title: Virtual screening for potential inhibitors of bacterial MurC and MurD ligases.
abstract: Mur ligases are bacterial enzymes involved in the cytoplasmic steps of peptidoglycan biosynthesis and are viable targets for antibacterial drug discovery. We have performed virtual screening for potential ATP-competitive inhibitors targeting MurC and MurD ligases, using a protocol of consecutive hierarchical filters. Selected compounds were evaluated for inhibition of MurC and MurD ligases, and weak inhibitors possessing dual inhibitory activity have been identified. These compounds represent new scaffolds for further optimisation towards multiple Mur ligase inhibitors with improved inhibitory potency.
authors.affiliation: Faculty of Pharmacy, University of Ljubljana, Aškerčeva 7, 1000 Ljubljana, Slovenia.
authors.forename: Tihomir
authors.initials: T
authors.lastname: Tomašić
authors.forename: Andreja
authors.initials: A
authors.lastname: Kovač
authors.forename: Gerhard
authors.initials: G
authors.lastname: Klebe
authors.forename: Didier
authors.initials: D
authors.lastname: Blanot
authors.forename: Stanislav
authors.initials: S
authors.lastname: Gobec
authors.forename: Danijel
authors.initials: D
authors.lastname: Kikelj
authors.forename: Lucija Peterlin
authors.initials: LP
authors.lastname: Mašič
mesh_terms: D000255:Adenosine Triphosphate; D000900:Anti-Bacterial Agents / Q000737:chemistry*; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors*; D001667:Binding, Competitive; D003198:Computer Simulation; D055808:Drug Discovery / Q000379:methods*; D008025:Ligases / Q000037:antagonists & inhibitors*; D010453:Peptide Synthases / Q000037:antagonists & inhibitors
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D000255:Adenosine Triphosphate; D008025:Ligases; D010453:Peptide Synthases; C053379:UDP-N-acetylmuramoylalanine-D-glutamate ligase