Interaction of Epstein-Barr virus DNA polymerase with aphidicolin, phosphonoformate and 5'-GMP.
Epstein-Barr virus (EBV)-specified DNA polymerase was purified from P3HR-1 cells, a Burkitt lymphoma EBV producer cell line, treated with phorbol-12,13-dibutyrate (PDB) and n-butyrate. Its inhibition by aphidicolin, phosphonoformate (PFA) and 5'-GMP was examined. Aphidicolin could inhibit EBV DNA polymerase competitively with respect to dATP and dCTP and noncompetitively with respect to dGTP and dTTP; whereas 5'-GMP was a noncompetitive inhibitor with respect to all four dNTPs. Combinations of aphidicolin and PFA, or PFA and 5'-GMP, produced a mutually exclusive inhibition pattern of EBV DNA polymerase that suggested that the binding sites of these compounds on the enzyme molecule are kinetically overlapping.
Li
J S
JS
Department of Pharmacology, School of Medicine, University of North Carolina, Chapel Hill 27599-7365.
Cheng
Y C
YC
D016590:Aphidicolin; D003854:Deoxyribonucleotides / Q000378:metabolism; D004224:Diterpenes / Q000494:pharmacology*; D017245:Foscarnet; D006150:Guanine Nucleotides / Q000494:pharmacology*; D006157:Guanosine Monophosphate / Q000494:pharmacology*; D004854:Herpesvirus 4, Human / Q000201:enzymology*; D019384:Nucleic Acid Synthesis Inhibitors; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D010746:Phosphonoacetic Acid / Q000031:analogs & derivatives / Q000494:pharmacology*; D011485:Protein Binding; D014764:Viral Proteins / Q000037:antagonists & inhibitors*
D003854:Deoxyribonucleotides; D004224:Diterpenes; D006150:Guanine Nucleotides; D019384:Nucleic Acid Synthesis Inhibitors; D009943:Organophosphorus Compounds; D014764:Viral Proteins; D017245:Foscarnet; D016590:Aphidicolin; D006157:Guanosine Monophosphate; D010746:Phosphonoacetic Acid