Department of Biochemistry and Molecular Biology, Monash University, Clayton 3800, Australia.
Proc Natl Acad Sci U S A. 2012 Jul 31;109(31):12752-7. doi: 10.1073/pnas.1208424109. Epub 2012 Jul 17.
Bacteriophages deploy lysins that degrade the bacterial cell wall and facilitate virus egress from the host. When applied exogenously, these enzymes destroy susceptible microbes and, accordingly, have potential as therapeutic agents. The most potent lysin identified to date is PlyC, an enzyme assembled from two components (PlyCA and PlyCB) that is specific for streptococcal species. Here the structure of the PlyC holoenzyme reveals that a single PlyCA moiety is tethered to a ring-shaped assembly of eight PlyCB molecules. Structure-guided mutagenesis reveals that the bacterial cell wall binding is achieved through a cleft on PlyCB. Unexpectedly, our structural data reveal that PlyCA contains a glycoside hydrolase domain in addition to the previously recognized cysteine, histidine-dependent amidohydrolases/peptidases catalytic domain. The presence of eight cell wall-binding domains together with two catalytic domains may explain the extraordinary potency of the PlyC holoenyzme toward target bacteria.
噬菌体释放溶菌酶，破坏细菌细胞壁，促进病毒从宿主中逸出。当外源性应用时，这些酶可以破坏易感微生物，因此具有作为治疗剂的潜力。迄今为止鉴定出的最有效的溶菌酶是 PlyC，它是一种由两个组件（PlyCA 和 PlyCB）组装而成的酶，对链球菌属具有特异性。本文报道了 PlyC 全酶的结构，揭示了单个 PlyCA 部分与八个 PlyCB 分子组成的环形组装体相连。结构导向的突变分析表明，细菌细胞壁的结合是通过 PlyCB 上的裂缝实现的。出乎意料的是，我们的结构数据显示，PlyCA 除了先前鉴定的半胱氨酸、组氨酸依赖的酰胺水解酶/肽酶催化结构域外，还含有糖苷水解酶结构域。八个细胞壁结合结构域和两个催化结构域的存在可能解释了 PlyC 全酶对靶细菌的非凡效力。
