ArticleAntimicrobial agents and chemotherapy2007
Adenosine kinase of Trypanosoma brucei and its role in susceptibility to adenosine antimetabolites.
Article in Antimicrobial agents and chemotherapy, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 36 citations in OpenAlex.
- Acyclic nucleoside phosphonates with adenine nucleobase inhibit Trypanosoma brucei adenine phosphoribosyltransferase in vitro.Scientific reports · 2021Article
- 4E Interacting Protein as a Potential Novel Drug Target for Nucleoside Analogues inMicroorganisms · 2021Article
- Differentially Expressed Homologous Genes Reveal Interspecies Differences ofHelminthologia · 2020Article
- Combining tubercidin and cordycepin scaffolds results in highly active candidates to treat late-stage sleeping sickness.Nature communications · 2019Article
- Functional and genetic evidence that nucleoside transport is highly conserved in Leishmania species: Implications for pyrimidine-based chemotherapy.International journal for parasitology. Drugs and drug resistance · 2017Article
- 9-(2'-Deoxy-2'-Fluoro-β-d-Arabinofuranosyl) Adenine Is a Potent Antitrypanosomal Adenosine Analogue That Circumvents Transport-Related Drug Resistance.Antimicrobial agents and chemotherapy · 2017Article
- Novel Characteristics of Trypanosoma brucei Guanosine 5'-monophosphate Reductase Distinct from Host Animals.PLoS neglected tropical diseases · 2016Article
- An Atypical Mitochondrial Carrier That Mediates Drug Action in Trypanosoma brucei.PLoS pathogens · 2015Article
- Trypanosoma brucei adenine-phosphoribosyltransferases mediate adenine salvage and aminopurinol susceptibility but not adenine toxicity.International journal for parasitology. Drugs and drug resistance · 2014Article
- Adenosine kinase: exploitation for therapeutic gain.Pharmacological reviews · 2013Review
- Pyrimidine salvage in Trypanosoma brucei bloodstream forms and the trypanocidal action of halogenated pyrimidines.Molecular pharmacology · 2013Article
- Trypanosoma brucei thymidine kinase is tandem protein consisting of two homologous parts, which together enable efficient substrate binding.The Journal of biological chemistry · 2012Article
- In-silico investigation of antitrypanosomal phytochemicals from Nigerian medicinal plants.PLoS neglected tropical diseases · 2012Article
- State of the art in African trypanosome drug discovery.Current topics in medicinal chemistry · 2011Review
- Inhibitors of adenosine consuming parasites through polymer-assisted N-acylation of N6-substituted 5'-amino-5'-deoxyadenosines.Molecular diversity · 2010Article
- Evaluation of nucleoside hydrolase inhibitors for treatment of African trypanosomiasis.Antimicrobial agents and chemotherapy · 2010Article
- Adenosine Kinase of T. b. Rhodesiense identified as the putative target of 4-[5-(4-phenoxyphenyl)-2H-pyrazol-3-yl]morpholine using chemical proteomics.PLoS neglected tropical diseases · 2009Article
- Preclinical assessment of the treatment of second-stage African trypanosomiasis with cordycepin and deoxycoformycin.PLoS neglected tropical diseases · 2009Article
- An adenosine kinase exists in Xanthomonas campestris pathovar campestris and is involved in extracellular polysaccharide production, cell motility, and virulence.Journal of bacteriology · 2009Article
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4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Trypanosoma brucei cannot synthesize purines de novo and relies on purine salvage from its hosts to build nucleic acids. With adenosine being a preferred purine source of bloodstream-form trypanosomes, adenosine kinase (AK; EC 2.7.1.20) is likely to be a key player in purine salvage. Adenosine kinase is also of high pharmacological interest, since for many adenosine antimetabolites, phosphorylation is a prerequisite for activity. Here, we cloned and functionally characterized adenosine kinase from T. brucei (TbAK). TbAK is a tandem gene, expressed in both procyclic- and bloodstream-form trypanosomes, whose product localized to the cytosol of the parasites. The RNA interference-mediated silencing of TbAK suggested that the gene is nonessential under standard growth conditions. Inhibition or downregulation of TbAK rendered the trypanosomes resistant to cordycepin (3'-deoxyadenosine), demonstrating a role for TbAK in the activation of adenosine antimetabolites. The expression of TbAK in Saccharomyces cerevisiae complemented a null mutation in the adenosine kinase gene ado1. The concomitant expression of TbAK with the T. brucei adenosine transporter gene TbAT1 allowed S. cerevisiae ado1 ade2 double mutants to grow on adenosine as the sole purine source and, at the same time, sensitized them to adenosine antimetabolites. The coexpression of TbAK and TbAT1 in S. cerevisiae ado1 ade2 double mutants proved to be a convenient tool for testing nucleoside analogues for uptake and activation by T. brucei adenosine salvage enzymes.
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