tRNA binding to programmed ribosomes increases the ribosomal affinity for tuberactinomycin O

Abstract

The binding of i4C-labelled tuberactinomycin 0 was analysed in equilibrium dialysis cells. The ionic conditions and the concentration of the labelled drug used in the binding assays allowed the binding of just one drug molecule per non-programmed ribosome. Under these conditions, the occupation of the ribosomal P-site by deacylated tRNAP" in the presence. of poly(U) increased the amount of [%]tuberactinomycin 0 bound by a factor of two. Kanamycin, gentamicin and neomycin reduced the binding of tuberactinomycin 0, whereas chloramphenicol, tetracycline, streptomycin and puromycin had no effect. A stimulation of the binding of tuberactinomycin 0 was found upon addition of erythromycin.

tRNAs as Antibiotic Targets

“…Tuberactinomycins (e.g., viomycin and capreomycin) are natural antibiotics that bind the interface of the 30S and 50S subunit of the ribosome and thereby inhibit translocation. These drugs have been used for the treatment of Mycobacterium tuberculosis infections including the multi-drug resistant types [ 152 , 153 , 154 ]. Thermorubins also bind at the interspace spanning the two ribosomal subunits and inhibits the binding of fMet-tRNA to the P-site [ 155 ].…”