Fig. 9: Identification of putative SC83288 protein targets by intact-cell ITDR-CETSA. | Nature Communications

Fig. 9: Identification of putative SC83288 protein targets by intact-cell ITDR-CETSA.

From: Mechanisms of PfDNMT2 inhibition and PfATP6-mediated resistance to the antimalarial candidate SC83288 in Plasmodium falciparum

Fig. 9: Identification of putative SC83288 protein targets by intact-cell ITDR-CETSA.The alt text for this image may have been generated using AI.

a Protein stabilization plot showing area under the curve (AUC) of thermal response profiles versus coefficient of determination (R²) for all detected proteins. Thermal response curves were generated at 50 °C, 55 °C, 60 °C, and a non-denaturing 37 °C control across increasing SC83288 concentrations and normalized to untreated samples. Red horizontal lines indicate ±2 times median absolute deviation (MAD) of AUC values; the dashed vertical line denotes R² > 0.8. Proteins exceeding both thresholds are numbered; stabilized and destabilized proteins are shown in red and blue, respectively. Experiments were performed on trophozoites treated with SC83288 (7.7 pM to 3.0 µM) for 1 h. b Alternative stabilization plot showing proteins with fold change ≥30% after thermal challenge plotted against R² > 0.8. Identified hists (see Supplementary Table 6 and Supplementary Data File 3): 1, BRCA2 protein, putative (PF3D7_1328200); 2, carbamoyl phosphate synthetase (PF3D7_1308200); 3, conserved membrane protein, unknown function (PF3D7_0505700); 4, conserved protein, unknown function (PF3D7_0811400); 5, AP-4 complex subunit ε, putative (PF3D7_0904100); 6, 40S ribosomal protein S17, putative (PF3D7_1242700); 7, cytochrome c oxidase copper chaperone, putative (PF3D7_1025600); 8, activator of Hsp90 ATPase, putative (PF3D7_0308500); 9, subtilisin-like protease 2 (PF3D7_1136900); 10, PHISTc exported protein, unknown function (PF3D7_0424000); 11, PHISTc exported protein, unknown function (PF3D7_1001800); 12, serine repeat antigen 5 (PF3D7_0207600); 13, cytochrome b5-like heme/steroid-binding protein, putative (PF3D7_0918100); 14, fumarate hydratase (PF3D7_0927300); 15, 1-Cys peroxiredoxin (PF3D7_0729200); 16, prolyl-4-hydroxylase α-subunit, putative (PF3D7_0829400); 17, cytosolic iron–sulfur protein assembly protein 1, putative (PF3D7_1209400); 18, isoleucine-tRNA ligase, putative (PF3D7_1225100); 19, casein kinase 2 α-subunit (PF3D7_1108400); 20, DNA replication licensing factor MCM2 (PF3D7_1417800); 21, kinetochore protein 7, putative (PF3D7_0410900); 22, conserved protein, unknown function (PF3D7_1133200); 23, S-adenosylhomocysteine hydrolase (PF3D7_0520900); 24, eukaryotic translation initiation factor 5, putative (PF3D7_1206700); 25, pseudouridylate synthase, putative (PF3D7_0914000); 26, glutaredoxin-like protein (PF3D7_0606900); 27, isocitrate dehydrogenase [NADP] (PF3D7_1345700); 28, tetratricopeptide repeat protein, putative (PF3D7_1310800). c Thermal response curves of the four highest-confidence hits. d Docking of SC83288 to the NAD-free (apo) structure of PfSAHH. Glide (green) and Vina (purple) poses are shown. The NAD binding pocket is highlighted in yellow. The Vina pose predicts an ionic interaction with E200 and backbone hydrogen bonds with V268, G344, and H398. Source data for (a–c) are provided as a Source Data file.

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