Dinitrophenol, Dicoumarol and Pentachlorophenol as Inhibitors and Parasite Substrates in the ATP Phosphoribosyltransferase Reaction

Abstract

Adenosine‐triphosphate phosphoribosyltransferase from Escherichia coli is inhibited by dicoumarol and pentachlorophenol in competition with ATP. K i was approximately 60 μM for dicoumarol and 50 μM for pentachlorophenol. Carbonylcyanide m‐chlorophenylhydrazone did not seem to have any kinetic effect. Dicoumarol is bound to the extent of 6 sites per enzyme hexamer with a dissociation constant K d of 50 μM. Dicoumarol and pentachlorophenol partly prevent the binding of ATP and AMP to the transferase. The reversed reaction is inhibited by dicoumarol and pentachlorophenol without changes in [S] 0.5 for phosphoribosyladenosine triphosphate. Dicumarol, dinitrophcnol and pentachlorophenol diminish the yield of phosphoribosyladenosine triphosphate in the transferase reaction apparently by acting as parasite substrates; carbonylcyanide m‐chlorophenylhydrazone had no effect.