Mining the Proteome of Fusobacterium nucleatum subsp. nucleatum ATCC 25586 for Potential Therapeutics Discovery: An In Silico Approach.
Mining the Proteome of Fusobacterium nucleatum subsp. nucleatum ATCC 25586 for Potential Therapeutics Discovery: An In Silico Approach.
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DOI：
10.5808/gi.2016.14.4.255
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发表时间：
2016-12
影响因子：
--
通讯作者：
Shahik SM
中科院分区：
文献类型：
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作者：
Habib AM;Islam MS;Sohel M;Mazumder MH;Sikder MO;Shahik SM
近年来，细菌基因组序列信息的大量涌现为抗菌药物的发现带来了许多新的策略，并促进了医学科学应对病原菌对当前抗生素的耐药性不断增加的挑战。本研究采用差减基因组学方法对一株与结直肠癌相关的口腔致病菌具核梭杆菌的全基因组序列进行了分析。我们的研究揭示了F. nucleatum，在人类基因组中没有同源物。通过使用必需基因数据库（DEG）对这些蛋白质进行进一步筛选，鉴定出32种对细菌至关重要的蛋白质。随后使用京都基因和基因组百科全书（KEGG）自动注释服务器（KAAS）对所鉴定的关键蛋白进行分析，结果分选出F.因此，它们可能是作为潜在药物靶点的良好候选者，因为它们对于细菌是独特的，并且在人类中不存在。此外，我们已经证明了这三种蛋白质的三维结构。最后，确定了2个关键蛋白的配体结合位点，并筛选了与配体结合位点最匹配的功能性抑制剂，以期发现有效的新型抗F.核质
The plethora of genome sequence information of bacteria in recent times has ushered in many novel strategies for antibacterial drug discovery and facilitated medical science to take up the challenge of the increasing resistance of pathogenic bacteria to current antibiotics. In this study, we adopted subtractive genomics approach to analyze the whole genome sequence of the Fusobacterium nucleatum, a human oral pathogen having association with colorectal cancer. Our study divulged 1,499 proteins of F. nucleatum, which have no homolog's in human genome. These proteins were subjected to screening further by using the Database of Essential Genes (DEG) that resulted in the identification of 32 vitally important proteins for the bacterium. Subsequent analysis of the identified pivotal proteins, using the Kyoto Encyclopedia of Genes and Genomes (KEGG) Automated Annotation Server (KAAS) resulted in sorting 3 key enzymes of F. nucleatum that may be good candidates as potential drug targets, since they are unique for the bacterium and absent in humans. In addition, we have demonstrated the three dimensional structure of these three proteins. Finally, determination of ligand binding sites of the 2 key proteins as well as screening for functional inhibitors that best fitted with the ligands sites were conducted to discover effective novel therapeutic compounds against F. nucleatum.