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Rv2031c of Mycobacterium tuberculosis: a master regulator of Rv2028–Rv2031 (HspX) operon

机译:结核分枝杆菌Rv2031c:Rv2028–Rv2031(HspX)操纵子的主调节剂

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摘要

Genes belonging to the same operon are transcribed as a single mRNA molecule in all prokaryotes. The genes of the same operon are presumed to be involved in similar metabolic and physiological processes. Hence, computational analysis of constituent proteins could provide important clues to the functional relationships within the operonic genes. This tends to be more fruitful in the case of Mycobacterium tuberculosis (Mtb), considering the number of hypothetical genes with unknown functions and interacting partners. Dramatic advances in the past decade have increased our knowledge of the mechanisms that tubercle bacilli employ to survive within the host. But the phenomenon of Mtb latency continues to baffle all. Rv2031c belonging to dormancy regulon of Mtb is predominantly expressed during latency, with myriad immunological roles. Thus we attempted to analyze the operon comprising Rv2031c protein to gain insights into its role during latency. In the current study, we have carried out computational analysis of proteins encoded by genes known to be a part of this operon. Our study includes phylogenetic analysis, modeling of protein 3D structures, and protein interaction network analysis. We describe the mechanistic role in the establishment of latency and regulation of DevS–DevR component system. Additionally, we have identified the probable role of these proteins in carbohydrate metabolism, erythromycin tolerance, and nucleotide synthesis. Hence, these proteins can modulate the metabolism of Mtb inside the host cells and can be important for its survival in latency. The functional characterization and interactome of this important operon can give insight into its role during latency along with the exploitation of constituent proteins as drug targets and vaccine candidates.
机译:在所有原核生物中,属于同一操纵子的基因被转录为单个mRNA分子。假定相同操纵子的基因参与相似的代谢和生理过程。因此,组成蛋白的计算分析可以为操纵子基因内的功能关系提供重要线索。考虑到功能未知和相互作用伙伴的假设基因的数量,在结核分枝杆菌(Mtb)的情况下,这往往会更有成果。在过去的十年中,戏剧性的进步增加了我们对结核杆菌在宿主体内存活的机制的了解。但是Mtb延迟现象仍然存在。属于Mtb休眠调节子的Rv2031c主要在潜伏期表达,具有多种免疫学作用。因此,我们试图分析包含Rv2031c蛋白的操纵子,以了解其在潜伏期中的作用。在当前的研究中,我们对已知由该操纵子组成的基因编码的蛋白质进行了计算分析。我们的研究包括系统发育分析,蛋白质3D结构建模和蛋白质相互作用网络分析。我们描述了在建立延迟和DevS–DevR组件系统的调节中的机械作用。此外,我们已经确定了这些蛋白质在碳水化合物代谢,红霉素耐受性和核苷酸合成中的可能作用。因此,这些蛋白质可以调节宿主细胞内Mtb的代谢,并且对于其潜伏期的存活很重要。这个重要操纵子的功能表征和相互作用组可以深入了解其在潜伏期中的作用,以及利用构成蛋白质作为药物靶标和疫苗候选物的潜伏期。

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