, RidA. Further, this study focuses on the highly conserved Rid protein family, of which RidA is the founding member. In the current proposal we will: i) describe additional, distinct mechanisms that have evolved to deal with similar stress; ii) explore the breadth of 2-aminoacrylate stress and how different organisms handle it, and iii) define the molecular mechanism and cellular role of additional Rid proteins. The goals of this proposal will be accomplished through a combination of chemical, biochemical, molecular genetic, bioinformatics and global approaches. The work here is motivated by our desire to understand the metabolic stress generated by the production of reactive metabolites during growth, how it can damage cellular components if it is not neutralized, and discovering the role of additional members of the broadly conserved protein family that includes RidA.
总结 生命系统的一个基本特征是其生物化学途径的集成网络, 内源性和环境压力。在人类中,代谢网络之间存在密切联系 功能障碍和疾病。代谢策略在生物学中是保守的,从模型中获得的见解 生物体提供的手段,以促进我们的一般代谢模式的理解,这往往可以 可以外推到包括人类在内的高等生物。PI研究的长期目标是 了解代谢网络的鲁棒性和冗余性,并定义代谢组件, 他们参与的过程。代谢过程的知识和机械的理解, 未知蛋白质的功能对于旨在治疗代谢性疾病的努力以及靶向 用于合理药物设计的代谢、合成生物学、微生物组研究等。 本文所提出的工作的目标是促进我们对代谢应激的理解, 2-氨基丙烯酸酯,中枢代谢反应中的专性中间体,以及控制它的蛋白质RidA。 此外,本研究的重点是高度保守的Rid蛋白家族,其中RidA是创始成员。 在当前的提案中,我们将:i)描述已经发展起来的额外的、不同的机制来处理 类似的压力; ii)探索2-氨基丙烯酸酯压力的广度以及不同生物体如何处理它,以及iii) 定义额外的Rid蛋白的分子机制和细胞作用。本提案的目标是 通过化学,生物化学,分子遗传学,生物信息学和全球 接近。这项工作的动机是我们希望了解代谢应激产生的 在生长过程中产生反应性代谢物,如果不中和,它如何损害细胞成分, 并发现包括RidA在内的广泛保守的蛋白质家族的其他成员的作用。

项目成果

期刊论文数量(0)
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Diana M. Downs其他文献

Thiamin biosynthesis in prokaryotes
  • DOI:
    10.1007/s002030050713
  • 发表时间:
    1999-04-01
  • 期刊:
  • 影响因子:
    2.600
  • 作者:
    T. P. Begley;Diana M. Downs;Steven E. Ealick;Fred W. McLafferty;Adolphus P. G. M. Van Loon;Sean Taylor;Nino Campobasso;Hsiu-Ju Chiu;Cynthia Kinsland;Jason J. Reddick;Jun Xi
  • 通讯作者:
    Jun Xi
Purine limitation prevents the exogenous pyridoxal 5′-phosphate accumulation of emSalmonella enterica yggS/em mutants
嘌呤限制阻止了肠沙门氏菌 yggS 外源性吡哆醛 5′-磷酸的积累
  • DOI:
    10.1128/spectrum.02075-24
  • 发表时间:
    2024-10-30
  • 期刊:
  • 影响因子:
    3.800
  • 作者:
    Kailey S. Ezekiel;Diana M. Downs
  • 通讯作者:
    Diana M. Downs
Biochemical and structural characterization of a reactive intermediate deaminase A homolog from Streptococcus sanguinis
来自血链球菌的一种反应性中间脱氨酶 A 同源物的生化和结构表征
  • DOI:
    10.1038/s41598-025-05264-x
  • 发表时间:
    2025-07-01
  • 期刊:
  • 影响因子:
    3.900
  • 作者:
    Alexa B. Benedict;Adreana I. Aquino;Brandi A. Buckner;Swarmistha Devi Aribam;Chhandosee Ganguly;Leonard M. Thomas;Philip Bourne;Rakhi Rajan;Diana M. Downs;Vijayakumar Somalinga
  • 通讯作者:
    Vijayakumar Somalinga

Diana M. Downs的其他文献

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{{ truncateString('Diana M. Downs', 18)}}的其他基金

The RidA examine deaminase links metabolism with virulence in Campylobacter jejuni
RidA 研究脱氨酶将空肠弯曲杆菌代谢与毒力联系起来
  • 批准号:
    10204983
  • 财政年份:
    2020
  • 资助金额:
    $ 34.04万
  • 项目类别:
The RidA examine deaminase links metabolism with virulence in Campylobacter jejuni
RidA 研究脱氨酶将空肠弯曲杆菌代谢与毒力联系起来
  • 批准号:
    10039719
  • 财政年份:
    2020
  • 资助金额:
    $ 34.04万
  • 项目类别:
Rid family members neutralize endogenous metabolic stressors
Rid 家族成员中和内源性代谢应激源
  • 批准号:
    10469647
  • 财政年份:
    2011
  • 资助金额:
    $ 34.04万
  • 项目类别:
Rid family members neutralize endogenous metabolic stressors
Rid 家族成员中和内源性代谢应激源
  • 批准号:
    10673400
  • 财政年份:
    2011
  • 资助金额:
    $ 34.04万
  • 项目类别:
Rid family members neutralize endogenous metabolic stressors
Rid 家族成员中和内源性代谢应激源
  • 批准号:
    10683288
  • 财政年份:
    2011
  • 资助金额:
    $ 34.04万
  • 项目类别:
Members of the YjgF superfamily neutralize endogenous metabolic stressors.
YjgF 超家族的成员可以中和内源性代谢应激源。
  • 批准号:
    8186208
  • 财政年份:
    2011
  • 资助金额:
    $ 34.04万
  • 项目类别:
Rid family members neutralize endogenous metabolic stressors
Rid 家族成员中和内源性代谢应激源
  • 批准号:
    9323487
  • 财政年份:
    2011
  • 资助金额:
    $ 34.04万
  • 项目类别:
Diversity Enhancement Supplement
多样性增强补充
  • 批准号:
    10328806
  • 财政年份:
    2011
  • 资助金额:
    $ 34.04万
  • 项目类别:
Rid family members neutralize endogenous metabolic stressors
Rid 家族成员中和内源性代谢应激源
  • 批准号:
    10467136
  • 财政年份:
    2011
  • 资助金额:
    $ 34.04万
  • 项目类别:
MEMBERS OF THE YJGF SUPERFAMILY NEUTRALIZE ENDOGENOUS METABOLIC STRESSORS
YJGF 超家族成员中和内源代谢应激源
  • 批准号:
    8668074
  • 财政年份:
    2011
  • 资助金额:
    $ 34.04万
  • 项目类别:

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