The rapid growth of antibiotic-resistant bacterial infections is of major concern for human health. Therefore, it is of great importance to characterize novel targets for the development of antibacterial drugs. One promising protein target is MraY (UDP-N-acetylmuramyl-pentapeptide: undecaprenyl phosphate N-acetylmuramyl-pentapeptide-1-phosphate transferase or MurNAc-1-P-transferase), which is essential for bacterial cell wall synthesis. Here, we summarize recent breakthroughs in structural studies of bacterial MraYs and the closely related human GPT (UDP-N-acetylglucosamine: dolichyl phosphate N-acetylglucosamine-1-phosphate transferase or GlcNAc-1-P-transferase). We present a detailed comparison of interaction modes with the natural product inhibitors tunicamycin and muraymycin D2. Finally, we speculate on possible routes to design an antibacterial agent in the form of a potent and selective inhibitor against MraY.

耐抗生素细菌感染的快速增长是人类健康的主要问题。因此，表征抗菌药物开发的新靶标非常重要。一种有前途的蛋白质靶标是MraY（UDP- N-乙酰村酰-五肽：十一碳烯基磷酸N-乙酰村酰-五肽-1-磷酸转移酶或MurNAc-1-P-转移酶），它对于细菌细胞壁的合成是必不可少的。在这里，我们总结了细菌MraYs和与之密切相关的人类GPT（UDP- N-乙酰氨基葡萄糖：磷酸二氢吡啶酯N）的结构研究中的最新突破。-乙酰基氨基葡萄糖-1-磷酸转移酶或GlcNAc-1-P-转移酶）。我们提出了与天然产物抑制剂衣霉素和穆拉霉素D2相互作用模式的详细比较。最后，我们推测了可能的方法，以设计一种有效且选择性的针对MraY的抑制剂形式的抗菌剂。