Hygromycin A, a Novel Inhibitor of Ribosomal Peptidyltransferase

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Abstract
In cell‐free systems from Escherichia coli, hygromycin A inhibits polypeptide synthesis directed by either poly(U) or phage R17 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 not 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.