title: Structure-based virtual screening of novel inhibitors of the uridyltransferase activity of Xanthomonas oryzae pv. oryzae GlmU.
abstract: N-Acetylglucosamine-1-phosphate uridyltransferase (GlmU) catalyzes the formation of UDP-GlcNAc, a fundamental precursor in cell wall biosynthesis. GlmU represents an attractive target for new antibacterial agents. In this study, a theoretical three-dimensional (3D) structure of GlmU from Xanthomonas oryzae pv. oryzae (Xo-GlmU) was generated, and the ligand-receptor interaction was investigated by molecular docking. Then a structure-based virtual screening was performed, three hit compounds were identified as specific inhibitors of the uridyltransferase activity of Xo-GlmU, with IC(50) values in the 0.81-23.21 μM range. Subsequently, the mode-of-inhibition and K(i) values of the three inhibitors were confirmed. The minimum inhibitory concentrations (MICs) of the candidate compounds for X. oryzae pv. oryzae (Xoo) were also determined. The research provided novel chemical scaffolds for antimicrobial drug discovery.
authors.affiliation: State Key Laboratory of Agricultural Microbiology, National Engineering Research Centre of Microbial Pesticides, Huazhong Agricultural University, Wuhan 430070, PR China.
authors.forename: Jun
authors.initials: J
authors.lastname: Min
authors.forename: Da
authors.initials: D
authors.lastname: Lin
authors.forename: Qingye
authors.initials: Q
authors.lastname: Zhang
authors.forename: Jibing
authors.initials: J
authors.lastname: Zhang
authors.forename: Ziniu
authors.initials: Z
authors.lastname: Yu
mesh_terms: D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid; D006599:UDPglucose-Hexose-1-Phosphate Uridylyltransferase / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D014584:User-Computer Interface; D014974:Xanthomonas / Q000187:drug effects / Q000201:enzymology*
chemical_list: D004791:Enzyme Inhibitors; D006599:UDPglucose-Hexose-1-Phosphate Uridylyltransferase