Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Identification of a nucleoside/nucleobase transporter from Plasmodium falciparum, a novel target for anti-malarial chemotherapy.
Parker MD
,
Hyde RJ
,
Yao SY
,
McRobert L
,
Cass CE
,
Young JD
,
McConkey GA
,
Baldwin SA
.
???displayArticle.abstract???
Plasmodium, the aetiologic agent of malaria, cannot synthesize purines de novo, and hence depends upon salvage from the host. Here we describe the molecular cloning and functional expression in Xenopus oocytes of the first purine transporter to be identified in this parasite. This 422-residue protein, which we designate PfENT1, is predicted to contain 11 membrane-spanning segments and is a distantly related member of the widely distributed eukaryotic protein family the equilibrative nucleoside transporters (ENTs). However, it differs profoundly at the sequence and functional levels from its homologous counterparts in the human host. The parasite protein exhibits a broad substrate specificity for natural nucleosides, but transports the purine nucleoside adenosine with a considerably higher apparent affinity (K(m) 0.32+/-0.05 mM) than the pyrimidine nucleoside uridine (K(m) 3.5+/-1.1 mM). It also efficiently transports nucleobases such as adenine (K(m) 0.32+/-0.10 mM) and hypoxanthine (K(m) 0.41+/-0.1 mM), and anti-viral 3'-deoxynucleoside analogues. Moreover, it is not sensitive to classical inhibitors of mammalian ENTs, including NBMPR [6-[(4-nitrobenzyl)thio]-9-beta-D-ribofuranosylpurine, or nitrobenzylthioinosine] and the coronary vasoactive drugs, dipyridamole, dilazep and draflazine. These unique properties suggest that PfENT1 might be a viable target for the development of novel anti-malarial drugs.
Baldwin,
Nucleoside transporters: molecular biology and implications for therapeutic development.
1999, Pubmed
Baldwin,
Nucleoside transporters: molecular biology and implications for therapeutic development.
1999,
Pubmed
Bowman,
The complete nucleotide sequence of chromosome 3 of Plasmodium falciparum.
1999,
Pubmed
Carter,
Isolation and functional characterization of the PfNT1 nucleoside transporter gene from Plasmodium falciparum.
2000,
Pubmed
,
Xenbase
Cass,
Nucleoside transporters of mammalian cells.
1999,
Pubmed
Chan,
Permeation and metabolism of anti-HIV and endogenous nucleosides in human immune effector cells.
1993,
Pubmed
Chan,
Antiviral nucleoside toxicity in canine bone marrow progenitor cells and its relationship to drug permeation.
1992,
Pubmed
Chiang,
The adenosine transporter of Toxoplasma gondii. Identification by insertional mutagenesis, cloning, and recombinant expression.
1999,
Pubmed
,
Xenbase
Crawford,
Cloning of the human equilibrative, nitrobenzylmercaptopurine riboside (NBMPR)-insensitive nucleoside transporter ei by functional expression in a transport-deficient cell line.
1998,
Pubmed
de Koning,
Characterization of a nucleoside/proton symporter in procyclic Trypanosoma brucei brucei.
1998,
Pubmed
Diallinas,
Genetic and molecular characterization of a gene encoding a wide specificity purine permease of Aspergillus nidulans reveals a novel family of transporters conserved in prokaryotes and eukaryotes.
1995,
Pubmed
Domin,
Membrane permeation mechanisms of 2',3'-dideoxynucleosides.
1993,
Pubmed
el Kouni,
Prevention of tubercidin host toxicity by nitrobenzylthioinosine 5'-monophosphate for the treatment of schistosomiasis.
1989,
Pubmed
Gardner,
Chromosome 2 sequence of the human malaria parasite Plasmodium falciparum.
1998,
Pubmed
Gati,
Structural modifications at the 2'- and 3'-positions of some pyrimidine nucleosides as determinants of their interaction with the mouse erythrocyte nucleoside transporter.
1984,
Pubmed
Griffith,
Nucleoside and nucleobase transport systems of mammalian cells.
1996,
Pubmed
Huang,
Cloning and functional expression of a complementary DNA encoding a mammalian nucleoside transport protein.
1994,
Pubmed
,
Xenbase
Huang,
Functional expression of Na(+)-dependent nucleoside transport systems of rat intestine in isolated oocytes of Xenopus laevis. Demonstration that rat jejunum expresses the purine-selective system N1 (cif) and a second, novel system N3 having broad specificity for purine and pyrimidine nucleosides.
1993,
Pubmed
,
Xenbase
Liman,
Subunit stoichiometry of a mammalian K+ channel determined by construction of multimeric cDNAs.
1992,
Pubmed
,
Xenbase
Mackey,
Nucleoside transport and its significance for anticancer drug resistance.
1998,
Pubmed
Mäser,
A nucleoside transporter from Trypanosoma brucei involved in drug resistance.
1999,
Pubmed
McConkey,
Inhibition of Plasmodium falciparum protein synthesis. Targeting the plastid-like organelle with thiostrepton.
1997,
Pubmed
McConkey,
Plasmodium falciparum: isolation and characterisation of a gene encoding protozoan GMP synthase.
2000,
Pubmed
Osses,
Hypoxanthine enters human vascular endothelial cells (ECV 304) via the nitrobenzylthioinosine-insensitive equilibrative nucleoside transporter.
1996,
Pubmed
Penny,
Expression of substrate-specific transporters encoded by Plasmodium falciparum in Xenopus laevis oocytes.
1998,
Pubmed
,
Xenbase
Plagemann,
Nucleoside and nucleobase transport in animal cells.
1988,
Pubmed
Sanchez,
Cloning and functional expression of a gene encoding a P1 type nucleoside transporter from Trypanosoma brucei.
1999,
Pubmed
,
Xenbase
Trager,
Human malaria parasites in continuous culture.
1976,
Pubmed
Trager,
Cultivation of malaria parasites.
1994,
Pubmed
Ullman,
Genetic analysis of 2',3'-dideoxycytidine incorporation into cultured human T lymphoblasts.
1988,
Pubmed
Vasudevan,
Cloning of Leishmania nucleoside transporter genes by rescue of a transport-deficient mutant.
1998,
Pubmed
,
Xenbase
White,
The treatment of malaria.
1996,
Pubmed
Wirth,
Malaria: a 21st century solution for an ancient disease.
1998,
Pubmed
Woodrow,
Intraerythrocytic Plasmodium falciparum expresses a high affinity facilitative hexose transporter.
1999,
Pubmed
,
Xenbase
Yao,
Molecular cloning and functional characterization of nitrobenzylthioinosine (NBMPR)-sensitive (es) and NBMPR-insensitive (ei) equilibrative nucleoside transporter proteins (rENT1 and rENT2) from rat tissues.
1997,
Pubmed
,
Xenbase
Zimmerman,
3'-azido-3'-deoxythymidine. An unusual nucleoside analogue that permeates the membrane of human erythrocytes and lymphocytes by nonfacilitated diffusion.
1987,
Pubmed
