Endocrinology, Vol 129, 550-552, Copyright © 1991 by Endocrine Society

ARTICLES

Evidence that cysteine, not selenocysteine, is in the catalytic site of type II iodothyronine deiodinase

MJ Berry, JD Kieffer and PR Larsen
Department of Medicine, Brigham and Women's Hospital, Boston.

Recent cloning of the cDNA for Type I iodothyronine deiodinase revealed that the mRNA contains a UGA codon encoding the amino acid selenocysteine. Mutagenesis of the selenocysteine codon to a cysteine codon produced a protein with lower deiodinase activity. The presence or absence of selenocysteine in Type II deiodinase, which differs from the Type I enzyme in a number of parameters, has not been determined. Gold inhibits the activity of both the Type I deiodinase and the only other known eukaryotic selenocysteine-enzyme, glutathione peroxidase. Substitution of cysteine for selenocysteine in Type I deiodinase reduced its sensitivity to inhibition by gold 500-fold. We found that gold thioglucose was a competitive inhibitor with respect to the iodothyronine substrate of both deiodinases. However, the Type II enzyme from brown fat and pituitary was 100 to 1000-fold less sensitive to gold than was Type I activity in liver and pituitary, similar to the results with the cysteine-substituted Type I enzyme. This suggests that Type II deiodinase contains cysteine instead of selenocysteine in the active site.

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