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Bioinformatic analysis of beta carbonic anhydrase sequences from protozoans and metazoans

机译:来自原生动物和后生动物的β碳酸酐酶序列的生物信息学分析

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摘要

BackgroundDespite the high prevalence of parasitic infections, and their impact on global health and economy, the number of drugs available to treat them is extremely limited. As a result, the potential consequences of large-scale resistance to any existing drugs are a major concern. A number of recent investigations have focused on the effects of potential chemical inhibitors on bacterial and fungal carbonic anhydrases. Among the five classes of carbonic anhydrases (alpha, beta, gamma, delta and zeta), beta carbonic anhydrases have been reported in most species of bacteria, yeasts, algae, plants, and particular invertebrates (nematodes and insects). To date, there has been a lack of knowledge on the expression and molecular structure of beta carbonic anhydrases in metazoan (nematodes and arthropods) and protozoan species.MethodsHere, the identification of novel beta carbonic anhydrases was based on the presence of the highly-conserved amino acid sequence patterns of the active site. A phylogenetic tree was constructed based on codon-aligned DNA sequences. Subcellular localization prediction for each identified invertebrate beta carbonic anhydrase was performed using the TargetP webserver.ResultsWe verified a total of 75 beta carbonic anhydrase sequences in metazoan and protozoan species by proteome-wide searches and multiple sequence alignment. Of these, 52 were novel, and contained highly conserved amino acid residues, which are inferred to form the active site in beta carbonic anhydrases. Mitochondrial targeting peptide analysis revealed that 31 enzymes are predicted with mitochondrial localization; one was predicted to be a secretory enzyme, and the other 43 were predicted to have other undefined cellular localizations.ConclusionsThese investigations identified 75 beta carbonic anhydrases in metazoan and protozoan species, and among them there were 52 novel sequences that were not previously annotated as beta carbonic anhydrases. Our results will not only change the current information in proteomics and genomics databases, but will also suggest novel targets for drugs against parasites.
机译:背景技术尽管寄生虫感染的流行率很高,并且对全球健康和经济产生影响,但可用于治疗它们的药物数量却极为有限。结果,对任何现有药物的大规模耐药性的潜在后果是一个主要问题。最近的许多研究集中于潜在的化学抑制剂对细菌和真菌碳酸酐酶的影响。在五种碳酸酐酶(α,β,γ,δ和zeta)中,β碳酸酐酶已在大多数细菌,酵母,藻类,植物特别是无脊椎动物(线虫和昆虫)中报道。迄今为止,对后生动物(线虫和节肢动物)和原生动物物种中β碳酸酐酶的表达和分子结构缺乏了解。方法在此,基于高度保守的β-碳酸酐酶的鉴定活性位点的氨基酸序列模式。基于密码子比对的DNA序列构建了系统树。使用TargetP Web服务器对每个鉴定出的无脊椎动物β碳酸酐酶进行亚细胞定位预测。结果我们通过蛋白质组范围内的搜索和多个序列比对,验证了后生动物和原生动物物种中总共75个β碳酸酐酶序列。其中52个是新的,并包含高度保守的氨基酸残基,据推测这些残基在β碳酸酐酶中形成了活性位点。线粒体靶向肽分析显示,线粒体定位可预测31种酶。结论这些研究在后生动物和原生动物物种中鉴定出75种β-碳酸酐酶,其中52种新的序列先前未标注为β。碳酸酐酶。我们的结果不仅会改变蛋白质组学和基因组学数据库中的当前信息,还将为抗寄生虫药物提出新的靶标。

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