title: Efficient use and recycling of the micronutrient iodide in mammals.
abstract: Daily ingestion of iodide alone is not adequate to sustain production of the thyroid hormones, tri- and tetraiodothyronine. Proper maintenance of iodide in vivo also requires its active transport into the thyroid and its salvage from mono- and diiodotyrosine that are formed in excess during hormone biosynthesis. The enzyme iodotyrosine deiodinase responsible for this salvage is unusual in its ability to catalyze a reductive dehalogenation reaction dependent on a flavin cofactor, FMN. Initial characterization of this enzyme was limited by its membrane association, difficult purification and poor stability. The deiodinase became amenable to detailed analysis only after identification and heterologous expression of its gene. Site-directed mutagenesis recently demonstrated that cysteine residues are not necessary for enzymatic activity in contrast to precedence set by other reductive dehalogenases. Truncation of the N-terminal membrane anchor of the deiodinase has provided a soluble and stable source of enzyme sufficient for crystallographic studies. The structure of an enzyme.substrate co-crystal has become invaluable for understanding the origins of substrate selectivity and the mutations causing thyroid disease in humans.
authors.affiliation: Department of Chemistry & Biochemistry, University of Maryland, College Park, MD 20742, USA. rokita@umd.edu
authors.forename: Steven E
authors.initials: SE
authors.lastname: Rokita
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Adler
authors.forename: Patrick M
authors.initials: PM
authors.lastname: McTamney
authors.forename: James A
authors.initials: JA
authors.lastname: Watson
mesh_terms: D000818:Animals; D006801:Humans; D007453:Iodide Peroxidase / Q000235:genetics / Q000378:metabolism; D007454:Iodides / Q000378:metabolism*; D018977:Micronutrients / Q000378:metabolism; D016297:Mutagenesis, Site-Directed; D013961:Thyroid Gland / Q000378:metabolism
chemical_list: D007454:Iodides; D018977:Micronutrients; D007453:Iodide Peroxidase