biostudies-literatureSyroegin EANIH HHSNIGMS NIH HHS152-161https://www.ebi.ac.uk/biostudies/studies/S-EPMC9071271biostudies-literatureUnknown29(2)Ribosome-targeting antibiotics serve as powerful antimicrobials and as tools for studying the ribosome, the catalytic peptidyl transferase center (PTC) of which is targeted by many drugs. The classic PTC-acting antibiotic chloramphenicol (CHL) and the newest clinically significant linezolid (LZD) were considered indiscriminate inhibitors of protein synthesis that cause ribosome stalling at every codon of every gene being translated. However, recent discoveries have shown that CHL and LZD preferentially arrest translation when the ribosome needs to polymerize particular amino acid sequences. The molecular mechanisms that underlie the context-specific action of ribosome inhibitors are unknown. Here we present high-resolution structures of ribosomal complexes, with or without CHL, carrying spNature structural & molecular biologyStructural basis for the context-specific action of the classic peptidyl transferase inhibitor chloramphenicol.PMC9071271R01 GM132302P30 GM124165S10 OD021527Micura RFlemmich LVazquez-Laslop NSyroegin EAPolikanov YSKlepacki DfalseStructural basis for the context-specific action of the classic peptidyl transferase inhibitor chloramphenicol.Ribosome-targeting antibiotics serve as powerful antimicrobials and as tools for studying the ribosome, the catalytic peptidyl transferase center (PTC) of which is targeted by many drugs. The classic PTC-acting antibiotic chloramphenicol (CHL) and the newest clinically significant linezolid (LZD) were considered indiscriminate inhibitors of protein synthesis that cause ribosome stalling at every codon of every gene being translated. However, recent discoveries have shown that CHL and LZD preferentially arrest translation when the ribosome needs to polymerize particular amino acid sequences. The molecular mechanisms that underlie the context-specific action of ribosome inhibitors are unknown. Here we present high-resolution structures of ribosomal complexes, with or without CHL, carrying sp2022-01-01T00:00:00Z2022 Feb2025-04-04T08:01:38.928Z2025-04-04T08:01:38.928ZS-EPMC90712713516545510.1038/s41594-022-00720-y