A common feature between the two A3A–ssDNA complex structures is that the ssDNA forms a “U” shape in the active site (Fig. 5c,d)20,22. This U shape of the bound polynucleotide may be conserved among deaminases, including adenosine deaminases20,34. In both A3A–ssDNA structures, the U shape of the ssDNA orients the −2 and +1 bases in close proximity to each other. Thus, we hypothesized that the observed sequence preference (Fig. 3) for the −2 position is a result of intra-DNA interactions rather than specific interactions with the protein.