Download Supplementary Table 10

Supplementary Table 10. Potential drug targets in C. hominis
Gene
Type I fatty acid synthase (CpFAS1)
Acetyl-CoA carboxylase
Fatty acyl-CoA synthetase (LCFA)
Type I polyketide synthase
CTP synthase
dUTPase
Ribonucleotide reductase
Inosine 5’ monophosphate dehydrogenase
Thymidine kinase
Thymidylate synthase-dihydrofolate reductase (TSDHFR)
Arginine decarboxylase
Spermidine:spermine-N1-acetyltransferase (SSAT)
Pyruvate–NADP oxidoreductase (PNO)
PPi-phosphofructokinase
Glycolitic enzymes (e.g. lactate dehydrogenase)
Alternative oxidase (CpAOX)
CpATPase3 (Type V P-ATPases)
ATP-binding cassette
Sugar or nucleotide-sugar transport (12)a
Function
Fatty acid biosynthesis
Fatty acid biosynthesis
Fatty acid metabolism
Polyketides biosynthesis
Nucleotide metabolism
Nucleotide metabolism
Purine metabolism
Nucleotide salvage
Nucleotide salvage
DNA synthesis
ORFs
Chro.30258
Chro.80425
Chro.40386
Chro.40330
Chro.50211
Chro.70577
Chro.60090
Chro.60012
Chro.50398
Chro.40506
Ref
[1]
[2]
[3]
[4]
[5]
[5]
[6]
[7]
[7]
[8]
Polyamine biosynthesis
Polyamine biosynthesis
Energy metabolism
Energy metabolism
Energy metabolism
Aerobic respiratory chain
Transporter system
Transporter system
Transporter system
[9]
[9]
[10]
[11]
[5]
[12]
[13]
[14]
[15]
Amino acid transport (5) a
ABC family transport (23) a
Transporter system
Transporter system
NF
NF
Chro.40087
Chro.20231
Chro.70063
Chro.30354
Chro.20456
Chro.60540
Chro.30458
Chro.20067
Chro.40323
Chro.80431
Chro.20017
Chro.10084
Chro.60540
Chro.60563
Chro.50340
Proteinases (e.g. cryptopain)
Host cell invasion
Acidocalcisomes related (e.g.Vacuolar H+-ATPase
Ca+ Storage
subunit D)
Anti-oxidant enzymes (e.g thioredoxin reductase)
Thioredoxin redox cycle
Chro.20464
Membrane protein (e.g. TRAP)
Structural
Chro.10390
Tubulin
Structural
Chro.40322
a Number of possible transporters encoded by C. hominis genome, a few ORFs examples are shown;
NF, not found.
[16]
[17]
[18; 19]
[5;17]
[5]
[20;21]
Reference:
[1] Zhu, G. et al. Expression and functional characterization of a giant Type I fatty acid synthase (CpFAS1) gene from
Cryptosporidium parvum. Mol. Biochem. Parasitol. 134, 127-135 (2004).
[2] Zuther, E. et al. Growth of Toxoplasma gondii is inhibited by aryloxyphenoxypropionate herbicides targeting acetyl-CoA
carboxylase. Proc. Natl. Acad. Sci. U. S. A 96, 13387-13392 (1999).
[3] Camero, L. et al. Characterization of a Cryptosporidium parvum gene encoding a protein with homology to long chain fatty
acid synthetase. J. Eukaryot. Microbiol. 50 Suppl, 534-538 (2003).
[4] Zhu, G. et al. Cryptosporidium parvum: the first protist known to encode a putative polyketide synthase. Gene 298, 79-89
(2002)
[5] Strong, W. B. & Nelson,R.G. Gene discovery in Cryptosporidium parvum: expressed sequence tags and genome survey
sequences. Contrib. Microbiol. 6, 92-115 (2000).
[6] Akiyoshi, D. E. et al. Molecular characterization of ribonucleotide reductase from Cryptosporidium parvum. DNA Seq. 13(3),
167-72 (2002).
[7] Striepen, B. et al. Gene transfer in the evolution of parasite nucleotide biosynthesis. Proc. Natl. Acad. Sci. U. S. A 101,
3154-3159 (2004).
[8] Atreya, C. E. & Anderson, K. S. Kinetic characterization of bifunctional thymidylate synthase-dihydrofolate reductase (TSDHFR) from Cryptosporidium hominis: A paradigm shift for TS activity and channeling behavior. J Biol Chem. 30;279(18),
18314-18322 (2004).
[9] Keithly, J. S. et al. Polyamine biosynthesis in Cryptosporidium parvum and its implications for chemotherapy. Mol.
Biochem. Parasitol. 88(1-2), 35-42 (1997).
[10] Rotte, C. et al. Pyruvate : NADP+ oxidoreductase from the mitochondrion of Euglena gracilis and from the apicomplexan
Cryptosporidium parvum: a biochemical relic linking pyruvate metabolism in mitochondriate and amitochondriate protists.
Mol. Biol. Evol. 18, 710-720 (2001).
[11] Denton, H. et al. Comparison of the phosphofructokinase and pyruvate kinase activities of Cryptosporidium parvum,
Eimeria tenella and Toxoplasma gondii. Mol. Biochem. Parasitol. 76(1-2), 23-29 (1996).
[12] Suzuki, T. et al. Direct evidence for cyanide-insensitive quinol oxidase (alternative oxidase) in apicomplexan parasite
Cryptosporidium parvum: phylogenetic and therapeutic implications. Biochem. Biophys. Res. Commun. 23;313(4), 10441052 (2004).
[13] LaGier, M. J. et al. Characterisation of a novel transporter from Cryptosporidium parvum. Int. J. Parasitol. 32(7), 877-887
(2002).
[14] Perkins, M. E. et al. Cyclosporin analogs inhibit in vitro growth of Cryptosporidium parvum. Antimicrob. Agents
Chemother. 42(4), 843-848 (1998).
[15] Blikslager A et al. Glutamine transporter in crypts compensates for loss of villus absorption in bovine cryptosporidiosis.
Am. J. Physiol. Gastrointest. Liver Physiol. 281(3):G645-53 (2001).
[16] Zapata F. et al. The Cryptosporidium parvum ABC protein family. Mol. Biochem. Parasitol. 120(1):157-161 (2002).
[17] Coombs, G. H. & Muller S. Recent advances in the search for new anti-coccidial drugs. Int. J. Parasitol. 32(5), 497-508
(2002).
[18] Moreno, B. et al. (31)P NMR of apicomplexans and the effects of risedronate on Cryptosporidium parvum growth.
Biochem. Biophys. Res. Commun. 284(3), 632-637 (2001)
[19] Moreno, S. N. & Docampo, R. Calcium regulation in protozoan parasites. Curr. Opin. Microbiol. 6(4), 359-64 (2003).
[20] Fayer, R. & Fetterer, R. Activity of benzimidazoles against cryptosporidiosis in neonatal BALB/c mice. J. Parasitol. 81(5),
794-795 (1995).
[21] Armson, A. et al. A comparison of the effects of two dinitroanilines against Cryptosporidium parvum in vitro and in vivo in
neonatal mice and rats. FEMS Immunol. Med. Microbiol. 26(2), 109-13 (1999).