Department of Biochemistry, Duke University Medical Center, Durham, North Carolina, USA; email:
Current affiliation: Signature Research Program in Cardiovascular and Metabolic Disorders, Duke-NUS Medical School, Singapore.
Annu Rev Biochem. 2022 Jun 21;91:705-729. doi: 10.1146/annurev-biochem-040320-105145. Epub 2022 Mar 23.
Biosynthesis of many important polysaccharides (including peptidoglycan, lipopolysaccharide, and -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.
许多重要多糖（包括肽聚糖、脂多糖和β-连接聚糖）的生物合成需要将脂连接寡糖（LLO）从其细胞质合成部位转运到其利用部位穿过膜。我们目前对 LLO 转运的大部分了解来自于多药/寡糖脂/多糖（MOP）超家族蛋白 MurJ 的遗传、生化和结构研究，MurJ 翻转肽聚糖前体脂质 II。MurJ 在细菌细胞壁合成中起着至关重要的作用，是一个新兴的抗生素靶标。在这里，我们回顾了 MurJ 翻转 LLO 的机制，包括脂质 II 翻转和离子偶联的结构基础。然后，我们讨论了 MurJ 被抗菌药物的抑制，包括 humimycins 和噬菌体 M 裂解蛋白，以及关于 MurJ 的研究如何为其他翻转酶提供见解，这些酶不仅存在于 MOP 超家族内，也存在于其外。
