权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

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：
10683288
负责人：
Diana M. Downs
金额：
$ 33.07万
依托单位：
UNIVERSITY OF GEORGIA
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

来源：
https://reporter.nih.gov/project-details/10683288
关键词：
Acceleration Active Sites Address Bacteria Bacterial Model Behavior Biochemical Biochemical Pathway Bioinformatics Biological Assay Biological Models Biology Campylobacter jejuni Catabolism Categories Cells Characteristics Chemicals Data Deaminase Disease Drug Design Enzymes Escherichia coli Excision Family Family member Funding Genes Genetic Genome Goals Grant Growth Human Knowledge Laboratories Life Metabolic Metabolic Control Metabolic Diseases Metabolic stress Metabolism Molecular Molecular Genetics Nature Organism Physiological Prevention Process Production Productivity Protein Family Proteins Pseudomonas aeruginosa Reaction Research Role Saccharomyces cerevisiae Salmonella enterica Stress Substrate Specificity System Uracil Water Work biological systems cell injury drug production environmental stressor enzyme activity fitness improved in vivo insight man member metabolic abnormality assessment metabolomics microbiome research model organism network dysfunction prevent response small molecule stressor synthetic biology transcriptomics

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

项目成果

期刊论文数量（39）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

From microbiology to cancer biology: the Rid protein family prevents cellular damage caused by endogenously generated reactive nitrogen species.

DOI：
10.1111/mmi.12945
发表时间：
2015-04
期刊：
Molecular microbiology
影响因子：
3.6
作者：
Downs DM;Ernst DC
通讯作者：
Ernst DC

Functional characterization of the HMP-P synthase of Legionella pneumophila (Lpg1565).

DOI：
10.1111/mmi.14622
发表时间：
2021-04
期刊：
Molecular microbiology
影响因子：
3.6
作者：
Paxhia MD;Swanson MS;Downs DM
通讯作者：
Downs DM

Loss of YggS (COG0325) impacts aspartate metabolism in Salmonella enterica.

DOI：
10.1111/mmi.14810
发表时间：
2021-10
期刊：
Molecular microbiology
影响因子：
3.6
作者：
Vu HN;Downs DM
通讯作者：
Downs DM

2-Aminoacrylate stress damages diverse PLP-dependent enzymes in vivo.

DOI：
10.1016/j.jbc.2022.101970
发表时间：
2022-06
期刊：
JOURNAL OF BIOLOGICAL CHEMISTRY
影响因子：
4.8
作者：
Shen, Wangchen;Borchert, Andrew J.;Downs, Diana M.
通讯作者：
Downs, Diana M.

RidA proteins prevent metabolic damage inflicted by PLP-dependent dehydratases in all domains of life.

DOI：
10.1128/mbio.00033-13
发表时间：
2013-02-05
期刊：
mBio
影响因子：
6.4
作者：
Lambrecht JA;Schmitz GE;Downs DM
通讯作者：
Downs DM

DOI：
{{ item.doi }}
发表时间：
{{ item.publish_year }}
期刊：
{{ item.journal_name }}
影响因子：
{{ item.factor }}
作者：
{{ item.authors }}
通讯作者：
{{ item.author }}

数据更新时间：{{ journalArticles.updateTime }}

作者：
{{ item.author }}

数据更新时间：{{ monograph.updateTime }}

作者：
{{ item.author }}

数据更新时间：{{ sciAawards.updateTime }}

作者：
{{ item.author }}

数据更新时间：{{ conferencePapers.updateTime }}

作者：
{{ item.author }}

数据更新时间：{{ patent.updateTime }}

Diana M. Downs其他文献

Thiamin biosynthesis in prokaryotes

DOI：
10.1007/s002030050713
发表时间：
1999-04-01
期刊：
ARCHIVES OF MICROBIOLOGY
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：
Microbiology Spectrum
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：
Scientific Reports
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