title: Allosteric inhibition by aphidicolin of the activity of DNA polymerase alpha from mouse myeloma.
abstract: The mechanism of inhibition by aphidicolin of the activity of purified DNA polymerase alpha was studied. In the presence of aphidicolin and activated DNA, DNA polymerase alpha from mouse myeloma did not show Michaelis kinetics with respect to changes in nucleotide substrate concentration (i.e., dGTP & dTTP). A plot of the reaction velocity versus dGTP or dTTP concentration was hyperbolic with an intermediary plateau. The double reciprocal plot was concave downwards, and the Hill plot gave Hill coefficients of less than 1.0 over most of the curve. These results indicate that aphidicolin acts as an allosteric inhibitor for DNA polymerase alpha and that DNA polymerase alpha functions as a multisite enzyme that exhibits negative cooperativity among at least 3 binding sites of the nucleotide substrates (dGTP & dTTP).
mesh_terms: D000818:Animals; D016590:Aphidicolin; D002460:Cell Line; D004257:DNA Polymerase II / Q000037:antagonists & inhibitors*; D004224:Diterpenes / Q000494:pharmacology*; D007700:Kinetics; D051379:Mice; D009374:Neoplasms, Experimental / Q000201:enzymology; D019384:Nucleic Acid Synthesis Inhibitors; D010954:Plasmacytoma / Q000201:enzymology*
chemical_list: D004224:Diterpenes; D019384:Nucleic Acid Synthesis Inhibitors; D016590:Aphidicolin; D004257:DNA Polymerase II