Structural basis for selective recognition of pneumococcal cell wall by modular endolysin from phage Cp-1
Structural basis for selective recognition of pneumococcal cell wall by modular endolysin from phage Cp-1
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DOI：
10.1016/j.str.2003.09.005
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发表时间：
2003-10-01
期刊：
影响因子：
5.7
通讯作者：
Menéndez, M
中科院分区：
文献类型：
--
作者：
Hermoso, JA;Monterroso, B;Menéndez, M
肺炎球菌噬菌体编码的溶酶素是模块化胆碱结合蛋白，已被证明可作为抗链球菌感染的酶促抗菌剂（酶制剂）。在这里，我们展示了肺炎球菌噬菌体Cp-1编码的CpI-1溶酶的游离态和胆碱结合态的晶体结构。催化模块呈现不规则的（β / α）(5) β(3)桶状结构，细胞壁锚定模块由六个相似的胆碱结合重复序列（ChBrs）组成，排列在两个不同的结构区域：一个左旋超螺旋结构域配置两个胆碱结合位点，一个β片结构域将整个结构聚集在一起。晶体学和定点诱变研究使我们能够提出整个糖苷水解酶家族的一般催化机制25。我们的工作首次提供了胆碱结合蛋白大家族成员的完整结构，并揭示了chbr是能够调节肺炎球菌表面蛋白的进化和特异性的通用元件。
Pneumococcal bacteriophage-encoded lysins are modular choline binding proteins that have been shown to act as enzymatic antimicrobial agents (enzybiotics) against streptococcal infections. Here we present the crystal structures of the free and choline bound states of the CpI-1 lysin, encoded by the pneumococcal phage Cp-1. While the catalytic module displays an irregular (beta/alpha)(5)beta(3) barrel, the cell wall-anchoring module is formed by six similar choline binding repeats (ChBrs), arranged into two different structural regions: a left-handed superhelical domain configuring two choline binding sites, and a beta sheet domain that contributes in bringing together the whole structure. Crystallographic and site-directed mutagenesis studies allow us to propose a general catalytic mechanism for the whole glycoside hydrolase family 25. Our work provides the first complete structure of a member of the large family of choline binding proteins and reveals that ChBrs are versatile elements able to tune the evolution and specificity of the pneumococcal surface proteins.