Mapping the structural basis for mechanistic diversity in metalloenzyme superfamilies

项目摘要 利用过渡金属来启动自由基机制的酶需要精细地控制高度的 活性中间体相似酶控制不同结果的机制 结构和活性位点还不清楚。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检验假设，提供更深入的见解 转化为单个成员催化的反应。这种全家族的方法对于控制 这些支架，无论是在新的蛋白质为基础的催化剂工程，并在针对这些系统的新的 抗微生物疗法。这种方法已经允许成功地重新设计非本地 使用从结构数据收集的观察结果将活性转移到新的支架中。继续努力揭示 复杂的金属酶的结构基础机制将使开发的表面上 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.