Inhibition of eukaryotic ribonuclease P activity by aminoglycosides: kinetic studies

The effect of several aminoglycoside antibiotics on ribonuclease P (RNase P ) mas investigated using an in vitro experimental system from Dictyostelium discoideum. Detailed kinetic analysis showed that all aminoglycosides test ed (tobramycin, gentamicin, kanamycin, paromomycin, neomycin) behave as cla ssical non-competitive inhibitors, with neomycin being the strongest inhibi tor. The inhibition effect is attributed to the electrostatic competition o f the cationic aminoglycosides with magnesium ions required for catalysis, Increasing Mg2+ ion concentrations reduced the effect of aminoglycosides on RNase P activity. Detailed kinetic analysis showed that aminoglycosides co mpete with Mg2+ for common binding sites on RNase P holoenzyme. (C) 2000 Fe deration of European Biochemical Societies. Published by Elsevier Science B .V. All rights reserved.