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Analysis of regulatory protease sequences identified through bioinformatic data mining of the Schistosoma mansoni genome

机译:通过曼氏血吸虫基因组生物信息学数据挖掘鉴定的调控蛋白酶序列的分析

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Background New chemotherapeutic agents against Schistosoma mansoni, an etiological agent of human schistosomiasis, are a priority due to the emerging drug resistance and the inability of current drug treatments to prevent reinfection. Proteases have been under scrutiny as targets of immunological or chemotherapeutic anti-Schistosoma agents because of their vital role in many stages of the parasitic life cycle. Function has been established for only a handful of identified S. mansoni proteases, and the vast majority of these are the digestive proteases; very few of the conserved classes of regulatory proteases have been identified from Schistosoma species, despite their vital role in numerous cellular processes. To that end, we identified protease protein coding genes from the S. mansoni genome project and EST library. Results We identified 255 protease sequences from five catalytic classes using predicted proteins of the S. mansoni genome. The vast majority of these show significant similarity to proteins in KEGG and the Conserved Domain Database. Proteases include calpains, caspases, cytosolic and mitochondrial signal peptidases, proteases that interact with ubiquitin and ubiquitin-like molecules, and proteases that perform regulated intramembrane proteolysis. Comparative analysis of classes of important regulatory proteases find conserved active site domains, and where appropriate, signal peptides and transmembrane helices. Phylogenetic analysis provides support for inferring functional divergence among regulatory aspartic, cysteine, and serine proteases. Conclusion Numerous proteases are identified for the first time in S. mansoni. We characterized important regulatory proteases and focus analysis on these proteases to complement the growing knowledge base of digestive proteases. This work provides a foundation for expanding knowledge of proteases in Schistosoma species and examining their diverse function and potential as targets for new chemotherapies.
机译:背景技术由于出现的耐药性和当前药物治疗无法预防再感染,针对人类血吸虫病的病原体曼氏血吸虫的新化学治疗剂是优先考虑的。由于蛋白酶在寄生虫生命周期的许多阶段都起着至关重要的作用,因此它们一直被作为免疫或化学治疗抗血吸虫病药物的靶标进行审查。仅对少数已鉴定的曼氏沙门氏菌(S.mansoni)蛋白酶建立了功能,其中绝大多数是消化蛋白酶。尽管血吸虫在许多细胞过程中起着至关重要的作用,但从血吸虫物种中已鉴定出很少的保守调节蛋白酶。为此,我们从曼氏葡萄球菌基因组计划和EST文库中鉴定了蛋白酶蛋白编码基因。结果我们使用曼氏链球菌基因组的预测蛋白从五个催化类别中鉴定了255个蛋白酶序列。其中绝大多数显示出与KEGG和保守域数据库中的蛋白质非常相似。蛋白酶包括钙蛋白酶,半胱氨酸蛋白酶,胞质和线粒体信号肽酶,与泛素和泛素样分子相互作用的蛋白酶,以及执行调节性膜内蛋白水解的蛋白酶。对重要调节蛋白酶类别的比较分析发现了保守的活性位点域,并在适当的情况下发现了信号肽和跨膜螺旋。系统发育分析为推断调节天冬氨酸,半胱氨酸和丝氨酸蛋白酶之间的功能差异提供了支持。结论曼氏沙门氏菌首次鉴定出多种蛋白酶。我们表征了重要的调节性蛋白酶,并对这些蛋白酶进行了重点分析,以补充消化蛋白酶不断增长的知识基础。这项工作为扩大血吸虫物种中的蛋白酶的知识和检查其多样化的功能和作为新化学疗法靶标的潜力提供了基础。

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