Fig. 6: Schematic diagram of the inhibition of eukaryotic IleRS by RM-A.
From: Inhibitory mechanism of reveromycin A at the tRNA binding site of a class I synthetase
RM-A occupies the binding site of the 3′ CCA end of tRNAIle on the catalytic domain of eukaryotic cytoplasmic IleRS. Thus, it blocks the productive binding of tRNAIle to the catalytic domain, while the alternative binding of tRNAIle to the editing domain of IleRS might not be affected. RM-A may also partially conflict with the phosphate groups of ATP. In contrast, the substrate l-isoleucine and the intermediate product Ile-AMP could co-bind with RM-A to the aminoacylation pocket of IleRS.
