The mechanism of the transacylation reaction of methyl acetate with methoxide has been explored using density functional theory (B3LYP/6-31+G(d)) and PCM-UAKS solvation models. The conformations of all of the transition states and intermediates are strongly influenced by the anomeric effect. The conformations of phosphonates were computed and analyzed. The bound inhibitors obtained from X-ray crystallographic structures of lipases and esterases adopt a few specific conformations. The conformers of the transition states and intermediates in transacylations are compared to the conformations of the phosphonate inhibitors. Although the energy differences are small, the frequency of the occurrence of the phosphonate conformers in crystal structures is more closely related to the relative energies of free phosphonate conformers than to the relative energies of acylation transition states.