Administrative Supplement

行政补充

• 批准号: 10506086
• 负责人: Justin M Kollman
• 金额: $ 1.25万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-01 至 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10506086
• 关键词: Administrative Supplement; Biochemical; Biological; Biophysics; Cells; Coupled; Cryoelectron Microscopy; DNA; Disease; Environment; Enzymes; Filament; Glycolysis; In Vitro; Individual; Life; Medical; Metabolic; Metabolic Control; Metabolism; Molecular; Nucleotide Biosynthesis; Nutrient; Play; Process; RNA; Reaction; Regulation; Role; Speed; Structure; Work; enzyme activity; in vivo; insight; polymerization; response; self assembly; sugar

PROJECT SUMMARY Intermediate metabolism must be finely tuned, carefully balanced, and robustly adaptable to changes in environmental conditions. While the individual enzymes that drive most metabolic processes are well understood, only recently has the field come to appreciate the widespread role of metabolic enzyme self- assembly in metabolic organization and control. In particular, we now know that dozens of metabolic enzymes assemble into filamentous structures in vivo and in vitro, and that these filaments act as allosteric effectors to tune enzyme activity. This proposal focuses on self-assembled filaments of metabolic enzymes in glycolysis and nucleotide biosynthesis, processes that extract energy from sugar and generate fundamentally important macromolecular building blocks, respectively. We will use cryo-electron microscopy to determine the structural basis for assembly and regulation, coupled with biochemical, biophysical, and cell biological approaches in an integrative approach to understanding metabolic filament function. This work will provide insight into the specific roles polymerization plays in modulating enzyme function, and illuminate general principles of metabolic control by enzyme filaments.

项目摘要 中间的代谢必须经过精心调整，仔细平衡，并适应变化 环境条件。而驱动大多数代谢过程的单个酶很好 了解到，直到最近才开始欣赏代谢酶自我的广泛作用 代谢组织和控制中的组装。特别是，我们现在知道数十种代谢酶 在体内和体外聚集成丝状结构，这些丝充当变构效应子 调谐酶活性。该提案着重于糖酵解和 核苷酸生物合成，从糖中提取能量并产生重要重要的过程 大分子构建块。我们将使用冷冻电子显微镜确定结构 组装和调节的基础，再加上生化，生物物理和细胞生物学方法的基础 理解代谢丝功能的综合方法。这项工作将洞悉特定 角色聚合在调节酶功能中发挥作用，并阐明代谢控制的一般原理 通过酶丝。