Inhibition of a DNA polymerase from Bacillus subtilis by hydroxyphenylazopyrimidines.
The antimicrobial agent, 6-(p-hydroxyphenylazo)-uracil, specifically inhibits DNA polymerase III of Bacillus subtilis with a K(i) of less than 1 muM. The inhibition requires prior reduction of the drug, is reversible, and is competitive with dGTP. High amounts of dATP prevent inhibition by the closely related drug, 6-(p-hydroxyphenylazo)-isocytosine. A model is presented in which the inhibitors base-pair with the template while part of a ternary complex with the enzyme. These results imply that DNA polymerase III of B. subtilis is necessary for chromosomal replication.
D000255:Adenosine Triphosphate / Q000494:pharmacology; D001391:Azo Compounds / Q000037:antagonists & inhibitors / Q000494:pharmacology; D001412:Bacillus subtilis / Q000201:enzymology*; D004254:DNA Nucleotidyltransferases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004269:DNA, Bacterial / Q000378:metabolism; D004229:Dithiothreitol / Q000494:pharmacology; D006160:Guanosine Triphosphate / Q000378:metabolism / Q000494:pharmacology; D007700:Kinetics; D010636:Phenols / Q000037:antagonists & inhibitors / Q000494:pharmacology; D011119:Polynucleotides / Q000037:antagonists & inhibitors / Q000378:metabolism; D013698:Templates, Genetic; D013942:Thymine Nucleotides / Q000378:metabolism; D014316:Tritium; D014498:Uracil / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D001391:Azo Compounds; D004269:DNA, Bacterial; D010636:Phenols; D011119:Polynucleotides; D013942:Thymine Nucleotides; D014316:Tritium; D014498:Uracil; D006160:Guanosine Triphosphate; D000255:Adenosine Triphosphate; D004254:DNA Nucleotidyltransferases; D004229:Dithiothreitol