Iodothyronine Deiodinase - Enzyme Structure

Enzyme Structure

The three deiodinase enzymes share certain structural features in common although their sequence identity is lower than 50%. Each enzyme weighs between 29 and 33kDa. Deiodinases are dimeric integral membrane proteins with single transmembrane segments and large globular heads. They share a TRX fold that contains the active site including the rare selenocysteine amino acid and two histidine residues. Selenocysteine is coded by a UGA codon, which generally signifies termination of a peptide through a stop codon. In point mutation experiments with Deiodinase 1 changing UGA to the stop codon TAA resulted in a complete loss of function, while changing UGA to cysteine (TGT) caused the enzyme to operate at around 10% normal efficiency. In order for UGA to be read as a selenocysteine amino acid instead of a stop codon, it is necessary that a downstream stem loop sequence, the selenocysteine insertion sequence (SECIS), be present to bind with SECIS binding protein-2 (SBP-2), which binds with elongation factor EFsec. The translation of selenocysteine is not efficient, even though it is important to the functioning of the enzyme. Deiodinase 2 is localized to the ER membrane while Deinodase 1 and 3 are found in the plasma membrane.