An Unprecedented Twist to ODCase Catalytic Activity

Orotidine-5‘-monophosphate decarboxylase (ODCase) has evolved to catalyze a decarboxylation reaction, most probably via a carbanion species at the C6 position of orotidine-5‘-monophosphate. We reveal an unusual biochemical pathway of conversion of 6-cyano-uridine-5‘-monophosphate by ODCase to barbiturate-5‘-monophosphate via perhaps an electrophilic center at the C6 position, leading to inhibition. This potential of ODCase is very useful in the design of novel inhibitors.