Mapping the structural basis for mechanistic diversity in metalloenzyme superfamilies

绘制金属酶超家族机械多样性的结构基础

• 批准号: 10407038
• 负责人: Amie K Boal
• 金额: $ 42.09万
• 依托单位: PENNSYLVANIA STATE UNIVERSITY, THE
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-08-01 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10407038
• 关键词: Biological; Chemicals; DNA biosynthesis; Drug Targeting; Engineering; Enzyme Inhibition; Enzymes; Family; Metals; Modification; Outcome; Process; Reaction; Route; Structure; System; Trace Elements; Transition Elements; Work; biological systems; chemical bond; chemical reaction; cofactor; comparative; drug synthesis; metalloenzyme; novel; pathogen; pathogenic bacteria; tool

Project Summary Enzymes that employ transition metals can initiate chemically challenging modifications of inert chemical bonds. These systems serve as both important drug targets and useful biocatalysts. In certain transition-metal driven essential biological transformations, such as DNA biosynthesis, divergent trace elements can be used for reaction initiation. Discovery of novel metal cofactors used for these processes, and their mechanisms of assembly and deployment, will enable novel routes of enzyme inhibition in bacterial pathogens. In a second project, structures and reaction mechanisms in three different metalloenzyme superfamilies relevant to biocatalysis will be elucidated. These systems use a common cofactor to catalyze divergent reaction outcomes, controlled by structural features of each enzyme. A comparative approach provides detailed and testable hypotheses about the means by which distinct chemical reactions are accomplished, as well as discovery of entirely new families of enzymes and new ways to control their activities. The objective of this work is to enable exploitation of the catalytic power inherent in these systems for more efficient and environmentally friendly synthesis of drugs, chemicals, technological tools, and new chemical processes.

项目摘要 采用过渡金属的酶可以引发化学挑战性的修饰 惰性化学键。这些系统既是重要的药物靶标，又是有用的 生物催化剂。在某些过渡金属驱动的基本生物学转化中， 作为DNA生物合成，可以使用不同的微量元素进行反应起始。 发现用于这些过程的新型金属辅因子及其机制 组装和部署将实现细菌中新型酶抑制的途径 病原体。在第二个项目中，三种不同的结构和反应机制 将阐明与生物催化有关的金属酶超家族。这些系统 使用常见的辅助因子催化不同的反应结果，由结构控制 每个酶的特征。比较方法提供详细且可测试的方法 关于实现不同化学反应的手段的假设，如 以及发现全新的酶家族以及控制他们的新方法 活动。这项工作的目的是实现催化能力 这些系统固有的，以更有效，更环保的综合 药物，化学药品，技术工具和新化学过程。