Fig. 5: RM-A represents the first tRNA-site inhibitor of class I AARSs.
From: Inhibitory mechanism of reveromycin A at the tRNA binding site of a class I synthetase
a Structural superimposition of the catalytic domain of the E. coli LeuRS ∙ tRNALeu complex (wheat, PDB ID: 4AQ7) with that of the ScIleRS ∙ RM-A ∙ Ile-AMP complex (light blue) reveals that a large part of RM-A occupies the binding site of the tRNA 3’ CCA end. b Zoomed-in view of the conflicts between RM-A and the 3’ CCA end of tRNA. The residues that form polar interactions (indicated as black dashed lines) with the C1-10 and C20-24 side chains of RM-A in ScIleRS are shown in sticks, and the corresponding residues in E. coli LeuRS were found to form H-bonds (indicated as magenta dashed lines) with A74, C75 and A76 of tRNALeu. c, d ITC titrations of RM-A to ScIleRS premixed with in vitro transcribed tRNAIle (c) and with tRNAPro (d).
