X射线晶体学揭示的一种细菌溶菌酶的甜甜圈状结构。

Doughnut-shaped structure of a bacterial muramidase revealed by X-ray crystallography.

作者信息

Thunnissen A M, Dijkstra A J, Kalk K H, Rozeboom H J, Engel H, Keck W, Dijkstra B W

机构信息

BIOSON Research Institute, Department of Chemistry, University of Groningen, The Netherlands.

出版信息

Nature. 1994 Feb 24;367(6465):750-3. doi: 10.1038/367750a0.

DOI:10.1038/367750a0

PMID:8107871

Abstract

The integrity of the bacterial cell wall depends on the balanced action of several peptidoglycan (murein) synthesizing and degrading enzymes. Penicillin inhibits the enzymes responsible for peptide crosslinks in the peptidoglycan polymer. 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-anhydromuropeptides. 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.

摘要

细菌细胞壁的完整性取决于几种肽聚糖（胞壁质）合成酶和降解酶的平衡作用。青霉素抑制负责肽聚糖聚合物中肽交联的酶。仅作用于糖苷键的酶对这种抗生素不敏感，因此为设计不同于β-内酰胺类的抗生素提供了一个靶点。在此，我们报道了来自大肠杆菌的周质可溶性溶菌转糖基酶（SLT；分子量70,000）的X射线结构。这种独特的细菌外切胞壁质酶切割肽聚糖的β-1,4-糖苷键，产生小的1,6-脱水胞壁肽。SLT的结构揭示了一个α-螺旋的“超螺旋”环，顶部有一个单独的结构域，类似于溶菌酶的折叠。定点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。