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对广泛蛋白质组进行减法处理,优先考虑假设的 XDR-结核分枝杆菌蛋白作为潜在药物靶标。

Proteome-wide subtractive approach to prioritize a hypothetical protein of XDR-Mycobacterium tuberculosis as potential drug target.

机构信息

Lab 103 PCMD ext. Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, 75270, Pakistan.

National Centre for Bioinformatics, Quaid-i-Azam University, Islamabad, Pakistan.

出版信息

Genes Genomics. 2019 Nov;41(11):1281-1292. doi: 10.1007/s13258-019-00857-z. Epub 2019 Aug 6.

Abstract

BACKGROUND

Among the resistant isolates of MTB, multidrug resistant tuberculosis (MDR-TB) and extensively drug resistant tuberculosis (XDR-TB) have been the areas of growing concern. The genomic analysis showed that the respective genomic pool of the XDR-MTB proteome contains more than 30% of the hypothetical proteins for which no functions have been annotated yet. This class of proteins presumably have their own importance to complete genome and proteome information. The bioinformatics advancements have helped to annotate those hypothetical proteins by using various computational tools and have potential to classify them functionally.

OBJECTIVE

The objective of this study was to propose a new and unique drug target against the deadly Mycobacterium tuberculosis using Bioinformatics approaches to characterize the hypothetical proteins.

RESULTS

We stepwise reduced the hypothetical proteins (total number: 1256) out of the complete proteome to only 26 essential hypothetical proteins. Out of those 26 proteins, the protein WP_003401246.1 was computationally characterized as the druggable target.

CONCLUSION

The study proposed a hypothetical protein from complete proteome of the XDR-MTB as a new drug target against which new drug candidates can be proposed. Hence, the study opens up the new avenues in the areas of drug discovery against deadly M. tuberculosis.

摘要

背景

在耐多药结核分枝杆菌(MTB)的耐药分离株中,耐多药结核病(MDR-TB)和广泛耐药结核病(XDR-TB)已成为日益关注的领域。基因组分析表明,XDR-MTB 蛋白质组的各自基因组库包含超过 30%的假定蛋白质,这些蛋白质尚未被注释功能。这一类蛋白质可能对完整基因组和蛋白质组信息具有自身的重要性。生物信息学的进步已经帮助使用各种计算工具对这些假定蛋白质进行注释,并有可能对它们进行功能分类。

目的

本研究旨在使用生物信息学方法对假定蛋白质进行特征描述,提出针对致命结核分枝杆菌的新的独特药物靶标。

结果

我们逐步从完整蛋白质组中剔除了 1256 个假定蛋白质,仅保留了 26 个必需的假定蛋白质。在这 26 个蛋白质中,蛋白质 WP_003401246.1 被计算为可成药的靶标。

结论

该研究从 XDR-MTB 的完整蛋白质组中提出了一个假定蛋白质作为针对致命结核分枝杆菌的新药物靶标,可以针对该靶标提出新的药物候选物。因此,该研究为针对致命结核分枝杆菌的药物发现开辟了新途径。

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