title: On the inhibition of deoxycytidylate hydroxymethylase by 5-fluoro-2'-deoxycytidine 5'-monophosphate.
abstract: Studies were performed to determine whether 5-fluoro-2'-deoxycytidine 5'-monophosphate (FdCMP) is an inhibitor of deoxycytidylate hydroxymethylase and whether it could form an isolable covalent complex with the enzyme and the cofactor, 5,10-methyl-enetetrahydrofolate. The results showed that although FdCMP is a competitive inhibitor of dCMP hydroxymethylase, it does not cause time-dependent inhibition of the enzyme in the presence of cofactor. Further, although uv difference spectral evidence was found for FdCMP-cofactor-enzyme complex, the complex was not sufficiently stable to isolate on nitrocellulose filters. We conclude that FdCMP is not a mechanism-based inhibitor of dCMP hydroxymethylase.
authors.affiliation: Department of Biochemistry and Biophysics, University of California, San Francisco 94143.
authors.forename: R
authors.initials: R
authors.lastname: Subramaniam
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.forename: C K
authors.initials: CK
authors.lastname: Mathews
authors.forename: D V
authors.initials: DV
authors.lastname: Santi
mesh_terms: D003568:Cytidine Monophosphate / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology* / Q000031:analogs & derivatives; D003597:Cytosine Nucleotides / Q000494:pharmacology*; D004926:Escherichia coli / Q000201:enzymology; D019877:Hydroxymethyl and Formyl Transferases; D007700:Kinetics; D011865:Radioisotope Dilution Technique; D014166:Transferases / Q000037:antagonists & inhibitors*; D014316:Tritium
chemical_list: D003597:Cytosine Nucleotides; D014316:Tritium; C061556:5-fluoro-2'-deoxycytidine 5'-monophosphate; D014166:Transferases; D019877:Hydroxymethyl and Formyl Transferases; C100226:deoxycytidylate hydroxymethyltransferase; D003568:Cytidine Monophosphate