title: Xanthone derivatives could be potential antibiotics: virtual screening for the inhibitors of enzyme I of bacterial phosphoenolpyruvate-dependent phosphotransferase system.
abstract: The phosphoenolpyruvate phosphotransferase system (PTS) is ubiquitous in eubacteria and absent from eukaryotes. The system consists of two phosphoryl carriers, enzyme I (EI) and the histidine-containing phosphoryl carrier protein (HPr), and several PTS transporters, catalyzing the concomitant uptake and phosphorylation of several carbohydrates. Since a deficiency of EI in bacterial mutants lead to severe growth defects, EI could be a drug target to develop antimicrobial agents. We used the 3D structure PDB 1ZYM of Escherichia coli EI as the target to virtually screen the potential tight binders from NPPEDIA (Natural Product Encyclopedia), ZINC and Super Natural databases. These databases were screened using the docking tools of Discovery Studio 2.0 and the Integrated Drug Design System IDDS. Among the many interesting hits, xanthone derivatives with reasonably high Dock scores received more attentions. Two of the xanthone derivatives were obtained to examine their capabilities to inhibit cell growth of both Gram-positive and Gram-negative bacterial strains. The results indicate that they may exert the inhibition effects by blocking the EI activities. We have demonstrated for the first time that the xanthone derivatives have high potential to be developed as future antibiotics.
authors: Department of Life Science and Institute of Biotechnology, Interdisciplinary Program of Bioinformatics, National Dong Hwa University, Hualien, Taiwan.
authors: Kuo-Jien
authors: KJ
authors: Huang
authors: Shih-Hung
authors: SH
authors: Lin
authors: Meei-Ru
authors: MR
authors: Lin
authors: Hao
authors: H
authors: Ku
authors: Natalia
authors: N
authors: Szkaradek
authors: Henryk
authors: H
authors: Marona
authors: Alvin
authors: A
authors: Hsu
authors: David
authors: D
authors: Shiuan
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D016208:Databases, Factual; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D029968:Escherichia coli Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D062105:Molecular Docking Simulation; D058990:Molecular Targeted Therapy; D010731:Phosphoenolpyruvate Sugar Phosphotransferase System / Q000037:antagonists & inhibitors*; D017852:Phosphotransferases (Nitrogenous Group Acceptor) / Q000037:antagonists & inhibitors*; D044004:Xanthones / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D004791:Enzyme Inhibitors; D029968:Escherichia coli Proteins; D044004:Xanthones; D010731:Phosphoenolpyruvate Sugar Phosphotransferase System; D017852:Phosphotransferases (Nitrogenous Group Acceptor); C022360:phosphoenolpyruvate-protein phosphotransferase