Open AccessMechanism of Action of Aminoglycoside Antibiotics
Author(s) -
GOFFIC François,
CAPMAU MarieLouise,
TANGY Frédéric,
BAILLARGE Michèle
Publication year - 1979
Publication title -
european journal of biochemistry
Language(s) - English
Resource type - Journals
eISSN - 1432-1033
pISSN - 0014-2956
DOI - 10.1111/j.1432-1033.1979.tb06264.x
Subject(s) - tobramycin , aminoglycoside , ribosome , mechanism (biology) , mechanism of action , antibiotics , chemistry , derivative (finance) , microbiology and biotechnology , biochemistry , biology , rna , gentamicin , physics , in vitro , quantum mechanics , financial economics , economics , gene
6′‐ N ‐[ 14 C]Acetyl‐tobramycin and [ 3 H]tobramycin were synthesized and their binding to Escherichia coli ribosomes and ribosomal subunits studied using equilibrium dialysis. The 70‐S ribosome, as well as its 50‐S and 30‐S subunits, bound tightly to 6′‐ N ‐acetyl‐tobramycin. The binding of [ 3 H]tobramycin to ribosomes was quite different. The 70‐S ribosome was observed to possess several classes of binding sites; of these, one was determined to be of higher affinity and lower capacity, the 6′‐ N ‐[ 14 C]acetyl‐tobramycin site. The isotopic dilution method was used to define the specificity of the interaction. The selective binding of 6′‐ N ‐[ 14 C]acetyl‐tobramycin was highly reversible by tobramycin, kanamycins A, B, C and neomycin, but not by streptomycin or erythromycin. Gentamicin C 1a was a poor inhibitor. This suggested that either the kanosamin or garosamin rings might be determinant in the binding of these molecules, as well as the 6′‐amino group.