title: Inhibition of eukaryotic ribonuclease P activity by aminoglycosides: kinetic studies.
abstract: The effect of several aminoglycoside antibiotics on ribonuclease P (RNase P) was investigated using an in vitro experimental system from Dictyostelium discoideum. Detailed kinetic analysis showed that all aminoglycosides tested (tobramycin, gentamicin, kanamycin, paromomycin, neomycin) behave as classical non-competitive inhibitors, with neomycin being the strongest inhibitor. The inhibition effect is attributed to the electrostatic competition of the cationic aminoglycosides with magnesium ions required for catalysis. Increasing Mg(2+) ion concentrations reduced the effect of aminoglycosides on RNase P activity. Detailed kinetic analysis showed that aminoglycosides compete with Mg(2+) for common binding sites on RNase P holoenzyme.
authors.affiliation: Department of Biochemistry, School of Medicine, University of Patras, 26500 Patras, Greece.
authors.forename: A
authors.initials: A
authors.lastname: Tekos
authors.forename: A
authors.initials: A
authors.lastname: Tsagla
authors.forename: C
authors.initials: C
authors.lastname: Stathopoulos
authors.forename: D
authors.initials: D
authors.lastname: Drainas
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001667:Binding, Competitive; D002412:Cations; D004023:Dictyostelium / Q000201:enzymology*; D004722:Endoribonucleases / Q000037:antagonists & inhibitors*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005839:Gentamicins / Q000494:pharmacology; D007612:Kanamycin / Q000494:pharmacology; D007700:Kinetics; D008274:Magnesium / Q000494:pharmacology; D008433:Mathematics; D009355:Neomycin / Q000494:pharmacology; D010303:Paromomycin / Q000494:pharmacology; D016337:RNA, Catalytic / Q000037:antagonists & inhibitors*; D043262:Ribonuclease P; D055672:Static Electricity; D014031:Tobramycin / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D002412:Cations; D004791:Enzyme Inhibitors; D005839:Gentamicins; D016337:RNA, Catalytic; D007612:Kanamycin; D010303:Paromomycin; D004722:Endoribonucleases; D043262:Ribonuclease P; D009355:Neomycin; D008274:Magnesium; D014031:Tobramycin