R. Langenbach, P. Danenberg, C. Heidelberger
Sep 26, 1972
Citations
3
Influential Citations
190
Citations
Quality indicators
Journal
Biochemical and biophysical research communications
Abstract
Abstract Inhibition of thymidylate synthetase by 5-fluoro-2′-deoxyuridylate requires methylenetetrahydrofolate. Both 5-fluoro-2′-deoxyuridylate and methylenetetrahydrofolate are covalently bound to the enzyme, as shown by the stability of the complex to denaturation by sodium dodecyl sulfate and urea, and to trichloroacetic acid precipitation. By contrast, 5-trifluoromethyl-2′-deoxyuridylate is not covalently bound. We postulate that in the enzyme-inhibitor-cofactor complex, the 6-carbon of 5-fluoro-2′-deoxyuridylate is bound covalently to the enzyme, with the methylene group covalently linking to the 5-carbon of the nucleotide to either the N-5 or N-10 position of tetrahydrofolate.