Table 1 |
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Heterologous expression of 32 potential antimalarial drug targets. |
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|
PlasmoDB annotation |
Product |
Drug-ability Index (max is 1) |
MM (Da) |
pI |
Heterologous Expression (Ref) |
Tag |
Special conditions (e.g. codon adaptation, TM, trunctions) |
Structure (PDB code) |
|
|
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|
PF14_0053 |
Ribonucleotide reductase small subunit |
1 |
40600 |
5.2 |
E. coli [212] |
His and GST |
- |
- |
|
PFD0830w |
Bifunctional dihydrofolate reductase-thymidylate synthase |
1 |
71738 |
7.2 |
- E. coli (various) - S. cerevisiae (complemeted) (various) - Cell free systems [207] |
- |
- Purposely truncated versions or domains - Codon optimised - S. cerevisiae adapted |
|
|
PFE0520c |
Topoisomerase I |
1 |
98110 |
9.8 |
- |
- |
- |
- |
|
PFF0160c |
Dihydroorotate dehydrogenase, mitochondrial precursor |
1 |
65559 |
9.4 |
E. coli [213] |
His |
N-terminally truncated pRIL tRNA additions |
|
|
PFI1020c |
Inosine-5'-monophosphate dehydrogenase |
1 |
56151 |
8.0 |
- |
- |
- |
- |
|
PF11_0377 |
Casein kinase 1 |
0.9 |
37631 |
9.7 |
E. coli [214] |
His |
||
|
PF14_0192 |
Glutathione reductase |
0.9 |
56679 |
8.1 |
E. coli complementation [215] |
His |
Gene complementation |
|
|
PFI1685w |
cAMP-dependent protein kinase catalytic subunit |
0.9 |
40197 |
9.1 |
- |
- |
- |
- |
|
PFI1170c |
Thioredoxin reductase |
0.9 |
59687 |
7.8 |
E. coli [216] |
His |
- |
- |
|
MAL13P1.279 |
Protein kinase 5 |
0.9 |
32997 |
8.0 |
E. coli [217] |
His |
pRIL tRNA addition |
|
|
PFC0525c |
Glycogen synthase kinase 3 |
0.9 |
51616 |
5.2 |
E. coli [218] |
V5/His-/thioredoxin |
- |
- |
|
PFL2250c |
Rac-beta serine/threonine kinase |
0.9 |
88096 |
10 |
E. coli [219] |
His or GST |
pRIL tRNA addition |
- |
|
PF10_0121 |
Hypoxanthine phosphoribosyltransferase |
0.8 |
70076 |
4.6 |
E. coli [220] |
- |
- |
|
|
PF10_0165 |
DNA polymerase delta catalytic subunit |
0.8 |
127072 |
8.7 |
E. coli [221] |
3-galactosidase |
- |
- |
|
PF10_0322 |
S-adenosylmethionine decarboxylase-ornithine decarboxylase |
0.8 |
168171 |
6.3 |
E. coli [222] |
STREP |
- |
- |
|
PF13_0141 |
L-lactate dehydrogenase |
0.8 |
34108 |
7.6 |
- |
- 1 TM/1 signal peptide - 2xYT - reducing cell growth temperature to 15°C |
||
|
PF13_0287 |
Adenylosuccinate synthetase |
0.8 |
50066 |
7.7 |
E. coli [225] |
- |
Low-temperature inductions were carried out at 20°C for 12 h |
|
|
PFI1090w |
S-adenosylmethionine synthetase |
0.8 |
44844 |
6.7 |
E. coli [226] |
His |
- |
|
|
PF14_0076 |
Plasmepsin 1 precursor |
0.8 |
51461 |
7.2 |
1 TM |
|||
|
PF14_0077 |
Plasmepsin 2 precursor |
0.8 |
51481 |
5.3 |
E. coli [227] |
- 1 TM - Solubilised and refolded |
||
|
PF14_0125 |
Deoxyhypusine synthase |
0.8 |
57429 |
6 |
P. vivax expressed |
1 TM |
- |
|
|
PF14_0127 |
N-myristoyltransferase |
0.8 |
47971 |
8.3 |
E. coli [228] |
His |
- |
-. |
|
PF07_0029 |
Heat shock protein 86 |
0.8 |
86167 |
4.7 |
E. coli [229] |
His |
- |
- |
|
PF14_0164 |
NADP-specific glutamate dehydrogenase |
0.8 |
52547 |
7.3 |
- |
- |
||
|
PF14_0378 |
Triose-phosphate isomerase |
0.8 |
27935 |
6.4 |
E. coli [232] |
- |
- |
|
|
PFD0590c |
DNA polymerase alpha |
0.8 |
225404 |
8.4 |
- |
- |
- |
- |
|
PFE1050w |
Adenosylhomocysteinase(S-adenosyl-L-homocystein e hydrolase) |
0.8 |
52840 |
5.7 |
- |
- |
||
|
PFF0730c |
Enoyl-acyl carrier reductase |
0.8 |
49763 |
9.5 |
E. coli [235] |
MBP |
pRIL tRNA additions |
|
|
PFI1260c |
Histone deacetylase |
0.8 |
51376 |
6.3 |
Cell free systems [236] |
No |
- |
- |
|
PFI1105w |
Phosphoglycerate kinase |
0.8 |
45427 |
8.1 |
E. coli [237] |
His |
- |
|
|
PFD1050w |
Alpha-tubulin II |
0.8 |
49878 |
4.6 |
- |
- |
- |
- |
|
PFD0420c |
Flap exonuclease 1 |
0.8 |
76868 |
8.1 |
- |
- |
- |
- |
|
|
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|
The TDR Targets database (tdrtargets.org) were searched for P. falciparum genes with a druggability evidence index ≥0.7. Hypothetical or putative proteins were excluded. |
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|
Birkholtz et al. Malaria Journal 2008 7:197 doi:10.1186/1475-2875-7-197 |
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