Reductive deiodination of mono- and diiodotyrosine is promoted by iodotyrosine deiodinase (IYD) and its bound cofactor, flavin mononucleotide (FMN and, in its reduced form, FMNH2).

Active site region of iodotyrosine deiodinase from mouse is established by both subunits of its α2 dimer (preen and purple) and contains flavin (FMN), monoiodotyrosine (MIT) and the key residues stabilizing their complex (PDB ID 3GFD).

Multiple sequence alignment of the catalytic domains of IYD homologs. Alignment of homologs chosen for protein expression was generated using MUSCLE.45 Numbering of the amino acids for each protein is indicated on the left and right of the alignment. Residues in red (or white) are fully conserved, and the sequences forming the active site lids are indicated with a box. Key residues coordinating to substrate and FMN are indicated with an (*) and (+), respectively. Secondary structure elements are derived from the crystal structure of mmIYD bound to DIT (PDB ID 3GH8).11

The tree of life. A tree indicating the diversity of organisms in which IYD homologs were identified and chosen for expression. Phylum and class for each organism were obtained from the NCBI taxonomy browser.46 Branches are not drawn to scale.

Phylogenetic analysis focusing on the IYD branch of the nitro-FMN reductase superfamily. A phylogenetic tree was generated by phylogeny.fr47 integrating MUSCLE,45 PhyML,48 and TreeDyn49 for multiple sequence alignment, phylogenetic analysis and tree rendering, respectively. Catalytic domains of IYD homologs and aligned regions of BluB (PDB ID 2ISJ), NOX (PDB ID 1NOX) and FRP (PDB ID 2BKJ) were used as input sequences. The branch lengths are proportional to the number of amino acid substitutions per aligned residue.