DOUGHNUT-SHAPED STRUCTURE OF A BACTERIAL MURAMIDASE REVEALED BY X-RAY CRYSTALLOGRAPHY
DOUGHNUT-SHAPED STRUCTURE OF A BACTERIAL MURAMIDASE REVEALED BY X-RAY CRYSTALLOGRAPHY
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DOI：
10.1038/367750a0
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发表时间：
1994-02-24
期刊：
影响因子：
64.8
通讯作者：
DIJKSTRA, BW
中科院分区：
文献类型：
--
作者：
THUNNISSEN, AMWH;DIJKSTRA, AJ;DIJKSTRA, BW
细菌细胞壁的完整性取决于几种肽聚糖（蛋白）合成和降解酶的平衡作用1,2。青霉素抑制肽聚糖聚合体中负责肽交联的酶3。仅作用于糖苷键的酶对这种抗生素不敏感，因此为设计与β -内酰胺不同的抗生素提供了一个目标。在这里，我们报告了来自大肠杆菌的质周可溶性裂解转糖基化酶（SLT； M(r) 70000）的x射线结构。这种独特的细菌外胞酰胺酶可切割肽聚糖的-1,4-糖苷键，产生小的1,6-无水多肽4-6。SLT的结构揭示了一个“超螺旋”的α螺旋环，顶部有一个独立的结构域，类似于溶菌酶的折叠。位点定向诱变和晶体学抑制剂结合研究证实溶菌酶样结构域包含SLT的活性位点。
THE integrity of the bacterial cell wall depends on the balanced action of several peptidoglycan (murein) synthesizing and degrading enzymes1,2. Penicillin inhibits the enzymes responsible for peptide crosslinks in the peptidoglycan polymer3. Enzymes that act solely on the glycosidic bonds are insensitive to this antibiotic, thus offering a target for the design of antibiotics distinct from the beta-lactams. Here we report the X-ray structure of the periplasmic soluble lytic transglycosylase (SLT; M(r) 70,000) from Escherichia coli. This unique bacterial exomuramidase cleaves the beta-1,4-glycosidic bonds of peptidoglycan to produce small 1,6-anhydromuropeptides4-6. The structure of SLT reveals a 'superhelical' ring of alpha-helices with a separate domain on top which resembles the fold of lysozyme. Site-directed mutagenesis and a crystallographic inhibitor-binding study confirmed that the lysozyme-like domain contains the active site of SLT.