人工金属蛋白酶兼备天然蛋白及修饰辅基的活性功能，一直是化学生物学的一个重要研究领域。最近本课题组关于突变体肌红蛋白L29E Mb核酸水解酶功能的首次报道，为肌红蛋白作为核酸酶应用奠定了基础，但其活性效率及可调控性等均有待进一步提高。基于国内外研究现状及申请人研究基础，本项目拟设计并合成系列新型Cu/Ru基金属中心锌卟啉辅基，进而与脱辅基肌红蛋白apo-Mb及本课题组设计的脱辅基突变体蛋白apo-L29E Mb进行体外重组，从而获得不同于天然蛋白酶的具有铜/钌-锌多金属活性中心的新型人工金属蛋白（Cu/Ru-ZnPP-apo-Mbs），研究其性质及探索其光诱导核酸酶功能。本项目旨在构建新型人工金属蛋白酶，拓展天然蛋白酶的结构与功能，深入探索金属蛋白酶的SPRF关系，为新功能人工肌红蛋白的构建提供有价值的借鉴。

Artificial metalloenzymes combine the advantages of both natural enzymes and chemically synthesized model, which is an important aspect in chemical biology in recent years.Recently,DNA hydrolytic cleavage caused by L29E Mb has been reported for the first time by our group.This study suggests that it is possible to fine-tune the diverse function of heme proteins by rational design of the heme active center.Although new progress has been made in molecular design of artificial metalloproteins, both the catalytic efficient and the controllability need to be improved further. Based on the current progress as well as the achievement in our group, this project plans to design and synthesis new zinc porphyrin modified by Cu/Ru complexes.These new zinc porphyrin derivatives will be further reconstituted with apo-myoglobin (apo-Mb) and apo-L29E Mb that was designed by our group, named Cu/Ru-ZnPP-apo-Mbs. We will study the structure, property and light-driven nuclease activity of these new artificial metallproteins.This project aims at designing and constructing new artificial metalloproteins, expanding the structure and function of natural enzymes, and deeply investigating the SPRF of metalloproteins, thereby providing a scientific example for molecule design of functional metalloenzymes.