| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
J Biol Chem, Vol. 275, Issue 14, 10683-10691, April 7, 2000
From the Plasmodium falciparum,
the causative agent of the most lethal form of human malaria, is
incapable of de novo purine synthesis, and thus, purine
acquisition from the host is an indispensable nutritional requirement.
This purine salvage process is initiated by the transport of preformed
purines into the parasite. We have identified a gene encoding a
nucleoside transporter from P. falciparum, PfNT1, and analyzed its function and expression during
intraerythrocytic parasite development. PfNT1 predicts a
polypeptide of 422 amino acids with 11 transmembrane domains that is
homologous to other members of the equilibrative nucleoside transporter
family. Southern analysis and BLAST searching of The
Institute for Genomic Research (TIGR) malaria data base indicate that PfNT1 is a single
copy gene located on chromosome 14. Northern analysis of RNA from
intraerythrocytic stages of the parasite demonstrates that
PfNT1 is expressed throughout the asexual life cycle but is
significantly elevated during the early trophozoite stage. Functional
expression of PfNT1 in Xenopus laevis oocytes
significantly increases their ability to take up naturally occurring
D-adenosine (Km = 13.2 µM) and D-inosine (Km = 253 µM). Significantly, PfNT1, unlike the mammalian nucleoside transporters, also has the capacity to transport the stereoisomer L-adenosine (Km > 500 µM). Inhibition studies with a battery of purine and
pyrimidine nucleosides and bases as well as their analogs indicate that
PfNT1 exhibits a broad substrate specificity for purine and pyrimidine
nucleosides. These data provide compelling evidence that
PfNT1 encodes a functional purine/pyrimidine nucleoside
transporter whose expression is strongly developmentally regulated in
the asexual stages of the P. falciparum life cycle.
Moreover, the unusual ability to transport L-adenosine and
the vital contribution of purine transport to parasite survival makes
PfNT1 an attractive target for therapeutic evaluation.
The nucleotide sequence(s) reported in this paper has been submitted to the GenBankTM/EMBL Data Bank with accession number(s) AF211120, AF211121, and AF211122.
Isolation and Functional Characterization of the PfNT1 Nucleoside
Transporter Gene from Plasmodium falciparum*
,,¶,
**,**
Department of Biochemistry and Molecular
Biology and Department of Molecular Microbiology and Immunology,
Oregon Health Sciences University, Portland, Oregon 97201, § Howard Hughes Medical Institute, Departments of Molecular
Microbiology and Medicine, Washington University School of
Medicine, St. Louis, Missouri 63110, and ¶ Deparment of
Pathology, Federal University of Pará,
Belém, Pará, Brazil
*
This work was supported by National Institutes of Health
Grants AI23682 (to B. U.) and AI44138 (to S. M. L.) and in part by a
grant from the Burroughs Wellcome Fund.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed: Dept. of
Biochemistry and Molecular Biology, Oregon Health Sciences University, Portland, OR 97201. Tel.: 503-494-8437; Fax: 503-494-8393; E-mail: ullmanb@ohsu.edu.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  M. B. Cassera, K. Z. Hazleton, P. M. Riegelhaupt, E. F. Merino, M. Luo, M. H. Akabas, and V. L. Schramm Erythrocytic Adenosine Monophosphate as an Alternative Purine Source in Plasmodium falciparum J. Biol. Chem., November 21, 2008; 283(47): 32889 - 32899. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. J. Downie, K. Kirk, and C. B. Mamoun Purine Salvage Pathways in the Intraerythrocytic Malaria Parasite Plasmodium falciparum Eukaryot. Cell, August 1, 2008; 7(8): 1231 - 1237. [Full Text] [PDF]
|
|
|
|
 |
|
 P. Ellekvist, J. Maciel, G. Mlambo, C. H. Ricke, H. Colding, D. A. Klaerke, and N. Kumar Critical role of a K+ channel in Plasmodium berghei transmission revealed by targeted gene disruption PNAS, April 29, 2008; 105(17): 6398 - 6402. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Valdes, W. Liu, B. Ullman, and S. M. Landfear Comprehensive Examination of Charged Intramembrane Residues in a Nucleoside Transporter J. Biol. Chem., August 11, 2006; 281(32): 22647 - 22655. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. El Bissati, R. Zufferey, W. H. Witola, N. S. Carter, B. Ullman, and C. Ben Mamoun The plasma membrane permease PfNT1 is essential for purine salvage in the human malaria parasite Plasmodium falciparum PNAS, June 13, 2006; 103(24): 9286 - 9291. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L.-M. Ting, W. Shi, A. Lewandowicz, V. Singh, A. Mwakingwe, M. R. Birck, E. A. T. Ringia, G. Bench, D. C. Madrid, P. C. Tyler, et al. Targeting a Novel Plasmodium falciparum Purine Recycling Pathway with Specific Immucillins J. Biol. Chem., March 11, 2005; 280(10): 9547 - 9554. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Chaudhary, J. A. Darling, L. M. Fohl, W. J. Sullivan Jr., R. G. K. Donald, E. R. Pfefferkorn, B. Ullman, and D. S. Roos Purine Salvage Pathways in the Apicomplexan Parasite Toxoplasma gondii J. Biol. Chem., July 23, 2004; 279(30): 31221 - 31227. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. M. Landfear, B. Ullman, N. S. Carter, and M. A. Sanchez Nucleoside and Nucleobase Transporters in Parasitic Protozoa Eukaryot. Cell, April 1, 2004; 3(2): 245 - 254. [Full Text] [PDF]
|
|
|
|
|
|
T. C. Santiago, R. Zufferey, R. S. Mehra, R. A. Coleman, and C. B. Mamoun The Plasmodium falciparum PfGatp is an Endoplasmic Reticulum Membrane Protein Important for the Initial Step of Malarial Glycerolipid Synthesis J. Biol. Chem., March 5, 2004; 279(10): 9222 - 9232. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. N. Al Safarjalani, F. N. M. Naguib, and M. H. el Kouni Uptake of Nitrobenzylthioinosine and Purine {beta}-L-Nucleosides by Intracellular Toxoplasma gondii Antimicrob. Agents Chemother., October 1, 2003; 47(10): 3247 - 3251. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. J. S. Burchmore, L. J. M. Wallace, D. Candlish, M. I. Al-Salabi, P. R. Beal, M. P. Barrett, S. A. Baldwin, and H. P. de Koning Cloning, Heterologous Expression, and in Situ Characterization of the First High Affinity Nucleobase Transporter from a Protozoan J. Biol. Chem., June 20, 2003; 278(26): 23502 - 23507. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Martinussen, S. L. L. Wadskov-Hansen, and K. Hammer Two Nucleoside Uptake Systems in Lactococcus lactis: Competition between Purine Nucleosides and Cytidine Allows for Modulation of Intracellular Nucleotide Pools J. Bacteriol., March 1, 2003; 185(5): 1503 - 1508. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Acimovic and I. R. Coe Molecular Evolution of the Equilibrative Nucleoside Transporter Family: Identification of Novel Family Members in Prokaryotes and Eukaryotes Mol. Biol. Evol., December 1, 2002; 19(12): 2199 - 2210. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Kirk Membrane Transport in the Malaria-Infected Erythrocyte Physiol Rev, April 1, 2001; 81(2): 495 - 537. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. S. Carter, M. E. Drew, M. Sanchez, G. Vasudevan, S. M. Landfear, and B. Ullman Cloning of a Novel Inosine-Guanosine Transporter Gene from Leishmania donovani by Functional Rescue of a Transport-deficient Mutant J. Biol. Chem., June 30, 2000; 275(27): 20935 - 20941. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. A. Kicska, P. C. Tyler, G. B. Evans, R. H. Furneaux, V. L. Schramm, and K. Kim Purine-less Death in Plasmodium falciparum Induced by Immucillin-H, a Transition State Analogue of Purine Nucleoside Phosphorylase J. Biol. Chem., January 25, 2002; 277(5): 3226 - 3231. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Rager, C. B. Mamoun, N. S. Carter, D. E. Goldberg, and B. Ullman Localization of the Plasmodium falciparum PfNT1 Nucleoside Transporter to the Parasite Plasma Membrane J. Biol. Chem., October 26, 2001; 276(44): 41095 - 41099. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Vasudevan, B. Ullman, and S. M. Landfear Point mutations in a nucleoside transporter gene from Leishmania donovani confer drug resistance and alter substrate selectivity PNAS, May 22, 2001; 98(11): 6092 - 6097. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |
