Figure 2

Amino acid substitution profiles at six positions known to be critical for rocaglate binding. Six aa residues—158, 159, 163, 192, 195, 199—in the eIF4A RNA-binding pocket have been shown to be critical for rocaglate binding. Natural substitution tolerances at each of the six residues across the 365 eIF4A sequences analyzed here revealed four highly conserved positions—158, 159, 192, 195—and two variable positions—163 and 199. Of these, the latter shows a quasi bimodal frequency distribution (I or V), while the former shows a more promiscuous frequency distribution, with 14 different aa being tolerated in that position. The structure depicted above corresponds to the aa pattern TPFFQI; the rocaglate shown interacting with the eIF4A:RNA complex is silvestrol. The sequence logos were generated with Seq2Logo—2.0⁵⁰.