Bugg Timothy D H, Lloyd Adrian J, Roper David I
Department of Chemistry, University of Warwick, Coventry CV4 7AL, UK.
Infect Disord Drug Targets. 2006 Jun;6(2):85-106. doi: 10.2174/187152606784112128.
Phospho-MurNAc-pentapeptide translocase (MraY, translocase I) catalyses the first step of the lipid-linked cycle of reactions of bacterial peptidoglycan biosynthesis. MraY is the target for five families of nucleoside antibacterial natural products: the tunicamycins, the mureidomycins (also pacidamycins, napsamycins), the liposidomycins, the muraymycins, and the capuramycins. Recent structure-activity studies on these families have led to the identification of active pharmacophores, and insight into their mechanisms of action. This step of peptidoglycan biosynthesis is also the target for the bacteriolytic E protein from bacteriophage phiX174, and for cyclic peptides of the amphomycin family which complex the undecaprenyl phosphate co-substrate. The mechanisms of enzyme inhibition by these agents are discussed, and the state of knowledge regarding the transmembrane structure, active site, and catalytic mechanism of MraY. The availability of high throughput assays and prospects of MraY as an antibacterial target are also discussed.
磷酸化的胞壁酰五肽转位酶（MraY，转位酶I）催化细菌肽聚糖生物合成的脂质连接反应循环的第一步。MraY是五类核苷类抗菌天然产物的作用靶点：衣霉素、多氧霉素（也包括巴西霉素、纳普霉素）、脂霉素、穆雷霉素和卡普拉霉素。最近对这些家族的构效关系研究已鉴定出活性药效团，并深入了解了它们的作用机制。肽聚糖生物合成的这一步也是噬菌体phiX174的溶菌E蛋白以及与十一异戊烯磷酸共底物结合的两性霉素家族环肽的作用靶点。讨论了这些试剂对酶的抑制机制，以及关于MraY跨膜结构、活性位点和催化机制的知识现状。还讨论了高通量检测方法的可用性以及MraY作为抗菌靶点的前景。
