MEMBERS OF THE YJGF SUPERFAMILY NEUTRALIZE ENDOGENOUS METABOLIC STRESSORS

YJGF 超家族成员中和内源代谢应激源

基本信息

批准号：
8668074
负责人：
Diana M. Downs
金额：
$ 25.25万
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 2016-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8668074
关键词：
Affect Animal Model Bacteria Bacterial Proteins Biochemical Biochemical Pathway Bioinformatics Biological Assay Biology Biomedical Research Cells Cellular Assay Cellular Stress Chemicals Collaborations Data Deaminase Drug Design Environment Enzymes Family Family member Future Genetic Goals Growth Growth Factor Health In Vitro Learning Letters Life Literature Maps Metabolic Metabolic stress Metabolism Microbe Modeling Molecular Molecular Genetics Monitor Mutagenesis Names Nitrogen Organism Pathway interactions Phenotype Phylogenetic Analysis Process Production Protein Family Proteins Reaction Reactive Nitrogen Species Reporting Research Role Salmonella enterica Side Source Stress Substrate Specificity System Techniques Trees Work biological adaptation to stress biological systems chemical property coping environmental change genome sequencing in vitro Assay in vivo insight man member microbial mutant response small molecule stressor

项目摘要

DESCRIPTION (provided by applicant): A fundamental feature of a living system is an integrated network of biochemical pathways that can respond to stresses applied by the environment. Microbes, particularly those with a genetic system, provide a technically amenable system to characterize metabolic processes and stress responses. Metabolic strategies are conserved across biology, and insights obtained from microbial systems will contribute to our understanding of general metabolic paradigms. The long-term goal of my research is to contribute to the understanding of metabolic components and the processes they participate in. A rigorous understanding of metabolic processes is critical in efforts to predict the response of cells to environmental change, efforts to develop metabolic modeling strategies and efforts targeting metabolism for rational drug design and/or production of small molecules, to name a few. The goal of the work herein is to characterize a metabolic stress that results from reactive metabolites generated during growth, and to understand the family of proteins that neutralize this stress. This study focuses on a bacterial protein (YjgF) that is a member of highly conserved protein family that neutralizes reactive nitrogen species (e.g. enamines). In the current proposal, we will i) identify the stressors neutralized by the YjgF protein, ii) define the molecular consequences of not neutralizing this metabolic stress and iii) explore the relationship between sequence and functional divergence in the YjgF family. The goals of this proposal will be accomplished through the use of modern chemical, biochemical, biophysical, molecular, genetic and bioinformatic techniques. The work proposed here is motivated by our desire to understand the metabolic stress generated during growth by the production of reactive metabolites that can damage cellular components if they are not neutralized.

描述（由申请人提供）：生命系统的一个基本特征是一个集成的生化途径网络，可以响应环境施加的压力。微生物，特别是具有遗传系统的微生物，提供了技术上可行的系统来表征代谢过程和应激反应。代谢策略在整个生物学中都是保守的，从微生物系统获得的见解将有助于我们对一般代谢范式的理解。我研究的长期目标是促进对代谢成分及其参与过程的理解。对代谢过程的严格理解对于预测细胞对环境变化的反应、开发代谢建模策略至关重要以及针对合理药物设计和/或小分子生产的新陈代谢的努力，仅举几例。本文工作的目标是表征生长过程中产生的反应性代谢物引起的代谢应激，并了解中和这种应激的蛋白质家族。本研究重点关注细菌蛋白 (YjgF)，它是高度保守的蛋白质家族的成员，可中和活性氮（例如烯胺）。在当前的提案中，我们将 i) 识别 YjgF 蛋白中和的应激源，ii) 定义不中和这种代谢应激的分子后果，以及 iii) 探索 YjgF 家族中序列和功能分歧之间的关系。该提案的目标将通过使用现代化学、生物化学、生物物理、分子、遗传和生物信息技术来实现。这里提出的工作的动机是我们希望了解生长过程中由于反应性代谢物的产生而产生的代谢应激，如果不中和这些反应性代谢物，可能会损害细胞成分。