Fig. 2: Structure of DHFR and pmdhfr-ts variants. | Nature Communications

Fig. 2: Structure of DHFR and pmdhfr-ts variants.

From: Genome sequencing of Plasmodium malariae identifies continental segregation and mutations associated with reduced pyrimethamine susceptibility

Fig. 2

A The amino acid sequence of pmdhfr-ts (PmUG01_05034700) was obtained from PlasmoDB73 with domains annotated using Interpro domains (dihydrofolate reductase enzyme, DHFR: IPR001796; thymidylate synthase, TS: IPR000398). The number of nonsynonymous mutations (NS) found in each domain in the P. malariae database is annotated. B Amino acid sequences were aligned using Clustalo74 and visualised in Jalview75. Conserved amino acids between P. malariae and P. falciparum highlighted in grey, with mutations identified in P. malariae highlighted in blue and amino acid positions associated with pyrimethamine resistance in P. falciparum highlighted in red. C The crystal structure of PfDHFR-TS (with pyrimethamine bound, 3QGT) was downloaded from RCSB Protein Data Bank (grey) and the structure of PmDHFR-TS was predicted using I-TASSER76 (pink). Protein structures were aligned and visualised in UCSF Chimera77, highlighting the overlapping mutations around the pyrimethamine binding site, with the structure for pyrimethamine in black. P. malariae variant positions are annotated in green (49, 57, 58, 114) and P. falciparum variants associated with pyrimethamine resistance are annotated in red (51, 59, 108, 164).

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