title: Triplets! Unexpected structural similarity among the three enzymes that catalyze initiation and termination of thyroid hormone effects.
abstract: The three iodothyronine deiodinases catalyze the initiation (D1, D2) and termination (D3) of thyroid hormone effects in vertebrates. A recently conceived 3-dimensional model predicts that these enzymes share a similar structural organization and belong to the thioredoxin (TRX) fold superfamily. Their active center is a selenocysteine-containing pocket defined by the beta1-alpha1-beta2 motifs of the TRX fold and a domain that shares strong similarities with the active site of iduronidase, a member of the clan GH-A fold of glycoside hydrolases. While D1 and D3 are long-lived plasma membrane proteins, D2 is an endoplasmic reticulum resident protein with a half-life of only 20 min. D2 inactivation is mediated by selective UBC-7-mediated conjugation to ubiquitin, a process that is accelerated by T4 catalysis, thus maintaining local T3 homeostasis. In addition, D2 interacts with and is a substrate of the pVHL-interacting deubiquitinating enzymes (VDU1 and VDU2); thus deubiquitination regulates the supply of active thyroid hormone in D2-expressing cells.
authors.affiliation: Thyroid Section, Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA. abianco@partners.org
authors.forename: Antonio C
authors.initials: AC
authors.lastname: Bianco
mesh_terms: D000818:Animals; D006801:Humans; D007453:Iodide Peroxidase / Q000502:physiology*; D011487:Protein Conformation; D013963:Thyroid Hormones / Q000378:metabolism*; D025801:Ubiquitin / Q000502:physiology; D000097564:Iodothyronine Deiodinase Type II
chemical_list: D007453:Iodide Peroxidase; D013963:Thyroid Hormones; D025801:Ubiquitin; D000097564:Iodothyronine Deiodinase Type II; C109812:iodothyronine deiodinase type I; C117274:iodothyronine deiodinase type III