Cell wall-targeting domain of glycylglycine endopeptidase distinguishes among peptidoglycan cross-bridges
Cell wall-targeting domain of glycylglycine endopeptidase distinguishes among peptidoglycan cross-bridges
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DOI：
10.1074/jbc.m509691200
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发表时间：
2006-01-06
影响因子：
4.8
通讯作者：
Sakon, J
中科院分区：
文献类型：
--
作者：
Lu, JZQ;Fujiwara, T;Sakon, J
ALE-1是溶葡萄球菌酶的同系物，是一种肽聚糖水解酶，通过切割肽聚糖链之间的五甘氨酸键特异性裂解金黄色葡萄球菌细胞壁。ALE-1与S.金黄色葡萄球菌细胞通过其C-末端92个残基，称为靶向结构域，是功能上重要的葡萄球菌溶解活性。ALE-1靶向结构域属于SH 3b结构域家族，是真核SH 3结构域的原核对应物。靶向结构域的1.75埃晶体结构显示出与典型SH 3类似的全β折叠，但具有独特的特征。该结构揭示了邻位靶向结构域之间的保守残基的补丁，形成可以潜在地与革兰氏阳性细胞壁的一些共同特征相互作用的表面区域。采用各种细菌肽聚糖的ALE-1靶向结构域结合研究表明，肽间桥的长度以及肽的氨基酸组成赋予靶向结构域与葡萄球菌肽聚糖的最大结合。高度保守的前9个N-末端残基的截短导致对S的特异性丧失。金黄色葡萄球菌细胞壁靶向，表明这些残基赋予特异性的S。金黄色细胞壁。
ALE-1, a homologue of lysostaphin, is a peptidoglycan hydrolase that specifically lyses Staphylococcus aureus cell walls by cleaving the pentaglycine linkage between the peptidoglycan chains. Binding of ALE-1 to S. aureus cells through its C-terminal 92 residues, known as the targeting domain, is functionally important for staphylolytic activity. The ALE-1-targeting domain belongs to the SH3b domain family, the prokaryotic counterpart of the eukaryotic SH3 domains. The 1.75 angstrom crystal structure of the targeting domain shows an all-beta fold similar to typical SH3s but with unique features. The structure reveals patches of conserved residues among orthologous targeting domains, forming surface regions that can potentially interact with some common features of the Gram-positive cell wall. ALE-1-targeting domain binding studies employing various bacterial peptidoglycans demonstrate that the length of the interpeptide bridge, as well as the amino acid composition of the peptide, confers the maximum binding of the targeting domain to the staphylococcal peptidoglycan. Truncation of the highly conserved first 9 N-terminal residues results in loss of specificity to S. aureus cell wall-targeting, suggesting that these residues confer specificity to S. aureus cell wall.