Table 3.
Conservation level of the protein sites constituting the K13 KREP shallow pocket.
| AAa position | Ref. AAa (P. fal) | PfK13 mutantb | Sequence variation across Apicomplexa species |
λ-based KREP rank n, (%)c |
|
|---|---|---|---|---|---|
| Plasmodium (n = 21) | Non-Plasmodium (n = 22) | ||||
| 451 | F | — | F (21) | H (16); C (4); T (2); S(1); N (1) | 132 (46.48) |
| 456 | Y | — | Y (21) | H (12); I (7); P (2); Y (1) | 125 (44.01) |
| 482 | Y | SAFR | Y (21) | Y (17); H (5) | 37 (13.03) |
| 498 | N | IAFR | N (21) | Q (13); Y (7); H (2) | 44 (15.49) |
| 529 | R | K AFR | R (21) | R (22) | 1 (0.35) |
| 530 | N | K AFR /Y AFR | N (21) | N (22) | 9 (3.17) |
| 546 | Y | — | Y (21) | F (22) | 13 (4.58) |
| 551 | I | — | I (21) | I (19); V (3) | 86 (30.28) |
| 576 | S | L AFR | S (21) | S (22) | 3 (1.06) |
| 577 | S | P AFR | S (21) | S (22) | 10 (3.52) |
| 593 | T | S AFR | T (15); A (6) | T (22) | 19 (6.69) |
| 597 | R | — | R (21) | R (22) | 12 (4.23) |
| 623 | S | C SEA | S (21) | S (22) | 2 (0.70) |
| 624 | S | — | S (21) | A (15); G (7) | 23 (8.10) |
| 640 | I | VAFR | I (21) | I (19); M (2); V(1) | 42 (14.79) |
| 671 | M | — | M (21) | M (17); L (3); I (1); F (1) | 73 (25.70) |
| 672 | N | — | N (21) | D (22) | 47 (16.55) |
| 688 | E | — | E (21) | Q (22) | 45 (15.85) |
| 717 | F | — | F (21) | Y (19); S (3) | 33 (11.62) |
aAA: amino acid position. Ref. AA indicates the wild type amino acid in PfK13. bNone of the PfK13 mutant positions located at the K13 KREP shallow pocket was reported to confer the ART-R phenotype. All PfK13 mutants presented here have been described in one or two parasite samples from large population surveys5,8,9,91,92. AFR (Africa) and SEA (Southeast Asia) refer to the geographic origin of the PfK13 mutant parasite isolate. cThe rank attributed to the shallow pocket positions was based on the site-specific substitution rates λ (Supplementary Dataset S1) estimated for the 284 studied KREP positions using FuncPatch33. The lower the rank, the more conserved was the position. Positions in bold are those belonging to the 10% most conserved positions of KREP.