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. 2017 Feb 8;13(2):e1006172. doi: 10.1371/journal.ppat.1006172

Fig 6. Circumvention of the PfFNT G107S resistance mutation and binding mode.

Fig 6

(A) l-lactate uptake via PfFNT G107 S/A/C/V mutants over time and derived transport rates (B). (C) Relative selectivity of MMV007839, BH-296, and the pharmacophore for the PfFNT G107S resistance mutation. A ratio of 1 would indicate equal efficiency on wildtype and mutant PfFNT. (D) Efficiency of BH-296 on PfFNT G107S in yeast (black) and resistant parasites (red); dashed lines indicate efficiency on wildtype PfFNT and parasites for comparison. (E) Efficiency of the pharmacophore on PfFNT G107S in yeast compared to PfFNT wildtype (dashed line). The error bars indicate S.E.M. (n ≥ 3). (F) Proposed model of MMV007839 binding to PfFNT and (G) strategy to circumvent the clash with G107S by introducing limited flexibility into the inhibitor scaffold.