[Kinetics of the interaction of methylene diphosphonic acid and inorganic pyrophosphate with DNA-dependent RNA-polymerase from calf thymus].
The kinetics of interaction of PPi and its diphosphonic analog, methylenediphosphonic acid (MDPA), with nucleoside triphosphates, DNA and Mg2+ binding sites of DNA-dependent RNA polymerase II from calf thymus was investigated. The values of apparent Km in the NTP polymerization reaction for ATP and CTP equal to 2.7 X 10(-4) and 1.8 X 10(-4) M, respectively, were determined. It was shown that MDPA and PPi competitively inhibited the RNA polymerase reaction with respect to nucleoside triphosphate. The inhibition constants (Ki) of ATP and CTP incorporation for MDPA were 2.2 X 10(-4) and 3.3 X 10(-4) M, respectively, while those of the nucleoside triphosphate incorporation for PPi were equal to 1.4 X 10(-4) and 2.0 X 10(-4) M, respectively. MDPA and PPi were incompetitive inhibitors of template (DNA) and Mn2+. A possible mechanism of inhibition of the RNA polymerase reaction by MDPA is proposed.
Fomovskaia
G N
GN
Komissarenko
S V
SV
D000818:Animals; D001667:Binding, Competitive; D002417:Cattle; D011756:Diphosphates / Q000494:pharmacology*; D004164:Diphosphonates / Q000494:pharmacology*; D066298:In Vitro Techniques; D007700:Kinetics; D012319:RNA Polymerase II / Q000037:antagonists & inhibitors*; D013379:Substrate Specificity; D013950:Thymus Gland / Q000201:enzymology
D011756:Diphosphates; D004164:Diphosphonates; C027474:methylene diphosphonate; D012319:RNA Polymerase II
Kinetika vzaimodeĭstviia metilendifosfonovoĭ kisloty i neorganicheskogo pirofosfata s DNK-zavisimoĭ RNK-polimerazoĭ II timusa telenka.