Two novel nucleobase/pentamidine transporters from Trypanosoma brucei

被引:24
作者
Ortiz, Diana [1 ]
Sanchez, Marco A. [1 ]
Quecke, Paula [2 ]
Landfear, Scott M. [1 ]
机构
[1] Oregon Hlth & Sci Univ, Dept Mol Microbiol & Immunol, Portland, OR 97239 USA
[2] Univ Tubingen, Dept Biochem, D-72076 Tubingen, Germany
关键词
African trypanosomes; Nucleobase transporters; Pentamidine; NUCLEOSIDE TRANSPORTER; NUCLEOBASE TRANSPORTER; FUNCTIONAL-CHARACTERIZATION; LEISHMANIA-DONOVANI; PENTAMIDINE UPTAKE; EXPRESSION; GENE; RESISTANCE; ADENOSINE; CLONING;
D O I
10.1016/j.molbiopara.2008.09.011
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
African trypanosomes are unable to synthesize purines de novo, and must salvage preformed purine nucleosides and nucleobases from their hosts. The Trypanosoma brucei genome project has identified 12 members of the equilibrative nucleoside transporter family, most of which have been characterized previously as nucleoside and/or nucleobase transporters. Here the 11 th member of this family, TbNT11.1, has been functionally expressed in null mutants of Leishmania that are deficient in purine nucleoside or nucleobase uptake and identified as a high-affinity purine nucleobase transporter. Expression of TbNT11.1 in Xenopus oocytes revealed that it is also a transporter for the diamidine drug pentamidine that is the principal drug employed to treat early stage human African trypanosomiasis and may thus contribute to the uptake of this therapeutically important compound. In addition, characterization of the 12th member of the family, TbNT12.1, reveals that it is an adenine/pentamidine transporter. (C) 2008 Elsevier B.V. All rights reserved.
引用
收藏
页码:67 / 76
页数:10
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