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利用计算分析确定社区获得性耐甲氧西林金黄色葡萄球菌(CA-MRSA)潜在的治疗药物靶点

Potential therapeutic drug target identification in Community Acquired-Methicillin Resistant Staphylococcus aureus (CA-MRSA) using computational analysis.

作者信息

Yadav Pramod Kumar, Singh Gurmit, Singh Satendra, Gautam Budhayash, Saad Esmaiel If

机构信息

Department of Computational Biology & Bioinformatics, JSBB, SHIATS (DU), Allahabad-211007, India.

出版信息

Bioinformation. 2012;8(14):664-72. doi: 10.6026/97320630008664. Epub 2012 Jul 21.

Abstract

The emergence of multidrug-resistant strain of community-acquired methicillin resistant Staphylococcus aureus (CA-MRSA) strain has highlighted the urgent need for the alternative and effective therapeutic approach to combat the menace of this nosocomial pathogen. In the present work novel potential therapeutic drug targets have been identified through the metabolic pathways analysis. All the gene products involved in different metabolic pathways of CA-MRSA in KEGG database were searched against the proteome of Homo sapiens using the BLASTp program and the threshold of E-value was set to as 0.001. After database searching, 152 putative targets were identified. Among all 152 putative targets, 39 genes encoding for putative targets were identified as the essential genes from the DEG database which are indispensable for the survival of CA-MRSA. After extensive literature review, 7 targets were identified as potential therapeutic drug target. These targets are Fructose-bisphosphate aldolase, Phosphoglyceromutase, Purine nucleoside phosphorylase, Uridylate kinase, Tryptophan synthase subunit beta, Acetate kinase and UDP-N-acetylglucosamine 1-carboxyvinyltransferase. Except Uridylate kinase all the identified targets were involved in more than one metabolic pathways of CA-MRSA which underlines the importance of drug targets. These potential therapeutic drug targets can be exploited for the discovery of novel inhibitors for CA-MRSA using the structure based drug design (SBDD) strategy.

摘要

社区获得性耐甲氧西林金黄色葡萄球菌(CA-MRSA)多药耐药菌株的出现凸显了对抗这种医院病原体威胁的替代有效治疗方法的迫切需求。在本研究中,通过代谢途径分析确定了新的潜在治疗药物靶点。使用BLASTp程序在KEGG数据库中搜索参与CA-MRSA不同代谢途径的所有基因产物,并将E值阈值设置为0.001,以人类蛋白质组进行比对。数据库搜索后,确定了152个推定靶点。在所有152个推定靶点中,从DEG数据库中鉴定出39个编码推定靶点的基因是CA-MRSA生存所必需的必需基因。经过广泛的文献综述,确定了7个潜在治疗药物靶点。这些靶点是果糖-1,6-二磷酸醛缩酶、磷酸甘油变位酶、嘌呤核苷磷酸化酶、尿苷酸激酶、色氨酸合酶β亚基、乙酸激酶和UDP-N-乙酰葡糖胺1-羧乙烯基转移酶。除尿苷酸激酶外,所有鉴定出的靶点都参与了CA-MRSA的多个代谢途径,这突出了药物靶点的重要性。这些潜在治疗药物靶点可利用基于结构的药物设计(SBDD)策略来发现针对CA-MRSA的新型抑制剂。

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