RUI: The Sources of Substrate Specificity in Hydroquinone Dioxygenases

Whitman College, Walla Walla WA

Investigators

Abstract

This award in the Chemistry of Life Processes (CLP) program, co-funded with the Division of Molecular and Cellular Biosciences (MCB), supports work by Professor Tim Machonkin at Whitman College to understand the fundamental determinants of how certain enzymes bind and carry out chemical transformations on chlorinated hydroquinones. Some bacteria have the remarkable ability to break down stable aromatic compounds, including in rare cases chlorinated aromatics. Certain types of iron-containing enzymes are involved in these processes. Among the least studied are ones that specifically recognize and cleave chlorinated hydroquinones. These hydroquinone dioxygenases appear to have evolved recently to degrade synthetic compounds that entered the environment from human activity. The factors that determine how these enzymes specifically recognize and carry out the ring-cleaving reaction on chlorinated hydroquinones are unknown. Thus, hydroquinone dioxygenases provide an ideal platform for learning how proteins can specifically bind chlorinated molecules and activate them for chemical transformations, as well as how metalloenzymes (such as iron-containing ring-cleaving enzymes) evolve new functions. This work will immerse a significant number of undergraduate students in cutting-edge biochemical research involving an array of techniques, promoting the integration of teaching and research at this primarily undergraduate institution. The knowledge gained from this research could be applied to other classes of iron-containing enzymes involved the breakdown of aromatic molecules, and could lead to engineering of enzymes with novel properties. This, in turn, could lead to improved methods for bioremediation of chlorinated aromatic molecules, which are common intractable environmental pollutants.