Competition between trichodermin and several other sesquiterpene antibiotics for binding to their receptor site(s) on eukaryotic ribosomes

Abstract

Of the 5 sesquiterpene antibiotics tested and found to inhibit protein synthesis in yeast [Saccharomyces cerevisiae] spheroplasts, trichothecin, trichodermol or trichodermin stabilized polyribosomes whereas, in contrast, verrucarin A or T-2 toxin induced run off of polyribosomes with a corresponding increase in 80S monoribosomes. The effect of fusarenon X on the system could not be determined as the drug failed to enter the cells. [acetyl-14C]Trichodermin bound to yeast polyribosomes with a Kd of 2.10 .mu.M and to yeast run off ribosomes with a Kd of 0.72 .mu.M. Trichothecin, trichodermol, fusarenon X, T-2 toxin and verrucarin A competed with [acetyl-14C]trichodermin for binding to its receptor site on run off ribosomes. The observed competition was quantitatively similar for all the drugs tested. The 5 drugs competed to different extents with trichodermin for binding to its receptor site on polyribosomes. Trichothecin competed with relative efficiency, whereas verrucarin A competed poorly and the other drugs occupied intermediate positions between these 2 extremes. Studies were also carried out with yeast run off ribosomes prepared from both a wild-type strain and a strain resistant to trichodermin. Competition experiments between verrucarin A and [3H]anisomycin indicated that verrucarin A bound to run off ribosomes from the mutant strain less efficiently than to those from the wild-type.