Table 2.

Drug Targets Proposed in the Literature With Biological Evidence, Such as In Vitro Growth Inhibition When Enzyme Inhibited

Target enzyme with evidence
EC number
Reference
Enzymes
Chokepoint
In human
3-oxoacyl-[acyl-carrier protein] synthase 2.3.1.41 Waller et al. 2003 PFB0505c Yes Yes
Carbamoyl-phosphate synthase 6.3.5.5 Flores et al. 1997 PF13_0044 Yes Yes
Choline transport Ancelin et al. 1986 PFL0620c Yes No
Chorismate synthase 4.2.3.5 McRobert and McConkey 2002 MAL6P1.199 Yes No
DNA-directed DNA polymerase 2.7.7.7 Barker Jr. et al. 1996 11 proteins Yes Yes
Enoyl-[acyl-carrier protein] reductase (NADH) 1.3.1.9 Surolia and Surolia 2001 MAL6P1.275 Yes No
Farnesyl-diphosphate famesyltransferase 2.5.1.21 Chakrabarti et al. 2002 PF11_0483 Yes Yes
Fructose-bisphosphate aldolase 4.1.2.13 Wanidworanun et al. 1999 PF14_0425 Yes Yes
Gamma-glutamylcysteine synthetase 6.3.2.2 Meierjohann et al. 2002 PFI0925w Yes Yes
Histone deacetylase Darkin-Rattray et al. 1996 PF10_0078 Yes Yes
PF14_0690
PF11_1260c
Hypoxanthine phosphoribosyltransferase 2.4.2.8 Dawson et al. 1993 PF10_0121 Yes Yes
IMP dehydrogenase 1.1.1.205 Webster et al. 1982 PFI1020c No Yes
Lactoylglutathione lyase 4.4.1.5 Thornalley et al. 1994 PF11_0145 Yes Yes
MAL6P1.50
Lysophospholipase 3.1.1.5 Zidovetzki et al. 1994 PF07_0005 Yes No
PF07_0040
PF14_0738
PF14_0737
PF14_0017
NADH dehydrogenase (ubiquinone) 1.6.5.3 Krungkrai et al. 2002 PFC0505c Yes No
Purine nucleoside phosphorylase 2.4.2.1 Kiscka et al. 2002 PFE0660c Yes No
Ribonucleoside Reductase 1.17.4.1 Chakrabarti et al. 1993 PF10_0154 Yes Yes
PF14_0352
PF14_0053
RNA Polymerase 2.7.7.6 Lin et al. 2002 24 proteins Yes Yes
S-adenosyl-L-homocysteine hydrolase 3.3.1.1 Shuto et al. 2002 PFE1050w Yes Yes
S-adenosylmethionine decarboxylase 4.1.1.50 Wright et al. 1991 PF10_0322 Yes Yes
Sphingomyelinase 3.1.4.12 Hanada et al. 2002 PFL1870c Yes No
Succinate dehydrogenase 1.3.99.1 Suraveratum et al. 2000 PFL0630w No Yes
PF10_0334
Thioredoxin reductase (NADPH) 1.8.1.9 Krnajski et al. 2002 PFI1170c No Yes
Thymidylate synthase
2.1.1.45
Jiang et al. 2000
PFD0830w
Yes
Yes

[i] The reaction and its EC number are given as well as the Protein Identifiers for the corresponding enzymes (for enzymatic reactions catalyzed by more than 10 proteins, see http://plasmocyc.stanford.edu). The In Human column denotes whether or not the enzymatic activity has a similar enzyme in human as determined by BLAST alignment with an expectation of less than 0.0001. Of these 24 reactions, 21 (87.5%) were identified as chokepoints.