On the inhibition of deoxycytidylate hydroxymethylase by 5-fluoro-2'-deoxycytidine 5'-monophosphate.
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.
Subramaniam
R
R
Department of Biochemistry and Biophysics, University of California, San Francisco 94143.
Wang
Y
Y
Mathews
C K
CK
Santi
D V
DV
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
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