Mol. Biosyst.; doi:10.1039/c3mb70398c

Credit: ABHISHEK PHATARPHEKAR

Thyroid hormone is a multiply iodinated, tyrosine-based molecule that regulates metabolism. Iodotyrosine deiodinase (IYD) takes part in thyroid hormone synthesis by salvaging iodide from mono- and diiodotyrosine via reductive dehalogenation. To learn more about IYDs throughout biology, Phatarphekar et al. searched for new enzymes using a unique lid structure along with several active site residues as clues. Bioinformatics identified a number of sequences, from which the authors expressed and characterized seven new enzymes; in each case, kcat/Km values for the deiodination of monoiodotyrosine were within an order of magnitude of the known mouse homolog. The authors also noted that the annotations for some of the nonmammalian enzymes were incomplete or absent, presumably because other species have no obvious use for this enzyme. However, the authors postulate that the presence of IYD in honeybee and daphnia could be linked to reports that these species can obtain thyroid hormone exogenously. Jellyfish (related to the hydra and sea anemone proteins studied here) have previously been shown to initiate developmental changes in response to iodotyrosine or thyroid hormone, suggesting these enzymes may have unexpected regulatory roles. Finally, the more than 200 bacterial sequences may have roles in detoxification. The appropriate description of these enzymes offers new opportunities to understand the role of iodine in biological systems.