Effect of water molecules on the decarboxylation of Orotidine 5′-monophosphate catalyzed by Orotidine 5′-monophosphate decarboxylase

The effect of water molecules on the enzyme-catalyzed decarboxylation of Orotidine 5′-monophosphate was investigated using hybrid Density Functional Theory (B3LYP functional). Different models were designed and the reaction barriers with these models were calculated. The results show that the indirect interactions between O-2 and O-4 of the pyrimidine ring and the positive charged residues through water bridges can reduce the barrier significantly; and that water molecules play a key role in the transition state stabilization of catalytic decarboxylation of Orotidine 5′-monophosphate.