Peptidyltransferase Inhibition by Trichodermin

Abstract

Abstract The sesquiterpenoid antibiotics, trichodermin and T-2 toxin, are inhibitors of polyphenylalanine biosynthesis and peptide chain termination in vitro with rabbit reticulocyte extracts. The formation of fMet-puromycin from fMet-tRNA· AUG·ribosome complexes, an activity associated with the 60 S ribosomal peptidyltransferase, is inhibited effectively by these antibiotics. Release factor (RF)-dependent release of formylmethionine from these ribosomal complexes is also prevented under conditions where GTP and codon recognition are not required. Both the RF-dependent hydrolysis of ribosome-bound fMet-tRNA and the synthesis of fMet-puromycin require an active peptidyltransferase and it appears likely, therefore, that trichodermin and T-2 toxin affect this ribosomal activity involved in protein biosynthesis. A number of other partial reactions examining intermediate steps of peptide chain elongation and termination are not affected by these antibiotics.