Targeting essential cell wall lipase Rv3802c for potential therapeutics against tuberculosis

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• 作者：Parameswaran Saravanan ; Hindupur Avinash ; Vikash Kumar Dubey ; Sanjukta Patra ; ^{sanjukta@iitg.ernet.in}
• 关键词：Rv3802c ; Tuberculosis ; Lipase ; Cell wall ; Lipid metabolism ; Homology modelling ; Virtual screening
• 刊名：Journal of Molecular Graphics and Modelling
• 出版年：2012
• 出版时间：September, 2012
• 年：2012
• 卷：38
• 期：Complete
• 页码：235-242
• 全文大小：1563 K

文摘

Cell wall and lipid metabolism plays a vital role in the survival and infection of Mycobacterium tuberculosis. Increase in the incidences of life-threatening multidrug-resistant (MDR) and extreme drug-resistant (XDR) tuberculosis worsens the existing scenario and urge the need of new druggable targets and new drugs. Targeting Rv3802c, an essential cell wall lipase, can open up a new arsenal to fight the dreadful opportunistic pathogen. Our current study highlights the essentiality of Rv3802c. Its 3D structure is predicted for the first time which provides insight in identifying the ligand binding sites. Our analysis showed Rv3802c is highly conserved throughout mycobacterial species with no significant sequence homolog found in human proteome. Virtual screening followed by comparative docking studies of Rv3802c with its closest human structural homolog has been carried out to identify potential inhibitors effective towards mycobacterial proteins. Two diverse molecules from ZINC database, ZINC26726377 and ZINC43866786 have been identified as potential inhibitors effective towards Rv3802c based on the difference in predicted binding free energy of ?3.99 and ?3.28 kcal/mol respectively. Rv3802c is a promising drug target and also a step towards understanding and targeting the pathogen's cell wall and lipid metabolism simultaneously to combat tuberculosis.