Editing Iodothyronine deiodinase (section)

== 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.<ref name="pmid18815314"/>  Deiodinases are dimeric [[integral membrane proteins]] with single transmembrane segments and large globular heads (see below).<ref name="url_Bianco_Lab">{{cite web | url = http://deiodination.org/ | title = Thyroid hormone action starts and ends by deiodination  | author = Bianco AC | publisher = Bianco Lab & The University of Miami | access-date = 2011-05-08 }}</ref> They share a TRX fold that contains the [[active site]] including the rare selenocysteine amino acid and two [[histidine]] residues.<ref name="pmid18815314"/><ref name="pmid9002998">{{cite journal | vauthors = Valverde C, Croteau W, Lafleur GJ, Orozco A, Germain DL | title = Cloning and expression of a 5'-iodothyronine deiodinase from the liver of Fundulus heteroclitus | journal = Endocrinology | volume = 138 | issue = 2 | pages = 642–8 | date = February 1997 | pmid = 9002998 | doi = 10.1210/endo.138.2.4904 | doi-access = free }}</ref>  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.<ref name="pmid1825132">{{cite journal | vauthors = Berry MJ, Banu L, Larsen PR | title = Type I iodothyronine deiodinase is a selenocysteine-containing enzyme | journal = Nature | volume = 349 | issue = 6308 | pages = 438–40 | date = January 1991 | pmid = 1825132 | doi = 10.1038/349438a0 | bibcode = 1991Natur.349..438B | s2cid = 4338963 }}</ref>  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.<ref name="pmid18815314"/> The translation of selenocysteine is not efficient,<ref name="pmid9292958">{{cite journal | vauthors = St Germain DL, Galton VA | title = The deiodinase family of selenoproteins | journal = Thyroid | volume = 7 | issue = 4 | pages = 655–68 | date = August 1997 | pmid = 9292958 | doi = 10.1089/thy.1997.7.655 }}</ref> even though it is important to the functioning of the enzyme.  Deiodinase 2 is localized to the ER membrane while Deiodinase 1 and 3 are found in the plasma membrane.<ref name="pmid18815314"/>

The related catalytic domains of Deiodinases 1-3 feature a thioredoxine-related peroxiredoxin fold.<ref name=PMID25002520>{{cite journal | vauthors = Schweizer U, Schlicker C, Braun D, Köhrle J, Steegborn C | title = Crystal structure of mammalian selenocysteine-dependent iodothyronine deiodinase suggests a peroxiredoxin-like catalytic mechanism | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 111 | issue = 29 | pages = 10526–31 | date = July 2014 | pmid = 25002520 | pmc = 4115520 | doi = 10.1073/pnas.1323873111 | bibcode = 2014PNAS..11110526S | doi-access = free }}</ref> The enzymes catalyze a reductive elimination of iodine, thereby oxidizing themselves similar to Prx, followed by a reductive recycling of the enzyme.