Inhibition of orotidine-5'-phosphate decarboxylase by 1-(5'-phospho-.beta.-D-ribofuranosyl)barbituric acid, 6-azauridine 5'-phosphate, and uridine 5'-phosphate

Abstract

1-(5'-Phospho-beta-D-ribofuranosyl)barbituric acid, an analogue of orotidylic acid, binds to orotidine-5'-phosphate decarboxylase about 100000 times as strongly as does the substrate. The Ki at pH 6 is 9 X 10(-12) M and the half-time for dissociation at 4 degrees C is about 10 h. The binding of the barbiturate analogue to the enzyme is thus one of the strongest interactions between small molecules and proteins that have been measured. The possibility that the inhibitor is a transition-state analogue is discussed.