The three iodothyronine deiodinases catalyze the initiation (D1, D2) and termination (D3) of THyroid hormone effects in vertebrates. A 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 β1-α1-β2 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 D 1 and D3 are long-lived plasma membrane proteins (t 1/2 10-12 h), D2 is an endoplasmic reticulum resident protein that is inactivated by selective conjugation to ubiquitin, a process that is mediated by WSB-1, a Hedgehog-inducible gene. Remarkably, D2 ubiquitination is reversible and activity restored after deubiquitination by the pVHL-interacting deubiquitinating enzymes (VDU1 and VDU2). Deiodinases play a major role in development as well as in adults as critical players in Thyroid hormone homeostasis, particularly during hypo- and hyper Thyroidism. In addition to playing an important part in energy homeostasis, changes in deiodinase activity explain the alterations in Thyroid economy observed during illness and in the recently described syndrome of consumptive hypo Thyroidism.
|Original language||English (US)|
|Title of host publication||Selenium|
|Subtitle of host publication||Its Molecular Biology and Role in Human Health, Second Edition|
|Number of pages||13|
|ISBN (Print)||0387338268, 9780387338262|
|State||Published - Jan 1 2006|
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