Studies on Transfer Ribonucleic Acid-Ribosome Complexes
Year: 1972
Type: article
Abstract: The effect of several antibiotics on peptidyl-puromycin synthesis by native polyribosomes was studied. As previously reported, sparsomycin was a competitive inhibitor of the reaction. The inhibition of transpeptidation by a single molecule of sparsomycin per ribosome monomer was consistent with a Hill plot of the kinetic data. In addition, for sparsomycin the Ki was equal to 1.6 x 10-7 m. Inhibition by althiomycin appeared to be noncompetitive. Chloramphenicol, amicetin, gougerotin, and blasticidin S showed both competitive and noncompetitive phases as inhibitors of transpeptidation. The two phases of inhibition by these antibiotics suggested that peptidyl-tRNA on the ribosome may exist in two distinct states with respect to reactivity with puromycin and the action of these antibiotics. These observations are interpreted in terms of models for ribosome function. Furthermore, it is clear from these studies that many antibiotics previously considered to be inhibitors of peptide bond synthesis do not inhibit peptidyl-puromycin formation on native polyribosomes. Thus, some antibiotics which are strong inhibitors of formylmethionly-, acetylphenylalanyl-, or polylysyl-puromycin synthesis produced little or no inhibition of peptidyl-puromycin synthesis on native polyribosomes. These antibiotics include macrolides (erythromycin, oleandomycin, niddamycin, carbomycin, tylosin, and spiramycin III), lincomycin, and streptogramins A (vernamycin A, PA114A). Since these antibiotics cannot inhibit peptide bond synthesis on polyribosomes, the mechanism of their inhibition of peptide bond synthesis with washed ribosomes and synthetic donors remains to be clarified; effects on such model systems for peptide bond synthesis cannot necessarily be extrapolated to their mode of action in intact cells.
Source: Journal of Biological Chemistry
Author: Sidney Pestka
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $3,430
OpenAlex ID: W1495652946