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致病原生动物中的嘌呤和嘧啶转运:从生物学到治疗

Purine and pyrimidine transport in pathogenic protozoa: from biology to therapy.

作者信息

de Koning Harry P, Bridges Daniel J, Burchmore Richard J S

机构信息

Institute of Biomedical and Life Sciences, Division of Infection and Immunity, Joseph Black Building, University of Glasgow, Glasgow G12 8QQ, UK.

出版信息

FEMS Microbiol Rev. 2005 Nov;29(5):987-1020. doi: 10.1016/j.femsre.2005.03.004. Epub 2005 Jul 1.

DOI:10.1016/j.femsre.2005.03.004
PMID:16040150
Abstract

Purine salvage is an essential function for all obligate parasitic protozoa studied to date and most are also capable of efficient uptake of preformed pyrimidines. Much progress has been made in the identification and characterisation of protozoan purine and pyrimidine transporters. While the genes encoding protozoan or metazoan pyrimidine transporters have yet to be identified, numerous purine transporters have now been cloned. All protozoan purine transporter-encoding genes characterised to date have been of the Equilibrative Nucleoside Transporter family conserved in a great variety of eukaryote organisms. However, these protozoan transporters have been shown to be sufficiently different from mammalian transporters to mediate selective uptake of therapeutic agents. Recent studies are increasingly addressing the structure and substrate recognition mechanisms of these vital transport proteins.

摘要

嘌呤补救途径是迄今为止所有已研究的专性寄生原生动物的一项基本功能,并且大多数原生动物还能够高效摄取预先形成的嘧啶。在原生动物嘌呤和嘧啶转运蛋白的鉴定与表征方面已经取得了很大进展。虽然编码原生动物或后生动物嘧啶转运蛋白的基因尚未被鉴定出来,但现在已经克隆了许多嘌呤转运蛋白。迄今为止已表征的所有编码原生动物嘌呤转运蛋白的基因都属于平衡核苷转运蛋白家族,该家族在多种真核生物中保守。然而,这些原生动物转运蛋白已被证明与哺乳动物转运蛋白有足够的差异,能够介导治疗药物的选择性摄取。最近的研究越来越多地关注这些重要转运蛋白的结构和底物识别机制。

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