Table 2.
Suggested antimalarial drug target genes and possibility of evolutionary conservation of yeast synthetic lethal genes.
| Plasmodium | Plasmodium | Saccharomyces cerevisiae |
|---|---|---|
| ADR gene | ADR gene’s inferred SL partner | Similarities to Protein Data Bank Chains (ADR gene’s inferred SL partner) |
| PB000415.02.0 (ADR gene: PfDHFR-TS)/bifunctional dihydrofolate reductase-thymidylate synthase, putative | PB000779.01.0 (PB000415.02.0’s neighbor gene)/Snf2-related CBP activator, putative | Chromo domain-containing protein 1 (% of PlasmoDB protein Covered: 42;% Identity: 32; P-value: 2.5 × 10−78) |
| PFD0830w (ADR gene: PfDHFR-TS)/bifunctional dihydrofolate reductase-thymidylate synthase | PF08_0048 (PFD0830w’s neighbor gene)/Snf2-related CBP activator, putative | Chromo domain-containing protein 1 (% of PlasmoDB protein Covered: 34;% Identity: 33; P-value: 1.5 × 10−75) |
| PF13_0019 (ADR gene: PfNHE1)/sodium/hydrogen exchanger, Na, H antiporter | MAL13P1.170 (PF13_0019’s neighbor gene)/nucleotidyltransferase, putative | Poly(A) RNA polymerase protein 2 (% of PlasmoDB protein Covered: 32; % Identity: 31; P-value: 5.2 × 10−29) |
| PVX_089950 (ADR gene: PfDHFR-TS)/bifunctional dihydrofolate reductase-thymidylate synthase 1, putative | PVX_089365 (PVX_089950’s neighbor gene)/helicase, putative | Chromo domain-containing protein 1 (% of PlasmoDB protein Covered: 32,% Identity: 35; P-value: 3.5 × 10−75) |
| PVX_118100 (ADR gene: PfMDR2)/multidrug resistance protein 2, putative | PVX_099360 (PVX_118100’s neighbor gene)/gamma-glutamylcysteine synthetase, putative | Glutamate–cysteine ligase (% of PlasmoDB protein Covered: 63;% Identity: 32; P-value: 7.6 × 10−64) |
The list of selected SL gene pairs is shown in this table. Potential antimalarial drug targets (inferred SL partners for ADR genes) are suggested for future experimental validation. All SL genes represented in this table do not have any human homologous gene. For application to yeast drugs provided by the FitDB, we conjectured the possibility of evolutionary conservation between the yeast genes and Plasmodium homologs by identifying similarities in protein chains in the Protein Data Bank. The five drug target genes are also shown in Fig. 5.