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Insertional Tagging, Cloning, and Expression of the Toxoplasma gondii Hypoxanthine-Xanthine-Guanine Phosphoribosyltransferase Gene
The feasibility of HXGPRT as both a positive and negative selectable marker for stable transformation of T. gondii was demonstrated under selection with mycophenolic acid andKinetic analysis of purified recombinant enzyme revealed no significant differences between the two isoforms. Expand
Isolation and Functional Characterization of the PfNT1 Nucleoside Transporter Gene from Plasmodium falciparum *
Evidence is provided 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 and the unusual ability to transport l-adenosine and the vital contribution of purine transport to parasite survival makes Pf NT1 an attractive target for therapeutic evaluation. Expand
Arginase Plays a Pivotal Role in Polyamine Precursor Metabolism in Leishmania
This molecular, biochemical, and genetic dissection of ARG function in L. mexicana promastigotes establishes that the enzyme is essential for parasite viability, that Leishmania, unlike mammalian cells, expresses only one ARG activity, and that the sole vital function of ARg is to provide polyamine precursors for the parasite. Expand
Nucleoside and Nucleobase Transporters in Parasitic Protozoa
One distinctive feature of the biochemistry of parasitic protozoa is their absolute reliance upon the salvage of preformed purines from their vertebrate and invertebrate hosts. While many mammalianExpand
Crystal structures of Toxoplasma gondii adenosine kinase reveal a novel catalytic mechanism and prodrug binding.
The 1.84 A resolution structure of an AK:7-iodotubercidin:AMP-PCP complex reveals the basis for the higher affinity binding of this prodrug over adenosine and thus provides a scaffold for the design of new inhibitors and subversive substrates that target the T. gondii AK. Expand
Multidrug resistance in Leishmania donovani is conferred by amplification of a gene homologous to the mammalian mdr1 gene.
It is demonstrated that amplification of the ldmdr1 gene either by direct selection or subsequent to transfection can confer a drug-resistant phenotype in parasitic protozoa similar to that observed for MDR mammalian cells. Expand
Cloning and structure-function analysis of the Leishmania donovani kinetoplastid membrane protein-11.
Arrangement of the residues located in the putative helical regions on an Edmundson helical wheel showed that this molecule could have a strongly amphipathic conformation and provided an explanation for how such a highly charged protein might be inserted into the plasma membrane. Expand
Mutator phenotypes in mammalian cell mutants with distinct biochemical defects and abnormal deoxyribonucleoside triphosphate pools.
Three mutant murine T-lymphosarcoma cell lines with altered dNTP pools and increased rates of spontaneous mutation are described, which are shown to be characteristic of the cell line and independent of the two genetic markers examined. Expand
Deoxycytidine kinase-mediated toxicity of deoxyadenosine analogs toward malignant human lymphoblasts in vitro and toward murine L1210 leukemia in vivo.
Two deoxynucleosides at concentrations of 3 nM and 0.15 microM inhibited by 50% the growth of human CCRF-CEM malignant lymphoblasts in vitro and had significant chemotherapeutic activity against lymphoid leukemia L1210 in mice. Expand
Ornithine Decarboxylase Gene Deletion Mutants of Leishmania donovani *
The data establish genetically that ODC is an essential gene in L. donovani, define the polyamine requirements of the parasite, and reveal the absence of a polyamine-degradative pathway. Expand