A Protein Analog Approach to Biomimetic Studies of Metalloenzymes

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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.