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.

项目概要 使用过渡金属启动自由基机制的酶需要对高度精确的控制 反应中间体。相似的酶可以控制不同结果的机制 结构和活性位点尚不清楚。对整个酶类别的全球研究提供了详细的、 关于实现不同结果的方法的可检验假设，提供更深入的见解 进入由个体成员催化的反应。这种家庭范围内的方法对于控制 这些支架，无论是在新的基于蛋白质的催化剂的工程中，还是针对这些系统的新型催化剂 抗菌疗法。这种方法已经可以成功地对非本地人进行重新设计 使用从结构数据收集的观察结果将活性转化为新的支架。继续努力揭示 复杂金属酶机制的结构基础将使看似的开发成为可能 这些系统在新药、新技术工具和新产品设计中具有无限的催化能力 化学过程。