Department of Biochemistry, Abdul Wali Khan University Mardan, Mardan-23200, KP, Pakistan.
Department of Zoology, Abdul Wali Khan University Mardan, Mardan-23200, KP, Pakistan.
Curr Top Med Chem. 2019;19(29):2708-2717. doi: 10.2174/1568026619666191105102156.
In the present study, an attempt has been made for subtractive proteomic analysis approach for novel drug targets in Salmonella enterica subsp. enterica serover Typhi str.CT18 using computational tools.
Paralogous, redundant and less than 100 amino acid protein sequences were removed by using CD-HIT. Further detection of bacterial proteins which are non-homologous to host and are essential for the survival of pathogens by using BLASTp against host proteome and DEG`s, respectively. Comparative Metabolic pathways analysis was performed to find unique and common metabolic pathways. The non-redundant, non-homologous and essential proteins were BLAST against approved drug targets for drug targets while Psortb and CELLO were used to predict subcellular localization.
There were 4473 protein sequences present in NCBI Database for Salmonella enterica subsp. enterica serover Typhi str. CT18 out of these 327 were essential proteins which were non-homologous to human. Among these essential proteins, 124 proteins were involved in 19 unique metabolic pathways. These proteins were further BLAST against approved drug targets in which 7 cytoplasmic proteins showed druggability and can be used as a therapeutic target.
Drug targets identification is the prime step towards drug discovery. We identified 7 cytoplasmic druggable proteins which are essential for the pathogen survival and non-homologous to human proteome. Further in vitro and in vivo validation is needed for the evaluation of these targets to combat against salmonellosis.
本研究尝试采用消减蛋白质组学方法,利用计算工具从肠炎沙门氏菌亚种伤寒血清型 CT18 中寻找新型药物靶点。
使用 CD-HIT 去除同源、冗余和小于 100 个氨基酸的蛋白质序列。然后,分别使用 BLASTp 针对宿主蛋白质组和 DEG 检测非宿主同源且对病原体生存至关重要的细菌蛋白。进行比较代谢途径分析以寻找独特和共同的代谢途径。将非冗余、非同源和必需的蛋白质与已批准的药物靶点进行 BLAST 以寻找药物靶点,同时使用 Psortb 和 CELLO 预测亚细胞定位。
在 NCBI 数据库中,有 4473 个序列是肠炎沙门氏菌亚种伤寒血清型 CT18 的蛋白质,其中 327 个是与人类非同源的必需蛋白。在这些必需蛋白中,有 124 种参与了 19 条独特的代谢途径。这些蛋白质进一步与已批准的药物靶点进行 BLAST,其中 7 种细胞质蛋白具有成药性,可以作为治疗靶点。
药物靶点的鉴定是药物发现的首要步骤。我们鉴定了 7 种细胞质可成药性蛋白,它们对病原体的生存至关重要且与人类蛋白质组非同源。需要进一步进行体外和体内验证,以评估这些靶点在对抗沙门氏菌病方面的作用。