ADAT1 is a homodimeric enzyme and shares conserved sequence motifs with other well-characterized adenosine deaminases, including mammalian mRNA deaminases (ADARs). Also, like most members of the deaminase superfamily, a Zn2+ ion is coordinated by a conserved histidine and two cysteines. The fourth ligand is an active water molecule that acts as the nucleophile. Highly conserved glutamate then aids the reactions by shuttling a proton from water to the N1 position of inosine during the deamination reaction. These motifs constitute the canonical deaminase signature (C/H)xExnPCxxC found in most nucleotide deaminases. Tad1 (ADAT1) catalyzes the A-to-I deamination which is the first step in m1I synthesis in tRNA position 37 (Paris et al. 2011 ).