Drug Targets for Plasmodium falciparum

compiled by Iwei Yeh

Drug Target

E.C. number

Relevant Drugs

References

1-deoxy-D-xylulose 5-phosphate reductoisomerase

1.1.1.267

fosmidomycin

Wiesner J, Borrmann S, Jomaa H. Fosidomycin for the treatment of malaria. Parasitol Res. 2003 Jun;90 Suppl 2:S71-6.

dihydrofolate reductase

1.5.1.3

pyrimethamine, cycloguanil

Sixsmith DG, Watkins WM, Chulay JD, Spencer HC. In vitro antimalarial activity of tetrahydrofolate dehydrogenase inhibitors. Am J Trop Med Hyg. 1984 Sep;33(5):772-6.

dihydropteroate synthase

2.5.1.15

sulfone/sulfonamide grugs

Triglia T, Cowman AF. Primary structure and expression of the dihydropteroate synthetase gene of Plasmodium falciparum. Proc Natl Acad Scie USA. 1994 Jul 19;91(15):7149-53.

Proposed Target

E.C. number

Reasons

References

1-deoxy-D-xylulose-5-phosphate synthase

2.2.1.7

inhibition of its pathway by fosmidomycin suppresses in vitro growth

Lichtenthatler HK, Non-mevalonate isoprenoid biosynthesis: enzymes, genes and inhibitors. Biochem Soc Trans. 2000 Dec; 28(6):785-9.

2C-methyl-D-erythritol 2,4-cyclodiphosphate synthase

4.6.1.12

essential in E. coli, part of nonmevalonate pathway of isoprenoid biosynthesis

Kemp LE, Bond CS, Hunter WN. Structure of 2C-methyl-D-erythritol 2,4-cyclophosphate synthase: an essential enzyme for isoprenoid biosynthesis and target for antimicrobial drug development. Proc Natl Acad Sci USA. 2002 May 14;99(10):6591-6.

4-diphosphocytidyl-2C-methyl-D-erythritol kinase

2.7.1.148

essential in E. coli, part of nonmevalonate pathway of isoprenoid biosynthesis, critical yet distinct from human pathways

Kemp LE, Bond CS, Hunter WN. Structure of 2C-methyl-D-erythritol 2,4-cyclodiphosphate synthase: an essential enzyme for isoprenoid biosynthesis and target for antimicrobial drug development. Proc Natl Acad Sci USA. 2002 May 14;99(10):6591-6

acetyl-CoA carboxylase

6.4.1.2

part of apicoplast de novo fatty acid biosynthetic pathway, and responds to inhibitors identified for bacteria and plants

Gornicki P. Apicoplast fatty acid biosynthesis as a target for medical intervention in apicomplexan parasites.Int J Parasitol. 2003 Aug;33(9);885-96.

acetyl-CoA synthetase

6.2.1.1

no homologue in human

Sanchez LB, Galperin MY, Muller M. Acetyl-CoA synthetase from the amitochondrate eukaryote Giardia lamblia belongs to the newly recognized superfamily of acyl-CoA synthetases (Nucleoside diphosphate-forming). J Biol Chem. 2000 Feb 25; 275(8):5794-803

acyl-CoA synthetase

6.2.1.3

stage-specifc expression in human stages and differences between human and parasite sequences

Matesanz F, Tellez MM, Alcina A. The Plasmodium falciparum fatty acyl-CoA synthetase family (PfACS) and differential stage-specific expression in infected erythrocytes. Mol Biochem Parasitol. 2003 Jan;126(1):109-12

adenosine deaminase

3.5.4.4

L-nucleosides selectively enter malaria infected erythrocytes and are metabolized by adenosine deaminase; novel L-nucleosides may act as potential anti-malarials

Gero AM, Perrone G, Brown DM, Hall ST, Chu CK. L-purine nucleosides as selective antimalarials. Nucleosides Nucleotides. 1999 Apr-May;18(4-5):885-9.

adenylosuccinate lyase

4.3.2.2

believed to be part of parasite de novo purine nucleotide synthesis; inhibition of pyrimidine biosynthesis is therapeutic

Marshall VM, Coppel, RL. Characterization of the gene encoding adenylosuccinate lyase of Plasmodium falciparum. Mol Biochem Parasito. 1997 Sep;88(1-2):237-41.

adenylosuccinate synthase

6.3.4.4

part of purine salvage pathway and parasite does not have de novo purine biosynthesis pathway

Jayalakshmi R, Sumathy K, Balaram H. Purification and characterization of recombinant Plasmodium falciparum adenylosuccinate synthetase expressed in Escherichia coli. Protein Expr Purif. 2002 Jun;25(1):65-72.

aldolase

4.1.2.13

antisense oligonucleotides inhibit asexual erythrocytic stages

Wanidworanun C, Nagel RL, Shear HL. Antisense oligonucleotides targeting malarial aldolase inhibit the asexual erythrocytic stages of Plasmodium falciparum. Mol Biochem Parasitol. 1999 Jul 20;102(1):91-101.

DNA-(apurinic or apyrimidinic site) lyase

4.2.99.18

parasite has different biology than mammalian cells for repaining apurinic/apyrimidinic sites on DNA

Haltiwanger BM, Karpinich NO, Taraschi TF. Characterization of class II apurinic/apyrimidinic endonuclease activities in the human malaria parasite, Plasmodium falciparum. Biochem J. 2000 Jan 1;345 Pt 1:85-9.

aspartate carbamoyltransferase

2.1.3.2

active in trophozoite stage, part of de novo pyrimidine synthesis

Gero AM, Brown GV, O'Sullivan WJ. Pyrimidine de novo synthesis during the life cycle of the intraerythrocytic stage of Plasmodium falciparum. J Parasitol. 1984 Aug;70(4):536-41.

beta-ketoacyl-ACP reductase

1.1.1.100

growth inhibited by cerulenin, an inhibitor

Waller RF, Ralph SA, Reed MB, Su V, Douglas JD, Minnikin DE, Cowman AF, Besra GS, McFadden GI. A type II pathway for fatty acid biosynthesis presents drug targets in Plasmodium falciparum. Antimicrob Agents Chemother. 2003 Jan; 47(1):297-301.

beta-ketoacyl-ACP synthase

2.3.1.41

growth inhibited by cerulenin, an inhibitor

carbamoyl phosphate synthetase

6.3.5.5

inhibition with targeted ribozymes correlate with expression in the parasite and reduced viability in culture

Flores MV, Atkins D, Wade D, O'Sullivan WJ, Stewart TS. Inhibition of Plasmodium falciparum proliferation in vitro by ribozymes. J Biol Chem. 1997 Jul 4; 272(27):16940-5.

choline kinase

2.7.1.32

inhibition impairs choline transport which inhibits in vitro growth

Ancelin ML, Vial HJ. Quaternary ammonium compounds efficiently inhibit Plasmodium falciparum growth in vitro by impairment of choline transport. Antimicrob Agents Chemother. 1986 May; 29(5):814-20.

chorismate synthase

4.2.3.5

RNA interference of this activity inhibits growth

McRobert L, McConkey GA. RNA iterference (RNAi) inhibits growth of Plasmodium falciparum. Mol Biochem Parasitol. 2002 Feb;119(2):273-8.

cholinephosphate cytidylyltransferase

2.7.7.15

substantial diffences from mammalian and yeast counterparts with respect to sequence and regulation of activity

Olliaro PL, Yuthavong Y. An overview of chemotherapeutic targets for antimalarial drug discovery. Pharmacol Ther. 1999 Feb; 81(2):91-110.

CTP synthase

6.3.4.2

differences between parasite enzyme and human enzyme

Hendriks EF, O'Sullivan WJ, Stewart TS. Molecular cloning and characterization of the Plasmodium falciparum cutidine triphosphate synthetase gene. Biochim Biophys Acta. 1998 Aug 20;1399(2-3):213-8.

cytochrome C oxidase

1.9.3.1

different activity and inhibition from mammalian forms

Krungkrai J, Krungkrai SR, Suraveratum N, Prapunwattana P. Mitochondrial uniquinol-cytochrome c reductase and cytochrome c oxidase: chemotherapeutic targets in malarial parasites. Biochem Mol Biol Int. 1997 Aug;42(5):1007-14.

delta-aminolevulinate dehydratase

4.2.1.24

distinct immunological identity and inhibitor specificity

Varadharajan S, Dhanasekaran S, Bonday ZQ, Rangarajan PN, Padmanaban G. Involvement of delta-aminolaevulinate synthase encoded by the parasite gene in de novo haem synthesis by Plasmodium falciparum. Biochem J. 2002 Oct 15; 367(pt 2):321-7.

deoxyhypusine synthase

2.5.1.46

inhibited by triclosan which inhibits growth in vitro

Surolia, N, Surolia A. Triclosan offers protection against blood stages of malaria by inhibiting enoyl-ACP reductase of Plasmodium falciparum. Nat Med 2001 Feb;7(2):167-73.

dihydrofolate synthase

6.3.2.12

importance of pathway and dissimilarity with human

Lee CS, Salcedo E, Wang Q, Wang P, Sims PF, Hyde JE. Characterization of tree genes encoding enzymes of the folate biosynthetic pathway in Plasmodium falciparum. Parasitology. 2001 Jan; 122 Pt 1:1-13.

dihydroorotase

3.5.2.3

inhibitors inhibit growth in vitro and eliminate parasitemia in mice, different inhibition than in human

Krungkrai J, Krungkrai SR, Phakanont K. Antimalarial activity of orotate analogs that inhibit dihydroorotase and dihydroorotate dehydrogenase. Biochem Pharmacol. 1992 Mar 17; 43(6):1295-301.

dihydroorotate dehydrogenase

1.3.99.11

inhibitors inhibit growth in vitro and eliminate parasitemia in mice, different inhibition than in human

Krungkrai J, Krungkrai SR, Phakanont K. Antimalarial activity of orotate analogs that inhibit dihydroorotase and dihydroorotate dehydrogenase. Biochem Pharmacol. 1992 Mar 17; 43(6):1295-301.

DNA polymerase

2.7.7.7

inhibition by targeted antisense oligodeoxynucleotides

Barker RH Jr, Metelev V, Rapaport E, Zamecnik P. Inhibition of Plasmodium falciparum malaria using antisense oligodeoxynucleotides. Proc Natl Acad Sci USA. 1996 Jan 9;93(1):514-8.

enoyl-ACP-reductase

1.3.1.9

pathway resides in apicoplast, not present in humans

Kuo MR, Morbidoni HR, Alland D, Sneddon SF, Gourlie BB, Staveski MM, Leonard M, Gregory JS, Janjigian AD, Yed C, Musser JM, Kreiswirth B, Iwamoto H, Perozzo R, Jacobs WR jr, Sacchettini JC, Fidock DA. J Biol Chem. 2003 Jun 6;278(23):20851-9.

ferredoxin NADP reductase

1.18.1.2

role in redox system

Vollmer M, Thomsen N, Wiek S. Seeber F. Apicomplexan parasites possess distinct nuclear-encoded, but apicoplast-localized, plant-type ferredoxin-NADP+ reductase and ferredoxin. J Biol Chem. 2001 Feb 23;276(8):5483-90.

folylpolyglutamate synthase

6.3.2.17

importance of pathway and dissimilarity with human

gamma-glutamylcysteine synthetase

6.3.2.2

inhibitor buthionin sulphozimine kills erythrocytic stages

Meierjohann S, Walter RD, Muller S. Glutathione synthetase from Plasmodium falciparum. Biochem J. 2002 May 1;363(pt 3):833-8.

glutathione reductase

1.8.1.7

role in antioxidative defense and maintaining reducing environment of cytosol

Becker K, Rahlfs S, Nickel C, Schirmer RH. Glutathione--functions and metabolism in the malarial parasite Plasmodium falciparum. Biol Chem. 2003 Apr384(4):551-66.

glutathione-S transferase

2.5.1.18

role in antioxidative defense and maintaining reducing environment of cytosol

Becker K, Rahlfs S, Nickel C, Schirmer RH. Glutathione--functions and metabolism in the malarial parasite Plasmodium falciparum. Biol Chem. 2003 Apr384(4):551-66.

serine hydroxymethyltransferase

2.1.2.1

role in methylenetetrahydrofolate recycling

Alfadhli S. Rathod PK. Gene organization of a Plasmodium falciparum serine hydroxymethyltransferase and its functional expression in Escherichia coli. Mol Biochem Parasitol. 2000 Oct;110(2):283-91.

glyoxylase

4.4.1.5

inhibition by S-p-bromobenzylglutathione diethyl ester induces parasite toxicity in culture

Thornalley PJ, Strath M, Wilson RJ. Antimalarial activity in vitro of the glyoxalase I inhibitor diester, S-p-bromobenzylglutathione diethyl ester. Biochem Pharmacol. 1994 Jan 20;47(2):418-20.

hexokinase

2.7.1.1

key enzyme of glycolysis, invertebrate type

Olafsson P. Matile H, Certa U. Milecular analysis of Plasmodium falciparum hexokinase. Mol Biochem Parasitol. 1992 Novl56(1):89-101.

histone deacetylase

none

inhibited by apicidin which is active against Plasmodium berghei in mice

Darkin-Rattray SJ, Gurnett AM, Myers RW, Dulski PM, Crumley TM, Allocco JJ, Cannova C, Meinke PT, Colletti SL, Bednarek MA, Singh SB, Goetz MA, Dombrowski AW, Polishook JD, Schmatz DM. ApicidinL a novel antiprotozoal agent that inhibits parasite histone deacetylase. Proc Natl Acad Sci USA. 1996 Nov 12;93(23):13143-7.

homospermidine synthase

2.5.1.44

importance of polyamine metabolism and availability of inhibitors

Kaiser AE, Gottwald AM, Wiersch CS, Maier WA, Seitz HM. Spermidine metabolism in parasitic protozoa--a comparison to the situation in prokaryotes, viruses, plants and fungi. Folia Parasitol (Praha). 2003 Mar;50(1):3-18.

hypoxanthine guanine phosphoribosyltransferase

2.4.2.8

inhibition by antisense oligos kills parasites in vitro

Dawson PA, Cochran DA, Emmerson BT, Gordon RB. Inhibition of Plasmodium falciparum hypoxanthine-guanine phosphoribosyltransferase mRNA by antisense oligodeoxynucleotide sequence. Mol Biochem Parasitol. 1993 Jul;60(1):153-6.

IMP dehydrogenase

1.1.1.205

inhibition by bredinin which arrests trophozoite growth in culture

Webster HK, Whaun JM. Antimalarial properties of bredinin. Prediction based on identification of differences in human host-parasite purine metabolism. J. Clin Invest. 1982 Aug;70(2):461-9.

lactate dehydrogenase

1.1.1.27

unique cleft near active site

Dunn CR, Banfield MJ, Barker JJ, Higham CW, Moreton KM, Turgut-Balik D, Brady RL, Holbrook JJ. The structure of lactate dehydrogenase from Plasmodium falciparum reveals a new target for anti-malarial design. Nat Struct Biol. 1996 Nov;3(11):912-5.

leucine aminopeptidase

3.4.11.1

inhibitors block growth in vitro

Nankya-Kitaka MK, Curley GP, Gavigan CS, Bell A, Dalton JP. Plasmodium chabaudi chabaudi and P. falciparum: inhibition of aminopeptidase and parasite growth by bestatin and nitrobestatin. Parasitol Res. 1998 Jul;84(7):552-8.

lysophospholipase

3.1.1.5

inhibited by thimerosal which decreases parasitaemia in culture

Zidovetzki R, Sherman IW, Prudhomme J, Crawford J. Inhibition of Plasmodium falciparum lysophospholipase by anti-malarial drugs and sulphydryl reagents. Parasitology. 1994 Apr;108 (Pt 3):249-55.

mitochondrial NADH dehydrogenase

1.6.5.3

inhibited by rotenone and plumbagin which have antimalarial activity in vitro

Krungkrai J, Kanchanarithisak R, Krungkrai SR, Rochanakij S. Mitochondrial NADH dehydrogenase from Plasmodium falciparum and Plasmodium berghei. Exp Parasitol. 2002 Jan;100(1):54-61.

mitochondrial ubiquinol-cytochrome C reductase

1.10.2.2

more sensitive to inhibition by quinolones than mammalian enzyme

N-acetylglucosaminylphosphotidylinositol deacetylase

3.5.1.89

different activity than human forms, Plasmodium-specific inhibitors

Smith TK, Gerold P, Crossman A, Paterson MJ, Borissow CN, Brimacombe JS, Ferguson MA, Schwarz RT. Substrate specificity of the Plasmodium falciparum glycosylphosphatidylinositol biosynthetic pathway and inhibition by species-specific suicide substrates. Biochemistry. 2002 Oct 15;41(41):12395-406.

N-myristoyltransferase

2.3.1.97

different inhibition from human enzyme, drug target for fungi

Gunaratne RS, Sajid M, Ling IT, Tripathi R, Pachebat JA, Holder AA. Characterization of N-myristoyltransferase from Plasmodium falciparum. Biochem J. 2000 Jun 1;348 Pt 2:459-63.

orotate phosphoribosyltransferase

2.4.2.10

different inhibition from human enzyme

Rathod PK, Reyes P. Orotidylate-metabolizing enzymes of the human malarial parasite, Plasmodium falciparum, differ from host cell enzymes. J Biol Chem. 1983 Mar 10;258(5):2852-5.

orotidine-5'-phosphate decarboxylase

4.1.1.23

different inhibition from human enzyme

Rathod PK, Reyes P. Orotidylate-metabolizing enzymes of the human malarial parasite, Plasmodium falciparum, differ from host cell enzymes. J Biol Chem. 1983 Mar 10;258(5):2852-5.

peptide deformylase

3.5.1.88

absent from mammalian cells

Meinnel T. Peptide deformylase of eukaryotic protists: a target from new antiparasitic agents? Parasitol Today. 2000 Apr; 16(4):165-8.

peptidyl-prolyl cis-trans isomerase

5.2.1.8

target of cyclosporin activity, may mediate its anti-malarial properties

Gavigan CS, Kiely SP, Kirtzlin J, Bell A. Cyclosporin-binding proteins of Plasmodium falciparum. Int J Parasitol. 2003 Aug;33(9):987-96.

phosphoribosyl pyrophosphate synthase

2.7.6.1

inhibition from low GSH thought to account for decreased parasite growth under oxidative stress

Roth EF, Ruprecht RM, Schulman S, Vanderberg J, Olson JA. Ribose metabolism and nucleic acid synthesis in normal and glucose-6-phosphate dehydrogenase-deficient human erythrocytes infected with Plasmodium falciparum. J Clin Invest. 1986 Apr;77(4):1129-35.

protein farnesyltransferase

2.5.1.21

inhibition inhibits growth in vitro

Chakrabarti D, Da Silva T, Barger J, Paquette S, Patel H, Patterson S, Allen CM. Protein farnesyltransferase and protein prenylation in Plasmodium falciparum. J Biol Chem. 2002 Nove 1l277(44):42066-73.

purine nucleoside phosphorylase

2.4.2.1

inhibitor inhibits growth in vitro

Kicska GA, Tyler PC, Evans GB, Furneaux RH, Schramm VL, Kim K. Purine-less death in Plasmodium falciparum induced by immucillin-H, a transition state analogue of purine nucleoside phosphorylase. J Biol Chem. 2002 Feb 1;277(5):3226-31.

ribonucleotide reductase

1.17.4.1

antisense oligonucleotide inhibits growth in vitro

Chakrabarti D, Schuster SM, Chakrabarti R. Cloning and characterization of subunit genes of ribonucleotide reductase, a cell-cycle-regulated enzyme, from Plasmodium falciparum. Proc Natl Acad Sci USA. 1993 Dec 15;90(24):12020-4.

RNA guanyltransferase

2.7.7.50

part of a fungi/viral family

Ho CK, Shuman S. A yeast-like mRNA capping apparatus in Plasmodium falciparum. Proc Natl Acad Sci USA. 2001 Mar 13;98(6):3050-5.

RNA polymerase

2.7.7.6

inhibition of mitochondrial form with minocycline which is effective against drug resistant strains in vitro

Lin Q, Katakura K, Suzuki M. Inhibition of mitochondrial and plastid activity of Plasmodium falciparum by minocycline. FEBS Lett. 2002 Mar 27;515(103):71-4.

S-adenosyl-L-homocysteine hydrolase

3.3.1.1

inhibitor has antimalarial effect against P. berghei in mice

Shuto S, Minakawa N, Niizuma S, Kim HS, Wataya Y, Matsuda A. New neplanocin analogues. 12. Alternative synthesis and antimalarial effect of (6'R)-6'-C-methylneplanocin A, a potent AdoHcy hydrolase inhibitor. J Med Chem. 2002 Jan 31;45(3):748-51.

S-adenosylmethionine decarboxylase

4.1.1.50

irreversible inhibition causes growth inhibition in vitro

Wright PS, Byers TL, Corss-Doersen DE, McCann PP, Bitonti AJ. Irreversible inhibition of S-adenosylmethionine decarboxylase in Plasmodium falciparum-infected erythrocytes: growth inhibition in vitro. Biochem Pharmacol. 1991 Jun 1;41(11):1713-8.

S-adenosylmethionine synthetase

2.5.1.6

closely related to protozoan and plant forms, different sensitivity to inhibitors than human form

Chiang PK, Chamberlin ME, Nicholson D, Soubes S, Su X,Subramanian G, Lanar DE, Prigge ST, Scovill JP, Miller LH, Chou JY. Molecular characterization of Plasmodium falciparum S-adnosylmethionine synthetase. Biochem J. 1999 Dec 1; 344 Pt 2:571-6.

sphingomyelin synthase

2.7.8.3

inhibition blocks parasite growth in culture

Lauer SA, Ghori N, Haldar K. Sphingolipid synthesis as a target for chemotherapy against malaria parasites. Proc Natl Acad Sci USA. 1995 Sep 26;92(20):9181-5.

sphingomyelinase

3.1.4.12

principal enzyme in sphingomyelinase metabolism, inhibition with scyphostatin causes impairment of intraerythrocytic development

Hanada K, Palacpac NM, Magistrado PA, Kurokawa K, Rai G, Sakata D, Hara T, Horii T, Nishijima M, Mitamura T. Plasmodium falciparum phospholipase C hydrolyzing sphingomyelin and lysocholinephospholipids is a possible target for malaria chemotherapy. J. Exp Med. 2002 Jan 7;195(1):23-24.

succinate dehydrogenase

1.3.99.1

different inhibition than in human, inhibitors slow growth in vitro

Suraveratum N, Krungkrai SR, Leangaramgul P, Prapunwattana P, Krungkrai J. Purification and characterization of Plasmodium falciparum succinate dehydrogenase. Mol Biochem Parasitol. 2000 Feb 5;105(2):215-22.

superoxide dismutase

1.15.1.1

no apparent phylogenetic relationship to human

Baert CB, Deloron P, Viscogliosi E, Delgado-Viscogliosi P, Camus D, Dive D. Coning and characterization of iron-containing superoxide dismutase from the human malaria species Plasmodium ovale, P. malariae and P. vivax. Parasitol Res. 1999;85(12):1018-24.

telomerase

none

activity in all intraerythrocytic stages, inhibited by berberine

Sriwilaijareon N, Petmitr S. Mutirangura A, Ponglikitmongkol M, Wilairat P. Stage specificity of Plasmodium falciparum telomerase and its inhibition by berberine.

thioredoxin reductase

1.8.1.9

essential for survival of erythrocytic stages

Krnajski Z, Gilberger TW, Walter RD, Cowman AF, Muller S. Thioredoxin reductase is essential for the survival of Plasmodium falciparum erythrocytic stages. J Biol Chem. 2002 Jul 19;277(29):25970-5.

thymidylate synthase

2.1.1.45

inhibitor has in vitro activity against parasite

Jiang L, Lee PC, White J, Rathod PK. Potent and selective activity of a combination of thymidine and 1843U89, a folate-based thymidylate synthase inhibitor, against Plasmodium falciparum. Antimicrob Agents Chemother. 2000 Apr;44(4):1047-50.

topoisomerase I

5.99.1.2

activity especially in schizont stage, availability of inhibitors

Tosh K, Cheesman S, Horrocks P, Kilbey B. Plasmodium falciparum: stage-related expression on topoisomerase I. Exp Parasitol. 1999 Feb;91(2):126-32.

topoisomerase II

5.99.1.3

sensitive to fluoroquinolones

Chavalitshewinkoon-Petmitr P, Worasing R, Wilairat P. Partial purification of mitochondrial DNA topoisomerase II from Plasmodium falciparum and its sensitivity to inhibitors. Southeast Asian J Trop Med Public Health. 2001 Dec;32(4):733-8.

triosephosphate isomerase

5.3.1.1

parasite specific structural features

Subbayya IN, Ray SS, Balaram P, Balaram H. Metabolic enzymes as potential drug targets in Plasmodium falciparum. Indian J Med Res. 1997 Aug;106:79-94.

amino-acyl tRNA synthetases:

universal and essential

Schimmel P, Tao J, Hill J. Aminoacyl tRNA synthetases as targets for new anti-infectives. FASEB J. 1998 Dec;12(15):1599-609.

alanine--tRNA ligase

6.1.1.7

arginine--tRNA ligase

6.1.1.19

asparagine--tRNA ligase

6.1.1.22

aspartate--tRNA ligase

6.1.1.12

cysteine--tRNA ligase

6.1.1.16

glutamate--tRNA ligase

6.1.1.17

glutamine--tRNA ligase

6.1.1.18

glycine--tRNA ligase

6.1.1.14

histidine--tRNA ligase

6.1.1.21

isoleucine--tRNA ligase

6.1.1.5

leucine--tRNA ligase

6.1.1.4

lysine--tRNA ligase

6.1.1.6

methionine--tRNA ligase

6.1.1.10

phenylalanine--tRNA ligase

6.1.1.20

proline--tRNA ligase

6.1.1.15

threonine--tRNA ligase

6.1.1.3

serine--tRNA ligase

6.1.1.11

tryptophan--tRNA ligase

6.1.1.2

tyrosine--tRNA ligase

6.1.1.1

valine--tRNA ligase

6.1.1.9

Proteases:

plasmepsin I

3.4.23.38

inhibition results in growth inhibition in culture

Noteberg D, Hamelink E, Hulten J, Wahlgren M, Vrang L, Samuelsson B, Hallberg A. Design and synthesis of plasmepsin I and plasmepsin II inhibitors with activity in Plasmodium falciparum-infected cultured human erythrocytes. J Med Chem. 2003 Feb 27;46(5):734-46.

plasmepsin II

3.4.23.39

inhibition results in growth inhibition in culture

Silva AM, Lee AY, Gulnik SV, Maier P, Collins H, Bhat TN, Collins PJ, Cachau RE, Luker KE, Gluzman IY, Francis SE, Oksman A, Goldberg DE, Erickson JW. Structure and inhibition of plasmepsin II, a hemoglobin-degrading enzyme from Plasmodium falciparum. Proc Natl Acad Sci USA. 1996 Sep 17;93(19):10034-9.

Last modified: Mon Sep 01 16:45:35 Pacific Daylight Time 2003