Binding of N5,N10-methylene tetrahydrofolate and the inhibition of thymidylate synthesis by a folate-binding protein

Abstract

A mixture of two ionic forms of a folate-binding protein purified from chronic myelogenous leukemia cells reversibly binds N5,N10-methylene tetrahydrofolate and prevents the coupling of this cofactor to thymidylate synthetase in a terniary complex with fluorodeoxyuridylate. The binding protein also inhibits the enzymic synthesis of thymidine monophosphate by preventing the methylation of deoxyuridylate. These findings suggest that one function of the folate-binding protein may be to regulate the intracellular concentration of free folate cofactors and, thereby, modulate their functional activity.