Inhibitors of protein synthesis at the ribosome level. Studies on their site of action

Abstract

Previous studies have shown that 14C-labelled chloramphenicol binds to the 50 S subunit of 70 S ribosomes and this binding is prevented by a number of antibiotics included in the macrolide, streptogramin A, lincomycin and chloramphenicol groups (1). Erythromycin, the most studied of the macrolide antibiotics, also binds to bacterial ribosomes (2) and the binding site is located in the 50 S subunit (3). All these findings suggest that the inhibition of protein synthesis by these antibiotics results from their binding to the 50 S ribosomal subunit. By hybridization of subunits from resistant and sensitive ribosomes other workers have confirmed that the 50 S subunit is the site of action of lincomycin (4). Studies on the binding of aminoacyl-s-RNA to ribosomes also suggest that the site of action of antibiotics included in the chloramphenicol, macrolide, streptogramin A and lincomycin groups is on the 50 S ribosomal subunit whereas viridogrisein, streptogramin B and edeine act on the 30 S ribosomal subunit (5). However these studies do not show a direct evidence relating the binding of these antibiotics to ribosomes with their mode of action. In an attempt to show such a relationship the protein synthesizing activity of ribosomes or ribosomal subunits was studied after pretreatment with the inhibitors and removal of the unbound inhibitors by gel filtration; the results obtained are reported in this paper.