TY - JOUR T1 - Inhibition of Protein Synthesis by Polypeptide Antibiotics III. Ribosomal Site of Inhibition JF - Molecular Pharmacology JO - Mol Pharmacol SP - 444 LP - 453 VL - 2 IS - 5 AU - HERBERT L. ENNIS Y1 - 1966/09/01 UR - http://molpharm.aspetjournals.org/content/2/5/444.abstract N2 - The mechanism by which time antibiotics of the PA 114 complex inhibited protein synthesis in cell-free extracts of bacteria was studied. The antibiotic consists of at least two components belonging to two major groups, A and B. Although each antibiotic of groups A and B was effective individually in inhibiting protein synthesis in vivo, in combination they acted synergistically. PA 114 A inhibited protein synthesis best when messenger RNA was not attached to the ribosome and functioning. If the antibiotic was added after the messenger RNA-aminoacyl-tRNA-ribosome complex had formed and was functioning, inhibition of protein synthesis was decreased. This study showed that PA 114 A inimibited polyuridylic acid-directed binding of phenylalanyl-tRNA to 70 S ribosomes. The antibiotic inhibited ribosome function by specifically destroying the functioning of the 50 S ribosome subunit. PA 114 B acted synergistically to inhibit protein synthesis by enhancing the effect of the A component on the 50 S ribosome. These results suggested that the inhibition of protein synthesis by these antibiotics involved an interaction with a site on the 50 S ribosome subunit of the functional 70 S ribosome required for protein synthesis. This site was perhaps the same as or close to the site at which aminoacyl-tRNA bound. ACKNOWLEDGMENTS I wish to thank W. D. Celmer, Chas. Pfizer and Co., Inc., for the PA 114, PA 114 A, and PA 114 B; R. Donovick, Squibb Institute for Medical Research, for the vernamycin A and B α; F. J. Wolf, Merck, Sharp and Dohme, for the streptogramin; and Mrs. R. Tirey for her assistance in some of tue experiments. This investigation was supported by Public Health Service Grant GM-l2359-02 from the Division of General Medical Sciences, by Grant GB-3521 from the National Science Foundation, and by the American Lebanese Syrian Associated Charities (ALSAC). ER -