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作为三锥虫潜在治疗靶点的遗传信息处理途径中的特异性和非同源同功能酶。

Specific and nonhomologous isofunctional enzymes of the genetic information processing pathways as potential therapeutical targets for tritryps.

作者信息

Gomes Monete Rajão, Guimarães Ana Carolina Ramos, de Miranda Antonio Basílio

机构信息

Laboratório de Biologia Computacional e Sistemas, Instituto Oswaldo Cruz/FIOCRUZ, 21045-900 Rio de Janeiro, RJ, Brazil.

出版信息

Enzyme Res. 2011;2011:543912. doi: 10.4061/2011/543912. Epub 2011 Jul 26.

Abstract

Leishmania major, Trypanosoma brucei, and Trypanosoma cruzi (Tritryps) are unicellular protozoa that cause leishmaniasis, sleeping sickness and Chagas' disease, respectively. Most drugs against them were discovered through the screening of large numbers of compounds against whole parasites. Nonhomologous isofunctional enzymes (NISEs) may present good opportunities for the identification of new putative drug targets because, though sharing the same enzymatic activity, they possess different three-dimensional structures thus allowing the development of molecules against one or other isoform. From public data of the Tritryps' genomes, we reconstructed the Genetic Information Processing Pathways (GIPPs). We then used AnEnPi to look for the presence of these enzymes between Homo sapiens and Tritryps, as well as specific enzymes of the parasites. We identified three candidates (ECs 3.1.11.2 and 6.1.1.-) in these pathways that may be further studied as new therapeutic targets for drug development against these parasites.

摘要

硕大利什曼原虫、布氏锥虫和克氏锥虫(三锥虫)是单细胞原生动物,分别引起利什曼病、昏睡病和恰加斯病。大多数针对它们的药物是通过针对完整寄生虫筛选大量化合物而发现的。非同源同功能酶(NISEs)可能为鉴定新的潜在药物靶点提供良好机会,因为尽管它们具有相同的酶活性,但拥有不同的三维结构,从而使得能够开发针对一种或另一种同工型的分子。从三锥虫基因组的公开数据中,我们重建了遗传信息处理途径(GIPPs)。然后我们使用AnEnPi来寻找智人与三锥虫之间这些酶的存在情况,以及寄生虫的特定酶。我们在这些途径中鉴定出了三个候选酶(ECs 3.1.11.2和6.1.1.-),它们可作为针对这些寄生虫的药物开发的新治疗靶点进行进一步研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0263/3145330/5af381e066fb/ER2011-543912.001.jpg

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