title: Docking analysis insights quercetin can be a non-antibiotic adjuvant by inhibiting Mmr drug efflux pump in Mycobacterium sp. and its homologue EmrE in Escherichia coli.
abstract: Drug efflux pumps (EP) like Mmr in Mycobacterium transported drugs out of cell, a main reason for drug resistance developing in Mycobacterium tuberculosis. In this in silico study, mainly analysed EP inhibitory potential of a plant-derived flavonoid, quercetin, through docking analysis. Mmr present in Mycobacterium smegmatis and M. tuberculosis, and its homologue EmrE of Escherichia coli was used. Initially, homology modelling of EP monomers and dimers constructed from M. smegmatis, M. tuberculosis and E. coli; the stabilities of models were analysed from Ramachandran plots prepared in PROCHECK. Docking analysis of quercetin with EP protein showed that in all three organisms, the residues for function and stability are important and quercetin had best interactions comparing to compounds such as, verapamil, reserpine, chlorpromazine, Carbonyl Cyanide m- Chloro Phenylhydrazone. Molecular dynamics and simulation studies showed that during the entire course of simulation quercetin-Mmr complex were stable. It insights quercetin can act as a non-antibiotic adjuvant for treatment of tuberculosis by bring down the efflux of drug from bacteria.
authors.affiliation: a Centre for Research on Infectious Diseases , School of Chemical and Biotechnology, SASTRA University , Thanjavur 613401 , India.
authors.forename: Balasubramanian
authors.initials: B
authors.lastname: Suriyanarayanan
authors.forename: Ramachandran
authors.initials: R
authors.lastname: Sarojini Santhosh
mesh_terms: D017920:Antiporters / Q000037:antagonists & inhibitors / Q000737:chemistry*; D004926:Escherichia coli; D029968:Escherichia coli Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry*; D006860:Hydrogen Bonding; D008024:Ligands; D026901:Membrane Transport Proteins / Q000737:chemistry*; D008958:Models, Molecular; D008968:Molecular Conformation; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D009161:Mycobacterium; D011485:Protein Binding; D055503:Protein Multimerization; D021281:Quantitative Structure-Activity Relationship; D011794:Quercetin / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D017920:Antiporters; D029968:Escherichia coli Proteins; D008024:Ligands; D026901:Membrane Transport Proteins; C075436:EmrE protein, E coli; D011794:Quercetin
keywords: Mycobacterium smegmatis; Mycobacterium tuberculosis; efflux pump; quercetin