Fig. 1. Inhibitor 5-fluoro-2′-deoxyzebularine (FdZ) embedded in hairpin DNA is hydrolyzed to form a tetrahedral species coordinated to Zn²⁺ of wildtype A3A.

a Schematic of reaction of FdZ with water activated by Zn²⁺, analogous to that of cytidine/cytosine deaminases, showing critical role of general acid-base Glu72. b Schematic of TTFdZ- and TTC-hairpins. c Structure of wildtype A3A (yellow) in complex with TTFdZ-hairpin inhibitor (orange). Carbon atoms of nucleotides of the TTFdZ loop are shown in salmon-pink, ligands to the Zn²⁺ center and key protein residues interacting with TTFdZ-hairpin in cyan. d Zoomed-in structure of wildtype A3A with TTFdZ-hairpin inhibitor highlighting the hydrolyzed FdZ⁰ coordinated to the active-site Zn²⁺ and hydrogen bonding to Glu72 (cyan).