Fig. S1.

Optimized structures of the reactant state in its two conformations with respect to rotation of Glu104 (Ra and Rb), the transition state for cytidine protonation (TS1), and the protonated cytidine intermediate (Int1). Calculations were done at the B3LYP/6-31G(d,p) level of theory with the LANL2DZ pseudopotential for the zinc ion. The substrate is highlighted with orange carbons (nonpolar hydrogens omitted and distances in Å). Constrained atoms in the DFT optimizations are indicated with asterisks.