The three iodothyronine selenodeiodinases catalyze the initiation and termination of thyroid hormone ef- fects in vertebrates. Structural analyses of these pro- teins have been hindered by their integral membrane nature and the inefficient eukaryotic-specific pathway for selenoprotein synthesis. Hydrophobic cluster analy- sis used in combination with Position-specific Iterated BLAST reveals that their extramembrane portion be- longs to the thioredoxin-fold superfamily for which ex- perimental structure information exists. Moreover, a large deiodinase region imbedded in the thioredoxin fold shares strong similarities with the active site of iduronidase, a member of the clan GH-A-fold of glyco- side hydrolases. This model can explain a number of results from previous mutagenesis analyses and permits new verifiable insights into the structural and func- tional properties of these enzymes.

The Iodothyronine Selenodeiodinases Are Thioredoxin-fold Family Proteins Containing a Glycoside Hydrolase Clan GH-A-like Structure.

Isabelle Callebaut, Cyntia Curcio-Morelli, Jean-P. Mornon, Balazs Gereben, Christoph Buettner, Stephen Huang, Bertrand Castro, Tatiana L. Fonseca, John W. Harney, P. Reed Larsen, and Antonio C. Bianco. Journal of Biological Chemistry. July 7, 2003. doi: 10.1074/jbc.M305725200

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