MECHANISM OF INHIBITION OF PROTEIN SYNTHESIS BY FUSIDIC ACID AND RELATED STEROIDAL ANTIBIOTICS

Fusidic acid and related steroidal antibiotics were demonstrated to inhibit ribosomc-dependent GTPase activity of G factor in the presence and absence of sRNA, phenyl-alanyl-sRNA and/or poly U. They also inhibited polypeptide synthesis, and the grade of inhibition of both reactions was parallel. The inhibition of polypeptide synthesis by fusidic acid was reversed by excess of G factor, but not by excess of T factor or ribo-somes, Puromycin-dependent release of peptide from the ribosomes was not significantly affected by fusidic acid in the absence of GTP and G factor; but the puromycin reaction, enhanced by GTP and G factor, was inhibited by the antibiotic. The results indicate that fusidic acid and related antibiotics affect polypeptide synthesis by inhibiting GTPase activity of G factor and by inhibiting translocation of peptidyl-sRNA on the ribosomes. The results also seem to support the assumption that GTP split reaction, linked to the ribosomes and G factor, is essential for translocation of peptidyl-sRNA on the ribosomes. The ribosome-associated GTPase activity of G factor was not significantly affected by blasticidin S, mikamycin B, bottromycin A2, chloramphenicol, thiophenicol, and erythromycin. © 1969 BY THE JOURNAL OF BIOCHEMISTRY.