title: Structure-based virtual screening to identify the beta-lactamase CTX-M-9 inhibitors: An in silico effort to overcome antibiotic resistance in E. coli.
abstract: Recently, the quick spreads of broad-spectrum beta-lactams antibiotic resistance in pathogenic strains of bacteria have become a major global health problem. These new emerging resistances cause ineffectiveness of antibiotics and increasing the severity of diseases and treatment costs. Among different and diverse resistance targets, we chose a class A beta lactamase, CTX-M-9, with the aim of identifying new chemical entities to be used for further rational drug design. Based on this purpose, a set of 5000 molecules from the Zinc database have been screened by docking experiments using AutoDock Vina software. The best ranked compound, with respect of the previously proved inhibitor compound 19, was further tested by molecular dynamics (MD) simulation. Our molecular modeling analysis demonstrates that ZINC33264777 has ideal characteristics a potent beta lactamase CTX-M-9 inhibitor. In the free form of beta lactamase, NMR relaxation studies showed the extensive motions near the active site and in the Ω-loop. However, our molecular dynamics studies revealed that in the compound 1: beta lactamase complex, the flexibility of Ω-loop was restricted.
authors.affiliation: Department of Microbiology, North Tehran Branch, Islamic Azad University, Tehran, Iran.
authors.forename: Kambiz
authors.initials: K
authors.lastname: Davari
authors.affiliation: Department of Microbiology, North Tehran Branch, Islamic Azad University, Tehran, Iran. Electronic address: nowroozij@yahoo.com.
authors.forename: Jamileh
authors.initials: J
authors.lastname: Nowroozi
authors.affiliation: Department of Microbiology, North Tehran Branch, Islamic Azad University, Tehran, Iran.
authors.forename: Farzaneh
authors.initials: F
authors.lastname: Hosseini
authors.affiliation: Department of Microbiology, North Tehran Branch, Islamic Azad University, Tehran, Iran.
authors.forename: Abbas Akhavan
authors.initials: AA
authors.lastname: Sepahy
authors.affiliation: Department of Biochemistry, Sanandaj Branch, Islamic Azad University, Sanandaj, Iran. Electronic address: sako.biochem@gmail.com.
authors.forename: Sako
authors.initials: S
authors.lastname: Mirzaie
mesh_terms: D001562:Benzimidazoles / Q000737:chemistry*; D004926:Escherichia coli / Q000187:drug effects*; D029968:Escherichia coli Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D011487:Protein Conformation; D013777:Tetrazoles / Q000737:chemistry*; D018440:beta-Lactam Resistance / Q000187:drug effects*; D065093:beta-Lactamase Inhibitors / Q000737:chemistry*; D001618:beta-Lactamases / Q000737:chemistry*
chemical_list: D001562:Benzimidazoles; D029968:Escherichia coli Proteins; D013777:Tetrazoles; D065093:beta-Lactamase Inhibitors; C412613:CTX-M-9 protein, E coli; D001618:beta-Lactamases
keywords: AutoDock vina; Beta lactamase; CTX-M-9; E. coli; Molecular dynamics