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.

项目总结