Practice question

Chloramphenicol binds domain V central loop of 23S rRNA in 50S subunit peptidyl transferase center overlapping A-site tRNA 3' end. Crystallography shows contacts with A2451, A2452, U2506 critical for aminoacyl positioning. Binding prevents proper orientation of incoming aminoacyl-tRNA inhibiting peptide bond formation arresting elongation. Low concentrations bacteriostatic, higher bactericidal. Mitochondrial ribosomes sensitive due to bacterial ancestry causing toxicity. Resistance conferred by cat gene encoding chloramphenicol acetyltransferase acetylating drug reducing ribosome affinity. Mechanism distinct from aminoglycosides affecting decoding or tetracyclines blocking A-site entry, exemplifying peptidyl transferase targeted inhibition selectively action on bacterial translation machinery effectively exploited therapeutically despite resistance concerns.