A Protein Analog Approach to Biomimetic Studies of Metalloenzymes

伊利诺伊大学的Yi Lu博士获得了无机、生物无机和有机金属化学项目的支持，该项目获得了学院早期职业发展奖，主要研究酶功能的仿生研究。位点定向诱变将用于改变小金属蛋白如azurin和cytochromec过氧化物酶的蛋白质环境，以诱导它们分别成为cytochromec氧化酶和木质素过氧化物酶的功能模拟物。这项工作的主要目的是获得有关活性位点功能的结构和机制信息，这些信息对于更大、更复杂的蛋白质来说很难或不可能获得。多种技术将用于研究基因工程蛋白，包括UV-VIS， EPR， MCD， NMR， ENDOR和EXAFS光谱。在可能的情况下，将获得修饰蛋白的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，重点是第一年的高级化学实验室。此外，还详细介绍了首尔大学最近开设的生物分子化学专业研究生培养计划，该专业旨在培养化学和生物学交叉领域的研究。化学工业继续享有有利的贸易平衡，它面临的一个主要挑战是开发成本低、产量高、但对环境无害的新工艺。适当设计的小蛋白质可以作为某些过程的催化剂，这将是完全无污染的，因为试剂、催化剂和产品（新蛋白质）将是可生物降解的。在这个项目中进行的研究将支持这种小蛋白质的最终设计。化学工业要转变为这种制造工艺，就需要在化学以外的几个领域都很熟练的科学家。陆博士为生物分子化学专业研究生提供的跨学科研究培训对培养这些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.