A Protein Analog Approach to Biomimetic Studies of Metalloenzymes

伊利诺伊大学的陆毅博士获得了无机化学、生物无机化学和金属有机化学项目的支持，该项目获得了学院早期职业发展奖，以表彰对酶功能的仿生研究。定点突变将用于改变天青素和环色素c过氧化物酶等小金属蛋白的蛋白质环境，使其分别成为环色素c氧化酶和木质素过氧化物酶的功能模拟物。这项工作的主要目标是获得关于活性部位功能的结构和机械信息，这些信息对于更大、更复杂的蛋白质来说是很难或不可能获得的。将使用多种技术来研究基因工程蛋白，包括UV-Vis、EPR、MCD、核磁共振、Endor和EXAFS光谱。如有可能，将获得修饰蛋白质的X射线结构。教学计划概述了将现代研究方法引入本科实验室的方法，重点是一年级高级化学实验室。还详细介绍了在该大学最近开发的生物分子化学项目中培养研究生的计划，该项目旨在培养化学和生物学交界处的跨学科研究。对于继续享有贸易顺差的化学工业来说，一个主要挑战是开发仍然低成本、高产量、但对环境无害的新工艺。小的、设计合理的蛋白质可以用作某些过程的催化剂，因为试剂、催化剂和产品(新蛋白质)是可生物降解的，因此完全没有污染。将在该项目中进行的研究将支持这种小蛋白的最终设计。对于化学工业来说，要转换到这种制造过程，将需要在化学以外的几个领域拥有熟练的科学家。像卢博士设想的生物分子化学专业研究生的跨学科研究培训，对培养这样的高技能科学家至关重要。

Dr. Yi Lu, of the University of Illinois, is supported by the Inorganic, Bioinorganic and Organometallic Chemistry Program under a Faculty Early Career Advancement Award for biomimetic studies of enzyme function. Site directed mutagenesis will be used to alter the protein environments of small metalloproteins such as azurin and cyctochrome c peroxidase in an effort to induce them to become functional mimics of cyctochrome c oxidase and lignin peroxidase, respectively. The primary objective of this work is to obtain structural and mechanistic information about the function of the active site that is difficult or impossible to obtain for the larger, more complex proteins. A variety of techniques will be used to study the genetically engineered proteins including UV-VIS, EPR, MCD, NMR, ENDOR and EXAFS spectroscopies. When possible x-ray structures on the modified proteins will be obtained. The teaching plan outlines methods for introducing modern research methodology into undergraduate laboratories with emphasis on the first year advanced chemistry laboratory. Also detailed are plans for training graduate research students in the recently developed Biomolecular Chemistry program at the university, which aims to foster interdisciplinary research at the interface of chemistry and biology. A major challenge for the chemical industry, which continues to enjoy a favorable trade balance, is to develop new processes that are still low-cost and high yielding, but are environmentally benign. Small, properly designed proteins may serve as catalysts for certain processes, which would be entirely nonpolluting since the reagents, catalyst and products (new proteins) would be biodegradable. The studies to be conducted in this project will support the ultimate design of such small proteins. For the chemical industry to convert to such manufacturing processes will require scientists who are skilled in several areas besides chemistry. Interdisciplinary research training such as that envisioned by Dr. Lu for graduate students in the Biomolecular Chemistry program is crucial to the development of such highly skilled scientists.