Skip to main content

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

 

[134–136]

1.3.3.1

Dihydroorotate oxidase

No

Yes

 

[92–95, 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

[138–140]

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

 

[147–149]

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

[159–161]

2.5.1.15

Dihydropteroate synthase

Yes

No

Precursor import (folate)

[162–164]

2.5.1.16

Spermidine synthase

Yes

No

Precursor import (spermidine)

[165]

2.5.1.18

Glutathione transferase

Yes

Yes

 

[166–169]

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

 

[172–175]

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

[183–185]

4.1.1.23

Orotidine-5'-phosphate decarboxylase

Yes

Yes

 

[89–91, 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

 

[192–194]

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]