@article{8770357,
  abstract     = {{Toxoplasma gondii is unable to synthesize purines de novo, instead salvages them from its environment, inside the host cell, for which they need high affinity carriers. Here, we report the expression of a T. gondii Equilibrative Nucleoside Transporter, Tg244440, in a Trypanosoma brucei strain from which nucleobase transporters have been deleted. Tg244440 transported hypoxanthine and guanine with similar affinity (Km ~1 µM), while inosine and guanosine displayed Ki values of 4.05 and 3.30 µM, respectively. Low affinity was observed for adenosine, adenine, and pyrimidines, classifying Tg244440 as a high affinity oxopurine transporter. Purine analogues were used to probe the substrate-transporter binding interactions, culminating in quantitative models showing different binding modes for oxopurine bases, oxopurine nucleosides, and adenosine. Hypoxanthine and guanine interacted through protonated N1 and N9, and through unprotonated N3 and N7 of the purine ring, whereas inosine and guanosine mostly employed the ribose hydroxy groups for binding, in addition to N1H of the nucleobase. Conversely, the ribose moiety of adenosine barely made any contribution to binding. Tg244440 is the first gene identified to encode a high affinity oxopurine transporter in T. gondii and, to the best of our knowledge, the first purine transporter to employ different binding modes for nucleosides and nucleobases.}},
  articleno    = {{710}},
  author       = {{Campagnaro, Gustavo D. and Elati, Hamza A. A. and Balaska, Sofia and Martin Abril, Maria Esther and Natto, Manal J. and Hulpia, Fabian and Lee, Kelly and Sheiner, Lilach and Van Calenbergh, Serge and de Koning, Harry P.}},
  issn         = {{1422-0067}},
  journal      = {{INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES}},
  keywords     = {{Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis,Toxoplasma gondii,purine transporter,Tg244440,nucleobase transporter,apicomplexan,substrate binding,BLOOD-STREAM FORMS,SUBSTRATE RECOGNITION MOTIFS,TRYPANOSOMA-BRUCEI,ADENOSINE KINASE,HIGH-AFFINITY,7-DEAZA-6-BENZYLTHIOINOSINE ANALOGS,6-BENZYLTHIOINOSINE ANALOGS,PYRIMIDINE TRANSPORT,SUBVERSIVE SUBSTRATE,PURINE}},
  language     = {{eng}},
  number       = {{2}},
  pages        = {{19}},
  title        = {{A Toxoplasma gondii oxopurine transporter binds nucleobases and nucleosides using different binding modes}},
  url          = {{http://doi.org/10.3390/ijms23020710}},
  volume       = {{23}},
  year         = {{2022}},
}

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