Modest catalysis of the decarboxylation of orotate by hydrogen bonding: a theoretical model for orotidine-5′-monophosphate decarboxylase

As a model for interactions present in the active site of orotidine-5′-monophosphate decarboxylase (ODCase), the effect of hydrogen bonds to the carbonyl groups (O-2 and O-4) of orotic acid and its decarboxylation product was probed with ab initio calculations. We have found that the transition state/carbanion intermediate is a better proton receptor and therefore, the hydrogen bonds can be a modest source of catalysis. Comparison of the calculated data with results from site-directed mutagenesis provides some insights into the polarity of the active site.