Biosynthesis of Protein-Derived Cofactors
The goal of this project is to understand the synthesis and function of protein-derived cofactors in proteins. The principal tool of the research is macromolecular X-ray crystallography. The project involves freeze-trapping reaction intermediates in the crystal to yield molecular “snapshots” along the reaction pathways generated through interrogation by X-rays. These can be assembled into “movies of catalysis” at the molecular level. By understanding these reactions in such detail, it is hoped that better drugs can be designed, proteins can be rationally engineered for biotechnological purposes, and chemists can design simpler industrial catalysts to control analogous reactions. Specific topics of interest to the Wilmot lab include structural enzymology involving assembly of the cofactors tryptophan tryptophylquinone of methylamine dehydrogenase, cysteine tryptophylquinone of glycine oxidase and pyrroloquinoline quinone of alcohol dehydrogenases.
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