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 使用过渡金属的酶可以启动具有化学挑战性的修饰 惰性化学键。这些系统既是重要的药物靶点，也是有用的 生物催化剂。在某些过渡金属驱动的基本生物转变中，如 作为DNA的生物合成，发散的微量元素可用于反应的引发。 用于这些过程的新型金属辅因子的发现及其作用机理 组装和部署，将使细菌中酶抑制的新途径成为可能 病原体。在第二个项目中，三种不同的结构和反应机理 与生物催化有关的金属酶超家族将被阐明。这些系统 使用共同的辅因子催化不同的反应结果，由结构控制 每种酶的特性。比较方法提供了详细且可测试的 关于完成不同化学反应的方法的假设，如 以及发现了全新的酶家族和控制它们的新方法 活动。这项工作的目标是使催化能力得以开发。 这些系统中固有的，用于更有效和环境友好的合成 药物、化学品、技术工具和新的化学工艺。