Gene network analysis of Aeromonas hydrophila for novel drug target discovery.

Systems and Synthetic Biology Pub Date : 2012-06-01 Epub Date: 2012-05-22 DOI:10.1007/s11693-012-9093-z
Vijai Singh, Dharmendra Kumar Chaudhary, Indra Mani
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引用次数: 4

Abstract

Increasing the multi-drug resistance Aeromonas hydrophila creates a health problem regularly thus, an urgent needs to develop and screen potent antibiotics for controlling of the infections. There are many studies have focused on interactions between specific drugs, little is known about the system properties of a full drug interaction in gene network. Thus, an attractive approach for developing novel antibiotics against DNA gyrase, an enzyme essential for DNA replication, transcription, repair and recombination mechanisms which is important for bacterial growth and cell division. Homology modeling method was used to generate the 3-D structure of B subunit of DNA gyrase (gyrB) using known crystal structure. The active amino acids in 3-D structure of gyrB were targeted for structure based virtual screening of potent drugs by molecular docking. Number of drugs and analogs were selected and used for docking against gryB. The drugs Cinodine I, Cyclothialidine and Novobiocin were found to be more binding affinity with gyrB-drug interaction. The homology of gyrB protein sequence of A. hydrophila resembles with other species of Aeromonas closely showed relationship in phylogenetic tree. We have also demonstrated the gene network interactions of gyrB with other cellular proteins which are playing the key role in gene regulation. These findings provide new insight to understand the 3-D structure of gyrB which can be used in structure-based drug discovery; and development of novel, potent and specific drug against B subunit of DNA gyrase.

嗜水气单胞菌基因网络分析用于新药靶点发现。
耐多药嗜水气单胞菌的增加经常造成健康问题,因此迫切需要开发和筛选有效的抗生素来控制感染。许多研究集中在特定药物之间的相互作用,但对基因网络中药物相互作用的系统特性知之甚少。DNA回转酶是一种对细菌生长和细胞分裂至关重要的DNA复制、转录、修复和重组机制至关重要的酶,因此,开发新型抗生素是一种有吸引力的方法。利用已知的晶体结构,采用同源性建模方法生成DNA旋切酶(gyrB) B亚基的三维结构。以gyrB三维结构中的活性氨基酸为靶点,通过分子对接进行基于结构的强效药物虚拟筛选。选择若干药物和类似物用于对接对抗gryB。Cinodine I、Cyclothialidine和Novobiocin等药物与gyrB-drug相互作用的结合亲和力更强。在系统进化树中,嗜水单胞菌gyrB蛋白序列的同源性与其他气单胞菌相似。我们还证明了gyrB与其他细胞蛋白的基因网络相互作用,这些蛋白在基因调控中起着关键作用。这些发现为了解gyrB的三维结构提供了新的视角,可用于基于结构的药物发现;以及针对DNA回转酶B亚基的新型、强效和特异性药物的开发。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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