Eukaryotic protein kinases (ePKs) of the helminth parasite Schistosoma mansoni.
Eukaryotic protein kinases (ePKs) of the helminth parasite Schistosoma mansoni.
复制标题
DOI：
10.1186/1471-2164-12-215
复制
发表时间：
2011-05-06
期刊：
影响因子：
4.4
通讯作者：
Oliveira G
中科院分区：
文献类型：
--
作者：
Andrade LF;Nahum LA;Avelar LG;Silva LL;Zerlotini A;Ruiz JC;Oliveira G
血吸虫病仍然是许多国家的重要寄生虫病和主要经济问题。曼氏血吸虫基因组和预测的蛋白质组序列最近发表，为识别新候选药物提供了机会。真核蛋白激酶 (ePK) 在通过复杂网络介导信号转导中发挥着核心作用，从医学和化学角度来看，被认为是可药物靶标。我们的工作旨在分析曼氏链球菌预测的蛋白质组，以便通过组合计算方法识别和分类该寄生虫的所有 ePK。进行功能注释主要是为了深入了解与其复杂生活方式相关的寄生虫信号传导过程，并选择一些 ePK 作为潜在的药物靶点。通过使用 HMM（隐马尔可夫模型）进行序列相似性搜索，我们已经识别出 252 个 ePK，相当于曼氏酵母预测蛋白质组的 1.9%。与 ePK 保守催化结构域相对应的氨基酸序列通过 MAFFT 进行比对，并进一步用于 PHYLIP 中实施的基于距离的系统发育分析。我们的分析还包括来自其他六种真核生物的 ePK 同源物。结果表明曼氏沙门氏菌在所有 ePK 组中都有蛋白质。根据系统发育分析，它们中的大多数与其他真核生物中已知的 ePK 明显聚集在一起。没有一个 ePK 是曼氏链球菌独有的，也不属于这种寄生虫的一个扩展家族。仅对 16 个曼氏链球菌 ePK 进行了实验研究，预计有 12 种蛋白质没有催化活性，大约 2% 的寄生虫 ePK 仍未分类。一些蛋白质被认为是药物开发的良好靶标，因为它们具有预测的寄生虫的基本功能。我们的方法通过结合相似性和基于系统发育的方法改进了 40% S. mansoni ePK 的功能注释。随着我们继续这项工作，我们将重点关注曼氏链霉菌在寄生虫发育、媒介相互作用和宿主感染过程中对不同环境的生化和生理适应。
Schistosomiasis remains an important parasitic disease and a major economic problem in many countries. The Schistosoma mansoni genome and predicted proteome sequences were recently published providing the opportunity to identify new drug candidates. Eukaryotic protein kinases (ePKs) play a central role in mediating signal transduction through complex networks and are considered druggable targets from the medical and chemical viewpoints. Our work aimed at analyzing the S. mansoni predicted proteome in order to identify and classify all ePKs of this parasite through combined computational approaches. Functional annotation was performed mainly to yield insights into the parasite signaling processes relevant to its complex lifestyle and to select some ePKs as potential drug targets. We have identified 252 ePKs, which corresponds to 1.9% of the S. mansoni predicted proteome, through sequence similarity searches using HMMs (Hidden Markov Models). Amino acid sequences corresponding to the conserved catalytic domain of ePKs were aligned by MAFFT and further used in distance-based phylogenetic analysis as implemented in PHYLIP. Our analysis also included the ePK homologs from six other eukaryotes. The results show that S. mansoni has proteins in all ePK groups. Most of them are clearly clustered with known ePKs in other eukaryotes according to the phylogenetic analysis. None of the ePKs are exclusively found in S. mansoni or belong to an expanded family in this parasite. Only 16 S. mansoni ePKs were experimentally studied, 12 proteins are predicted to be catalytically inactive and approximately 2% of the parasite ePKs remain unclassified. Some proteins were mentioned as good target for drug development since they have a predicted essential function for the parasite. Our approach has improved the functional annotation of 40% of S. mansoni ePKs through combined similarity and phylogenetic-based approaches. As we continue this work, we will highlight the biochemical and physiological adaptations of S. mansoni in response to diverse environments during the parasite development, vector interaction, and host infection.
登录
查看更多内容
DOI：
10.1016/j.bbrc.2006.05.025
发表时间：
2006-07-07
影响因子：
3.1
作者：
Bahia, Diana;Avelar, Livia;Oliveira, Guilherme
通讯作者：
Oliveira, Guilherme
DOI：
10.1590/s0074-02762006000900022
发表时间：
2006-10-01
期刊：
Memórias do Instituto Oswaldo Cruz
影响因子：
--
作者：
Bahia, Diana;Andrade, Luiza Freire;Oliveira, Guilherme
通讯作者：
Oliveira, Guilherme
影响因子：
--
作者：
Donald, RGK;Allocco, J;Liberator, PA
通讯作者：
Liberator, PA
影响因子：
1.5
作者：
Diaz, CA;Allocco, J;Liberator, PA
通讯作者：
Liberator, PA
影响因子：
2.4
作者：
Bahia, D.;Avelar, L. G. A.;Mortara, R. A.
通讯作者：
Mortara, R. A.