Figure 1: Recognition of the deamination target sequences.

a) Apo-form structure of the A3G-CTD (PDB ID: 2KEM). Electrostatic surface distribution showing positive (+5 kT/e, blue) and negative (−5 kT/e, red) regions. Helices and strands are labeled, and sidechains of His257, Glu259, Cys288 and Cys291 are shown as stick model. Zn²⁺ ion is shown as a purple sphere. b) Co-crystal structure of A3A with ssDNA (PDB ID: 5KEG). Three nucleotides of the deamination target ssDNA bound as U-shaped conformations. c) Co-crystal structure of a A3G catalytic domain variant (CTD2*) with ssDNA (PDB ID: 6BUX). ssDNA have more open and extended shape providing extra interaction with protein. In both A3A and A3G-CTD2*, the target cytosine (C⁰) is flipped out, and tightly packed under the Zn²⁺ ion by stacking aromatic rings with the Zn²⁺-chelating residue His70 and His257 in A3A and A3G, respectively. Proteins are represented as yellow cartoons; C, N, and O atoms are colored yellow, blue, and red, respectively, for amino acid residues of the protein. DNAs are represented as cartoons; nucleotides are colored blue and phosphate backbone are colored orange. d) and e) Summary of interactions between protein and ssDNA for A3A and A3G-CTD2*, respectively. f) Sequence alignment and structural representation of active site loops in APOBEC3 family. The sequence alignments of active site loops in A3 family are mapped on the ssDNA bound A3A crystal structure (PDB: 5KEG). The sequence similarity is colored according to figure legend.