Iodothyronine deiodinases (Dios) are selenocysteine-dependent enzymes that activate and deactivate thyroid hormones through reductive elimination of iodide. Mutations at key residues can prevent deiodination to disrupt developmental and metabolic processes. Multiple μs molecular dynamics simulations using AMBER have been performed on the wild-type of Dio3 and its Ser167Ala, Thr169Ala, and Glu200Thr mutants to understand the structural effects of mutation on a critical omega-loop that is believed to contribute to substrate binding and activation. Hydrogen-bonding interactions between residues in the loop and active site define the conformation of the loop and presumably substrate selectivity and the activity of the protein. Hydrogen bonding interactions between loop residues and the side chains of the Ser167/Thr169 residues at the active site pin the loop to the bulk of the protein. Mutations of these residues significantly increase loop flexibility, which likely results in diminished substrate binding and loss of activity.<br/>

Effect of hydrogen bonding on the conformation dynamics of an Ω-loop of iodothyronine deiodinase

2019 Spring National Meeting

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