THE RIBOSOMAL PEPTIDYL TRANSFERASE CENTER. POSSIBLE BASES FOR THE COMMON ACTION OF PEPTIDE BOND FORMATION INHIBITORS OF BACTERIAL AND EUKARYOTIC RIBOSOMES

Abstract

Mainly protein L16 and to a lesser extent L2, L15, L27 of the bacterial ribosome and proteins L21/23, L26, L27, L28, L29 and L36 of rat liver ribosomes have been postulated as being involved in the ribosomal peptidyl transferase center. However no single protein has been found individually responsible from this activity and when bacterial ribosomes are treated with proteinase K, all these proteins that might be involved in peptidyl transferase activity are lost at faster rate than the activity itself. Furthermore other studies suggest that there is no identity between any of the individual proteins of the bacterial and eukaryotic ribosomes that were postulated as being involved in the peptidyl transferase activity, although there are a number of antibiotics (sparsomycin, blasticidin S, gougerotin, amicetin and anthelmycin) which are equally active in blocking peptidyl transferase activity by bacterial and eukaryotic ribosomes. Furthermore the treatment with a number of chemical reagents that modify the proteins have very little or no effect on the peptidyl transferase of the bacterial ribosome. On the other hand there is increasing evidence supporting the relevant role of the ribosomal RNA in the peptidyl transferase center. Thus the replacement of Mg2+ by Ba++ induces the breakage of the ribosomal RNA with a concomitant decrease in the peptidyl transferase activity. Furthermore ribosome treatment with a number of reagents that chemically modify the ribosomal RNA also affect drastically the peptidyl transferase activity. Therefore we propose that antibiotics which specifically inhibit peptide bond formation by bacterial and eukaryotic ribosomes (sparsomycin, gougerotin, blastîcîdin S, amicetin and anthelmycin) might recognize some moiety common in the RNA of the larger ribosomal subunit.