Mapping the structural basis for mechanistic diversity in metalloenzyme superfamilies

项目摘要 使用过渡金属来启动自由基机制的酶需要对高度 活性中间体。由相似的酶控制不同结果的机制 结构和活性部位还没有被很好地理解。对整个酶类的全球研究提供了详细的、 关于实现不同结果的方法的可测试假设，提供更深入的洞察力 转化为由个别成员催化的反应。这种全家庭范围的方法对于控制 这些支架，无论是在设计新的基于蛋白质的催化剂方面，还是在针对这些系统的新的 抗菌疗法。这种方法已经允许成功地对非本机的 利用从结构数据中收集的观察数据，将活动引入新的脚手架。继续工作以揭示 复杂金属酶机制的结构基础将使看似 这些系统在设计新药、新技术工具和新技术方面的无限催化能力 化学过程。

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.