Biosynthesis of many important polysaccharides (including peptidoglycan, lipopolysaccharide, and N-linked glycans) necessitates the transport of lipid-linked oligosaccharides (LLO) across membranes from their cytosolic site of synthesis to their sites of utilization. Much of our current understanding of LLO transport comes from genetic, biochemical, and structural studies of the multidrug/oligosaccharidyl-lipid/polysaccharide (MOP) superfamily protein MurJ, which flips the peptidoglycan precursor lipid II. MurJ plays a pivotal role in bacterial cell wall synthesis and is an emerging antibiotic target. Here, we review the mechanism of LLO flipping by MurJ, including the structural basis for lipid II flipping and ion coupling. We then discuss inhibition of MurJ by antibacterials, including humimycins and the phage M lysis protein, as well as how studies on MurJ could provide insight into other flippases, both within and beyond the MOP superfamily.

中文翻译：

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脂质翻转酶 MurJ 的结构和机制

许多重要多糖（包括肽聚糖、脂多糖和 N 连接聚糖）的生物合成需要脂连接寡糖 (LLO) 跨膜从其胞质合成位点运输至其利用位点。我们目前对 LLO 转运的了解大部分来自对多药/寡糖脂质/多糖 (MOP) 超家族蛋白 MurJ 的遗传、生化和结构研究，该蛋白翻转肽聚糖前体脂质 II。 MurJ 在细菌细胞壁合成中发挥着关键作用，是一个新兴的抗生素靶点。在这里，我们回顾了 MurJ 的 LLO 翻转机制，包括脂质 II 翻转和离子耦合的结构基础。然后，我们讨论了抗菌药物（包括腐殖霉素和噬菌体 M 裂解蛋白）对 MurJ 的抑制，以及对 MurJ 的研究如何能够深入了解 MOP 超家族内外的其他翻转酶。