SGD Curated Paper 
Luscher A, Onal P, Schweingruber AM, Maser P (2007) Adenosine Kinase of Trypanosoma brucei and Its Role in Susceptibility to Adenosine Antimetabolites. Antimicrob Agents Chemother 51(11):3895-901
Abstract: Trypanosoma brucei cannot synthesize purines de novo and rely on purine salvage from their hosts to build nucleic acids. Adenosine being a preferred purine source of bloodstream-form trypanosomes, adenosine kinase (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 is a tandem gene, expressed in both procyclic and bloodstream-form trypanosomes, whose product localized to the cytosol of the parasites. RNAi-mediated silencing of TbAK suggested that the gene is non-essential under standard growth conditions. Inhibition or down-regulation of TbAK rendered the trypanosomes resistant to cordycepin (3'-deoxyadenosine), demonstrating a role for TbAK in activation of adenosine antimetabolites. Expression of TbAK in yeast complemented a null mutation in the adenosine kinase gene Ado1. Concomitant expression of TbAK with the T. brucei adenosine transporter gene TbAT1 allowed S. cerevisiae ado1/ade2 double mutants to grow on adenosine as sole purine source, and at the same time sensitized them towards adenosine antimetabolites. Co-expression of TbAK and TbAT1 in S. cerevisiae ado1/ade2 double mutants proved to be a convenient tool to test nucleoside analogues for uptake and activation by the T. brucei adenosine salvage enzymes.
| Status: Published | Type: Journal Article | PubMed ID: 17698621 |
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