title: Targeting essential cell wall lipase Rv3802c for potential therapeutics against tuberculosis.
abstract: 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 -3.28kcal/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.
authors.affiliation: Department of Biotechnology, Indian Institute of Technology Guwahati, Guwahati 781039, Assam, India.
authors.forename: Parameswaran
authors.initials: P
authors.lastname: Saravanan
authors.forename: Hindupur
authors.initials: H
authors.lastname: Avinash
authors.forename: Vikash Kumar
authors.initials: VK
authors.lastname: Dubey
authors.forename: Sanjukta
authors.initials: S
authors.lastname: Patra
mesh_terms: D000595:Amino Acid Sequence; D000995:Antitubercular Agents / Q000737:chemistry*; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry*; D001665:Binding Sites; D002473:Cell Wall / Q000737:chemistry* / Q000201:enzymology; D015195:Drug Design; D006801:Humans; D006860:Hydrogen Bonding; D007700:Kinetics; D008049:Lipase / Q000037:antagonists & inhibitors / Q000737:chemistry*; D050356:Lipid Metabolism; D062105:Molecular Docking Simulation; D008969:Molecular Sequence Data; D058990:Molecular Targeted Therapy; D009169:Mycobacterium tuberculosis / Q000737:chemistry* / Q000201:enzymology; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D055672:Static Electricity; D013816:Thermodynamics
chemical_list: D000995:Antitubercular Agents; D001426:Bacterial Proteins; D008049:Lipase