Sirtuins and Metabolic Pathway Integration

Sirtuins 和代谢途径整合

基本信息

批准号：
9212813
负责人：
JORGE C ESCALANTE
金额：
$ 34.22万
依托单位：
UNIVERSITY OF GEORGIA
依托单位国家：
美国
项目类别：
财政年份：
2001
资助国家：
美国
起止时间：
2001-01-01 至 2019-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9212813
关键词：
Acetate-CoA Ligase Acetates Acetyl Coenzyme A Acetylation Acetyltransferase Acylation Acyltransferase Address Area Bacteria Biochemical Biochemical Pathway Biological Biotechnology Carbon Catabolism Catalytic Domain Cell physiology Cells Chemicals Coenzyme A Collaborations Complex Conflict (Psychology)Controlled Study Crystallography DNA-Binding Proteins Dimensions Enzymes Epigenetic Process Evolution Face Funding Gene Expression Genes Genetic Goals Grant Growth Health Homeostasis Human In Vitro Inositol Knowledge Laboratory Study Learning Lysine Metabolic Pathway Metabolism Microbe Modification Molecular Nature Operon Phenotype Phosphorylation Physiology Post-Translational Protein Processing Principal Investigator Prokaryotic Cells Protein Analysis Proteins Reporting Research Resistance Role Salmonella Salmonella enterica Sirtuins Specificity Stimulus Streptomyces Streptomyces lividans System Time Work acetyl phosphate cell motility improved in vivo insight interest mutant photosynthetic bacteria pressure protein function protein structure public health relevance response

项目摘要

DESCRIPTION (provided by applicant): In nature, microbes face a spectacular array of stimuli that challenge their survival. Collectively, these stimuli exert a strong selective pressure for th evolution of sophisticated, rapid-response mechanisms that can efficiently maintain homeostasis through the modulation of functions of diverse biomolecules. Not surprisingly, biologists are interested in understanding how these mechanisms work, how they are regulated, and how they are integrated into the cellular regulatory circuits. The PI's laboratory studies the control of protein function by chemical modifications, with an emphasis on reversible lysine acylation (RLA). Ten years ago, the PI's group reported the first evidence of RLA in prokaryotes, a discovery that elicited a great deal of interest. In a short period of time, RLA has emerged as a posttranslational modification that rivals phosphorylation in terms of its breadth and impact on the dynamics of the complex metabolic network of the cell. In recent years, the PI's group has reported the impact of RLA on central cellular processes such as cell motility, gene expression, carbon metabolism, energy and coenzyme A homeostasis. The PI's laboratory studies the control of protein function by RLA. The long-term goal of the work supported by grant R01-GM062203 is to understand the contributions of RLA to cell function. The PI's group will continue to apply comprehensive genetic, molecular biological, biochemical, structural, and system-wide approaches to answer fundamental questions regarding the mechanism of RLA function. Work proposed herein seeks to: i) learn the molecular details of how acetyltransferases recognize their protein substrates; ii) gain insights into the mechanism of acetyltransferase function; iii) gain a better understanding of how proteins evolve to escape RLA control; and iv) define the regulatory circuit that integrates RLA into the complex metabolic network of the cell.

描述（由申请人提供）：在本质上，微生物面临着挑战其生存的壮观刺激。总的来说，这些刺激为复杂的快速响应机制的演变施加了强大的选择压力，可以通过调节各种生物分子的功能来有效地维持稳态。毫不奇怪，生物学家有兴趣了解这些机制的工作原理，如何调节以及如何整合到细胞调节电路中。 PI的实验室研究通过化学修饰对蛋白质功能的控制，重点是可逆的赖氨酸酰化（RLA）。十年前，PI小组报道了原核生物中RLA的第一个证据，这一发现引起了极大的兴趣。在短时间内，RLA已成为翻译后的修饰，其广度及其对细胞复杂代谢网络的动力学的影响匹配磷酸化。近年来，PI组报告了RLA对中央细胞过程的影响，例如细胞运动，基因表达，碳代谢，能量和辅酶A稳态。 PI的实验室研究RLA对蛋白质功能的控制。赠款R01-GM062203支持的工作的长期目标是了解RLA对细胞功能的贡献。 PI的组将继续采用全面的遗传，分子生物学，生化，结构和全系统的方法来回答有关RLA功能机制的基本问题。本文提出的工作试图：i）学习乙酰基转移酶如何识别其蛋白质底物的分子细节； ii）洞悉乙酰转移酶功能的机理； iii）更好地了解蛋白质如何发展为逃避RLA控制； iv）定义将RLA集成到细胞复杂代谢网络中的调节电路。