Structure-based virtual screening of novel inhibitors of the uridyltransferase activity of Xanthomonas oryzae pv. oryzae GlmU

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 IC50 values in the 0.81–23.21 μM range. Subsequently, the mode-of-inhibition and Ki 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.

Graphical abstractThe binding mode of (a) luteolin, (b) hit-19 and (c) hit-25 (shown in stick) in the active site of Xo-GlmU.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► A 3D structure of Xo-GlmU was generated and interaction mechanism was investigated. ► Three hit compounds were identified as specific inhibitors to Xo-GlmU. ► The mode-of-inhibition and Ki values of the three inhibitors were confirmed. ► The MICs of the candidate compounds for Xoo were also determined.