Antibiotic inhibition of the movement of tRNA substrates through a peptidyl transferase cavity

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Abstract
The present review attempts to deal with movement of tRNA substrates through the peptidyl transferase centre on the large ribosomal subunit and to explain how this movement is interrupted by antibiotics. It builds on the concept of hybrid tRNA states forming on ribosomes and on the observed movement of the 5′ end of P-site-bound tRNA relative to the ribosome that occurs on peptide bond formation. The 3′ ends of the tRNAs enter, and move through, a catalytic cavity where antibiotics are considered to act by at least three primary mechanisms: (i) they interfere with the entry of the aminoacyl moiety into the catalytic cavity before peptide bond formation; (ii) they inhibit movement of the nascent peptide along the peptide channel, a process that may generally involve destabilization of the peptidyl tRNA, and (iii) they prevent movement of the newly deacylated tRNA between the P/P and hybrid P/E sites on peptide bond formation.Key words: peptidyl transferase cavity, transient tRNA states, antibiotics, inhibitory mechanism, subunit–subunit interactions.