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Table 3 Gold standard set of essential enzymes

From: Antimalarial drug targets in Plasmodium falciparum predicted by stage-specific metabolic network analysis

EC Reaction Choke-points Found by FBA Comment Reference
1.1.1.205 IMP dehydrogenase Yes No Precursor import (adenosine, hypoxanthine, inosine) [133]
1.1.1.267 1-deoxy-D-xylulose-5-phosphate reducetoisomerase Yes Yes   [84]
1.3.1.9 enoyl-ACP-reductase Yes Yes   [134136]
1.3.3.1 Dihydroorotate oxidase No Yes   [9295, 137]
1.3.99.1 Succinate dehydrogenase No No Presumably unspecific off-target effects [75]
1.5.1.3 Dihydrofolate reductase No No Necessary to block all reactions catalyzed by the enzyme [138140]
1.6.5.3 NADH dehydrogenase (ubiquinone) No No Presumably unspecific off-target effects [74]
1.8.1.7 glutathione reductase Yes Yes   [141, 142]
1.8.1.9 thioredoxin reductase Yes Yes   [143, 144]
1.10.2.2 cytochrome c reductase Yes Yes   [145]
1.15.1.1 superoxide dismutase Yes Yes   [146]
1.17.4.1 Ribonucleoside-diphosphate reductase No Yes   [147149]
2.1.1.100 Protein-S-isoprenylcysteine-O-methyltransferase Yes Yes   [150, 151]
2.1.1.103 Phosphoethanolamine methyltrans-ferase Yes No Presumably unspecific off-target effects [77, 79]
2.1.1.45 Thymidylate synthase No Yes   [152, 153]
2.1.1.64 3-Demethylubiquinone-9,3-O-methyltransferase Yes Yes   [154]
2.3.1.24 sphingosine-N-acyltransferase Yes Yes   [155]
2.3.1.37 delta-aminolevulinate synthase Yes Yes   [99, 101]
2.3.1.41 3-Oxoacyl-[acyl-carrier protein] synthase Yes Yes   [156, 157]
2.3.1.50 serine-palmitoyl transferase No Yes   [155]
2.4.2.1 Purine-nucleoside phosphorylase Yes No Precursor import (hypoxanthine, xanthine) [158]
2.4.2.8 Hypoxanthine phosphoribosyltransferase Yes No Necessary to block all reactions catalyzed by the enzyme [159161]
2.5.1.15 Dihydropteroate synthase Yes No Precursor import (folate) [162164]
2.5.1.16 Spermidine synthase Yes No Precursor import (spermidine) [165]
2.5.1.18 Glutathione transferase Yes Yes   [166169]
2.5.1.19 3-Phosphoshikimate 1- carboxyvinyltransferase Yes No Precursor import (4-aminobenzoate, folate) [170]
2.5.1.58 Farnesyl-diphosphate Farnesyltransferase No Yes   [171]
2.7.1.32 Choline kinase No No Presumably unspecific off-target effects [78]
2.7.8.3 Ceramide-cholinephosphotransferase Yes Yes   [155]
3.3.1.1 S-adenosyl-l-homocysteine hydrolase Yes Yes   [172175]
3.4.11.1 leucine aminopeptidase Yes No Precursor import (amino acids) [176]
3.4.14.1 dipeptidyl aminopeptidase 1 No No Precursor import (amino acids) [177]
3.4.23.38 plasmepsins (aspartic acid proteases) No No Precursor import (amino acids) [178, 179]
3.4.23.39 plasmepsins (aspartic acid proteases) No No Precursor import (amino acids) [178, 179]
3.5.1.89 N-acetyl glucosaminylphosphatidyli-nositol deacetylase No Yes   [180]
3.5.2.3 dihydroorotase Yes Yes   [96, 137]
3.5.4.4 Adenosine deaminase Yes No Precursor import (hypoxanthine, inosine, xanthine) [181, 182]
4.1.1.17 Ornithine decarboxylase No No Precursor import (spermidine, putrescine); alternative reaction R01152 [183185]
4.1.1.23 Orotidine-5'-phosphate decarboxylase Yes Yes   [8991, 97, 98]
4.1.1.50 Adenosylmethionine decarboxylase No No Precursor import (spermidine) [186]
4.1.2.13 Fructose-bisphosphate aldolase Yes No Presumable main antimalarial effect is impaired host cell invasion [187, 188]
4.2.1.1 carbonic anhydrase Yes Yes   [87]
4.2.1.24 Delta-aminolevulinic acid dehydratase No Yes   [100]
4.2.1.58-61 3-hydroxyacyl-ACP dehydratase Yes Yes   [189]
4.2.3.5 Chorismate synthase Yes No Precursor import (4-aminobenzoate, folate) [92]
4.4.1.5 Lactoylglutathione lyase Yes Yes   [190]
4.6.1.12 2-C-methyl-D-erythritol-2,4- Cyclodiphosphate-synthase No Yes   [86]
5.99.1.2 topoisomerase I Yes Yes   [191]
5.99.1.3 topoisomerase II Yes Yes   [192194]
6.1.1.3 Threonine-tRNA ligase Yes Yes   [195]
6.1.1.7 Alanine-tRNA ligase Yes Yes   [196]
6.3.2.2 Gamma-glutamylcysteine synthetase Yes Yes   [144, 197, 198]
6.3.4.4 Adenylosuccinate synthetase Yes Yes   [199]
6.3.5.2 GMP synthetase No No Necessary to block all reactions catalyzed by the enzyme; precursor import(guanine/guanosine) [200]
6.3.5.5 Carbamoyl-phosphate synthase (glutamine-hydrolysing) No Yes   [88]
6.3.5.8 amino-deoxychorismate synthase No No Precursor import (4-aminobenzoate, folate) [128]
6.4.1.2 Acetyl-CoA carboxylase Yes Yes   [156]