title: Inhibitor studies on phage T4 wild-type and mutant DNA polymerase. IV. The substrate analog 3'-fluorothymidine 5'-triphosphate.
abstract: The deoxythymidine-5'-triphosphate (dTTP) analog 3'-fluorothymidine 5'-triphosphate (3'-FdTTP) inhibits DNA synthesis by T4 wild-type, L98 (mutator) and CB121 (antimutator) DNA polymerase. CB121 DNA polymerase is less sensitive by a factor of two than the L98 and T4+ enzymes. Inhibition is not due to incorporation of the analog into DNA. 3'-FdTTP acts competitively to the substrate dTTP. The CB121 polymerase exhibits a higher Ki to Km ratio than the other two enzymes (5.3 vs. 3.3) and thus discriminates better between the substrate dTTP and its analog 3'-FdTTP. 3'-FdTTP inhibits the polymerase-associated 3'-5' exonuclease activities to the same extent as their polymerase activities. The CB121 3'-5' exonuclease activity is suppressed only half as much by 3'-FdTTP as by dTTP. The results are discussed in relation to the role of T4 DNA polymerase and its associated 3'-5' exonuclease in determining the accuracy of DNA replication.
mesh_terms: D004259:DNA-Directed DNA Polymerase / Q000235:genetics; D009154:Mutation; D019384:Nucleic Acid Synthesis Inhibitors; D013604:T-Phages / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D013942:Thymine Nucleotides / Q000494:pharmacology*
chemical_list: D019384:Nucleic Acid Synthesis Inhibitors; D013942:Thymine Nucleotides; C028870:3'-fluorothymidine-5'-triphosphate; D004259:DNA-Directed DNA Polymerase