Abstract
Deiodinases catalyze the specific removal of iodine atoms from one of the two
iodinated phenyl rings in iodothyronines. They thereby fine-regulate local
thyroid hormone concentrations in organs or cells. The chemical reaction is
unique in the sense that in metazoans the reductive elimination of iodide
depends on the rare amino acid selenocysteine in the enzymes’ active
centers. While there is no prokaryotic homologue of such deiodinases, the
solution of the crystal structure of a catalytic domain of mouse deiodinase 3
has revealed that the ancient peroxiredoxin structure has been repurposed, and
improved using selenocysteine, as a deiodinase during metazoan evolution.
Likewise, many biochemical findings obtained over decades can now be interpreted
in light of the molecular structure. Despite this leap in our understanding of
deiodinase structure, there are still several open questions that need to be
addressed in order to fully understand substrate binding, catalytic mechanism,
and regulation of deiodinases. We surmise that these issues as well as
differences between the three highly homologous isoenzymes must be understood in
order to develop modulators of deiodinases that could be valuable in clinical
use.
Key words
thyroid hormone - metabolism - dehalogenation - catalysis
