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. Ki 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 Kd 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. Copyright © 1976, Wiley Blackwell. All rights reserved