Fig. 3. M06-2X/MM optimized structures of the key states of the acylation (top panels) and deacylation (bottom panels): E:S, rate determining TS of the acylation TSE:S→E-I1, TSE:S→E-I2, TSE-I2→E-I3, E-I2, rate determining TS of the deacylation TSE:I2→E-I3, and TSE:S→E-I2. Distances are in Å.