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

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• 作者：Jun Min^b ; ¹ ; Da Lin^b ; ¹ ; Qingye Zhang^a ; ^b ; ^{zqy@mail.hzau.edu.cn} ; ^{qingye_zhang2004@yahoo.com.cn} ; Jibing Zhang^b ; Ziniu Yu^b
• 关键词：GlmU ; Inhibitor ; Virtual screening ; Molecular docking ; Biological testing
• 刊名：European Journal of Medicinal Chemistry
• 出版年：2012
• 出版时间：July, 2012
• 年：2012
• 卷：53
• 期：Complete
• 页码：150-158
• 全文大小：968 K

文摘

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 ¦ÌM 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.