Is Halogen Bonding the Basis for Iodothyronine Deiodinase Activity?

Abstract

Density functional theory studies of S...X and Se...X (X = Br, I) halogen-bonding interactions are used to interpret the selection of selenium and iodine for thyroid hormone signaling. A new mechanism for dehalogenation in terms of halogen bonding is proposed. The activation barriers for deiodination of an aromatic iodide by MeSeH and MeSH (17.6 and 19.8 kcal/mol) are consistent with the relative rates of deiodination by iodothyronine deiodinase and its cysteine mutant.