Binding of N5,N10-methylene tetrahydrofolate and the inhibition of thymidylate synthesis by a folate-binding protein.
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.
D002352:Carrier Proteins / Q000378:metabolism*; D002474:Cell-Free System; D008722:Methods; D008780:Methyltransferases / Q000037:antagonists & inhibitors*; D013763:Tetrahydrofolates / Q000378:metabolism*; D013938:Thymidine Monophosphate / Q000096:biosynthesis; D013940:Thymidylate Synthase / Q000037:antagonists & inhibitors*
D002352:Carrier Proteins; D013763:Tetrahydrofolates; D013938:Thymidine Monophosphate; D008780:Methyltransferases; D013940:Thymidylate Synthase