Table 1.
The T. brucei glycolytic enzymes as potential drug targets.
| Enzymea | PTS type | % identity to human counterpart | Status of therapeutic developmentb |
|---|---|---|---|
| TbHK1 | PTS2 [24] | 38% to HKDC1 | CV [7, 9], GV [7, 9], |
| 36% to HXK3 | |||
| TbHK2 | PTS2 [24] | GV [6, 7] | |
| PGI | PTS1 [25] | 57% to PGI isoform 2 | |
| PFK | PTS1 [25] | 27 % to PFK, platelet isoform | CV [26], GV [6] |
| ALD | PTS2 [26] | 49% to brain (C isozyme) | CV [27], GV [28] |
| TPI | I-PTS [29] | 54% to isoform 1 | GV [30] |
| GPDH | PTS1 [25, 31] | 38% to GPDH2 | |
| GAPDH | PTS1 [25] | 55% to spermatogenic GAPDH-2 | CV [32], GV [28] |
| PGK | |||
| PGKA | I-PTS [33] | 42% to PGK 1 | |
| PGKB | N/A | 43% to PGK 1 | |
| PGKC | PTS1 [25, 34] | 44% to PGK 1 | GV [35], CV [36] |
| PGM | N/A | 24% to CAMTA1 | GV [6] |
| ENO | N/A | 63% to ENO2 | GV [6] |
| PK | N/A | 50% to PKLR |
aFor enzyme abbreviations, see Figure 1. CAMTA1: calmodulin binding transcription activator 1; HKDC1: hexokinase domain containing protein 1; HXK3: hexokinase type 3; N/A: not applicable because the protein is cytosolic; PKLR: pyruvate kinase, liver, and RBC.
bStatus: CV: chemically validated target—inhibitors against the target are toxic to parasites; GV: genetically validated target—genetic manipulation of the enzyme leads to growth defects or cell death.