Hygromycin A, a novel inhibitor of ribosomal peptidyltransferase.
In cell-free systems from Escherichia coli, hygromycin A inhibits polypeptide synthesis directed by either poly(U) or phage R 17 RNA, and the reaction of puromycin with either natural peptidyl-tRNA, or AcPhe-tRNA, or the 3'-terminal fragment of AcLeu-tRNA (C-A-C-C-A-LeuAc). In contrast, the antibiotic does no inhibit the enzymatic binding of Phe-tRNA to ribosomes or the translocation of AcPhe-tRNA. It is concluded that hygromycin A is a specific inhibitor of the peptide bond formation step of protein synthesis. The action of hygromycin A on peptidyl transfer is similar to that of chloramphenicol, an antibiotic that shares some common structural features with hygromycin A. Both antibiotics inhibit the binding of C-A-C-C-A-Leu to the acceptor site of peptidyl transferase and stimulate that of C-A-C-C-A-LeuAc to the donor site of the enzyme. Moreover, hygromycin A blocks the binding of chloramphenicol to ribosomes, indicating that the binding sites of the antibiotics may be closely related. Hygromycin A is a more potent agent than chloramphenicol and binds quite strongly to ribosomes.
D000217:Acyltransferases / Q000037:antagonists & inhibitors*; D000617:Aminoglycosides / Q000378:metabolism / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000494:pharmacology*; D001667:Binding, Competitive / Q000187:drug effects; D002701:Chloramphenicol / Q000494:pharmacology; D002934:Cinnamates; D004917:Erythromycin / Q000494:pharmacology; D004926:Escherichia coli / Q000201:enzymology*; D006921:Hygromycin B / Q000031:analogs & derivatives*; D008034:Lincomycin / Q000494:pharmacology; D010441:Peptide Chain Elongation, Translational / Q000187:drug effects; D010458:Peptidyl Transferases / Q000032:analysis / Q000037:antagonists & inhibitors*; D011132:Polyribosomes / Q000201:enzymology; D012313:RNA / Q000378:metabolism; D012270:Ribosomes / Q000201:enzymology* / Q000378:metabolism
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D002934:Cinnamates; D006921:Hygromycin B; C026273:hygromycin A; D012313:RNA; D004917:Erythromycin; D002701:Chloramphenicol; D008034:Lincomycin; D000217:Acyltransferases; D010458:Peptidyl Transferases