Structure-Function Correlations in a Type III Extradiol Dioxygenase

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With this award, the Chemistry of Life Processes Program in the Chemistry Division and the Molecular Biophysics Cluster in the Molecular and Cellular Biology Division are funding Dr. Aimin Liu from Georgia State University to characterize 3-hydroxyanthranilate-3,4-dioxygenase (HAO). This enzyme performs oxidative ring-cleavage at the meta position of six-membered aromatic rings in a reaction known as extradiol dioxygenation. HAO is a prototypic member of extradiol dioxygenases built upon a cupin structural fold (known as type III extradiol dioxygenases). The goal of this project is to study the substrate recognition, oxygen binding, activation, selective targeting, and to identify the intermediates of the reactions catalyzed by HAO. Furthermore, the Liu lab seeks to identify the role of an additional rubredoxin-like Fe(Cys)4 center of the enzyme, which is not required for catalysis but is conserved in bacterial enzymes. The research aims to build a framework for understanding the mechanism of these enzymes and common steps shared by extradiol dioxygenases. The chemical, structural, and spectroscopic properties of iron-bound oxygenated intermediates will help illuminate iron-dependent oxygen activation and oxidation mechanisms. The incorporation of molecular oxygen into organic molecules is one of the most important metabolic processes in nature and its ultimate purpose is energy extraction. The Liu laboratory studies the mechanism by which a particular enzyme accomplishes this task. Knowledge created by the lab advances the understanding of oxygen activation and its specific incorporation into metabolites. The scientific questions are answered by using biochemical methods, spectroscopic tools, X-ray crystallography, and computational modeling. This multidisciplinary pursuit creates substantial opportunities to engage science students, including members of groups underrepresented in science, in research at the frontier of chemistry and biology. The knowledge gleaned from the research are incorporated in the biochemistry and bioinorganic chemistry curriculum.