Fig. 5 Resistance-conferring mutations are localized near the BRD1389 binding site. a Close-up view of Pv cFRS (corn fl ower blue) with Hs cFRS (grey, PDB “ 3L4G [https://www.rcsb.org/structure/3l4g] ” ) as superimposed structures. Non-conserved residues within 5 Å of BRD1389 are shown. b Pv cFRS structure with known Pf cFRS mutations are highlighted in red. All resistance mutations map within the con fi nes of the active site region wherein the L550V mutant lies closest to the bound ligand. c , d Effect of L550V mutation on enzyme activity. Both enzymes show almost similar Km value for the ATP (18 ± 1 µ M for Pfc FRS wild type (WT) and 11 ± 1 µ M for Pfc fRS mutant (L550V)) whereas the Km value for L-Phe is increased ~10-fold for the mutant enzyme (0.25 ± 0.017 µ M for Pfc FRS (WT) and is 1.85 ± 0.84 µ M for Pfc FRS mutant (L550V)). Data are shown as mean ± SD ( n = 3 independent experiments). Source data are provided as a Source Data fi le.