Supplementary Materials

The PDF file includes:

  • Materials and Methods
  • Fig. S1. Coaggregation of protein complexes in P. falciparum melt curve CETSA.
  • Fig. S2. The comparison of protein melting behavior between RBC, P. falciparum, and K562 cells.
  • Fig. S3. The effect of pyrimethamine on thermal stability of PfDHFR-TS across four CETSA experimental variants.
  • Fig. S4. Mefloquine-induced stabilization profiles of Mge1 and Hsp70-3 in intact-cell ITDR assay.
  • Fig. S5. Western blot detection of PfPNP stabilization in mefloquine- and quinine-treated ITDR datasets.
  • Fig. S6. Human protein engagement by antimalarial drugs in intact-cell ITDR assays.
  • Fig. S7. ITC analysis of quinine and mefloquine binding to PfPNP.
  • Fig. S8. Cocrystal structure overlay with 2bsx and 1nw4 reference PfPNP structures.
  • Table S1. High- and low-confidence protein stabilizations observed in quinine/mefloquine ITDR assays.
  • Table S2. SPR measurements of PfPNP-mefloquine/quinine/ImmH KD.
  • Table S3. ITC binding affinities for PfPNP-mefloquine/quinine interaction.
  • Table S4. PfPNP in vitro enzymatic activity inhibition by mefloquine and quinine.
  • Table S5. Combinatory effect of fixed-ratio drug combinations against P. falciparum 3D7 strain.
  • Table S6. Data collection and refinement statistics of PfPNP-mefloquine and PfPNP-quinine cocrystals.
  • Legends for data S1 to S10
  • References (7381)

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Other Supplementary Material for this manuscript includes the following:

  • Data S1 (.pdf format). Intact-cell and lysate CETSA melt curve analysis of P. falciparum proteome.
  • Data S2 (.pdf format). Intact-cell CETSA melt curve analysis of RBC proteome.
  • Data S3 (.pdf format). PM lysate ITDR–plasmodium proteome.
  • Data S4 (.pdf format). E64d intact-cell ITDR–plasmodium proteome.
  • Data S5 (.pdf format). Quinine lysate ITDR–plasmodium proteome.
  • Data S6 (.pdf format). Mefloquine lysate ITDR–plasmodium proteome.
  • Data S7 (.pdf format). Quinine intact-cell ITDR–plasmodium proteome.
  • Data S8 (.pdf format). Quinine intact-cell ITDR–human proteome.
  • Data S9 (.pdf format). Mefloquine intact-cell ITDR–plasmodium proteome.
  • Data S10 (.pdf format). Mefloquine intact-cell ITDR–human proteome.