Inhibition by Fusidic Acid of Transferase II in Reticnlocyte Protein Synthesis

Abstract

Protein synthesis with endogenous mRNA and polyphenylalanine synthesis with poly U were inhibited by fusidic acid in a highly fractionated reticulocyte system. It interfered with ribosome-dependent GTPase activity of TF-II. The grade of inhibition by fusidic acid of the polypeptide synthesis and the GTPase reaction was parallel and it was comparable to what was observed in the bacterial system. The antibiotic did not significantly affect the puromycin reaction with polyphenylalanyl-tRNA or acetylphenylalanyl-tRNA, presumably attached to the donor site of ribosomes. However, puromycin reaction, enhanced by GTP and TF-II, was inhibited by fusidic acid. It suggested that the antibiotic selectively inhibited the translocation of peptidyl-tRNA from the acceptor site to the donor site on the reticulocyte ribosomes. The results were in accordance with those obtained with bacterial G factor, and indicated that TF-II may be a mammalian equivalent of G factor.