Schistosoma mansoni arginase shares functional similarities with human orthologs but depends upon disulphide bridges for enzymatic activity
Schistosoma mansoni arginase shares functional similarities with human orthologs but depends upon disulphide bridges for enzymatic activity
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DOI：
10.1016/j.ijpara.2008.06.015
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发表时间：
2009-02-01
影响因子：
4
通讯作者：
Hesse, Matthias
中科院分区：
文献类型：
--
作者：
Fitzpatrick, Jennifer M.;Fuentes, Jose M.;Hesse, Matthias
在许多热带地区，血吸虫蠕虫对人类健康构成重大威胁。我们首次证明了人类寄生虫曼氏血吸虫的几个发育阶段表达精氨酸酶，该酶负责将L-精氨酸水解为L-鸟氨酸和尿素。在血吸虫病中，由交替激活的巨噬细胞产生的精氨酸酶活性是哺乳动物宿主反应的重要组成部分。然而，以前没有显示寄生虫在与哺乳动物宿主接触时也表达胰蛋白酶。在克隆和测序的cDNA编码的寄生虫酶，我们发现，许多结构特征的人谷胱甘肽转移酶是很好的保守在寄生虫的直系同源物。随后，我们发现S. mansoni酶与两种人源性β-淀粉酶具有许多相似的分子、生化和功能特性，但我们的数据也揭示了人源性β-淀粉酶与人源性β-淀粉酶之间的显著差异。特别是，我们发现的证据表明，与人的双硫酶相比，半胱氨酸的双硫键依赖于溶酶体双硫酶的活性。最后，我们报告S。曼氏酵母菌酶很好地适应于存在于人类宿主中的生理条件。(c)2008年澳大利亚寄生虫学会由爱思唯尔有限公司出版。保留所有权利。
Schistosome helminths constitute a major health risk for the human population in many tropical areas. We demonstrate for the first time that several developmental stages of the human parasite Schistosoma mansoni express arginase, which is responsible for the hydrolysis Of L-arginine to L-ornithine and urea. Arginase activity by alternatively activated macrophages is an essential component of the mammalian host response in schistosomiasis. However, it has not been previously shown that the parasite also expresses arginase when it is in contact with the mammalian host. After cloning and sequencing the cDNA encoding the parasite enzyme, we found that many structural features of human arginase are well conserved in the parasite ortholog. Subsequently, we discovered that S. mansoni arginase shares many similar molecular, biochemical and functional properties with both human arginase isoforms, Nevertheless, our data also reveal striking differences between human and schistosome arginase. Particularly, we found evidence that schistosome arginase activity depends upon disulphide bonds by cysteines, in contrast to human arginase. In conclusion, we report that S. mansoni arginase is well adapted to the physiological conditions that exist in the human host. (c) 2008 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.