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: 9324290
• 负责人: Amie K Boal
• 金额: $ 38.64万
• 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 2021-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9324290
• 关键词: Active Sites; Biology; Chemicals; Complex; Data; Engineering; Enzymes; Family; Free Radicals; Glean; Individual; Outcome; Process; Proteins; Reaction; System; Therapeutic; Transition Elements; Work; antimicrobial; base; catalyst; design; enzyme structure; insight; member; metalloenzyme; non-Native; novel; novel therapeutics; scaffold; tool

Project Summary Enzymes that employ transition metals to initiate free-radical mechanisms require exquisite control of highly reactive intermediates. The mechanism by which diverse outcomes can be controlled by similar enzyme structures and active sites is not well understood. Global study of entire enzyme classes provides detailed, testable hypotheses about the means by which distinct outcomes are accomplished, providing deeper insight into the reactions catalyzed by individual members. This family-wide approach will be essential for controlling these scaffolds, both in engineering of new protein-based catalysts and in targeting these systems for novel antimicrobial therapeutics. This approach has already allowed for successful reengineering of non-native activity into a new scaffold using observations gleaned from structural data. Continued work to reveal the structural underpinnings of mechanism in complex metalloenzymes will enable exploitation of the seemingly limitless catalytic capabilities of these systems in the design of new drugs, new technological tools, and new chemical processes.

项目摘要 采用过渡金属启动自由基机制的酶需要高度控制 反应性中间体。可以通过类似酶来控制各种结果的机制 结构和主动地点尚不清楚。整个酶类的全球研究提供了详细的研究 关于实现不同结果的手段的可检验假设，提供了更深入的见解 进入个人成员催化的反应。这种家庭范围的方法对于控制至关重要 这些脚手架，包括新的基于蛋白质的催化剂的工程以及针对新型系统的新型脚手架 抗菌疗法。这种方法已经允许成功地重新设计非本地人 使用从结构数据收集的观测值进入新的脚手架。继续工作以揭示 复杂冶金酶中机制的结构基础将使看似剥削 这些系统在新药，新技术工具和新的设计中的无限催化能力 化学过程。