Iodide-Salvaging Enzyme Analyzed Structurally

Crystal structures of mammalian iodotyrosine deiodinase (IYD), an enzyme required for the efficient use of dietary iodide, have been determined by a University of Maryland research team (J. Biol. Chem., DOI: 10.1074/
jbc.M109.013458). The work provides a deeper molecular-level understanding of how the enzyme functions and how IYD mutations can cause disease. Iodide is essential for producing the thyroid hormone thyroxine, which helps control metabolism, growth, and development. Insufficient dietary iodide intake, or IYD mutations that make the enzyme unable to recycle iodide, can cause hypothyroidism, a condition that can result in mental impairment. To conserve iodide, IYD works in conjunction with the cofactor flavin mononucleotide (FMN) to recover and reuse iodide from by-products of thyroxine biosynthesis. Nicole LaRonde-LeBlanc, Steven E. Rokita, and coworkers have now obtained the first crystal structures of the dimeric enzyme with and without its substrates, iodotyrosine and diiodotyrosine. The structures reveal that known disease-causing mutations are located in regions that surround the enzyme-bound FMN cofactor. They also reveal structural features that explain how the enzyme selects for its tyrosine-based substrates and avoids removing iodide from thyroxine.