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

• Published in: Nature (London) 1994-02, Vol.367 (6465), p.750-753
• Main Authors: Thunnissen, Andy-Mark W. H, Dijkstra, Arnoud J, Kalk, Kor H, Rozeboom, Henriëtte J, Engel, Henk, Keck, Wolfgang, Dijkstra, Bauke W
• Format: Article
• Language: English
• Subjects: Bacteria; Bacteriology; Binding Sites; Biological and medical sciences; Crystallography; Crystallography, X-Ray; E coli; Egg White; Escherichia coli - enzymology; Fundamental and applied biological sciences. Psychology; Glycosyltransferases; Humanities and Social Sciences; Insects; letter; Microbiology; Models, Molecular; Morphology, structure, chemical composition; multidisciplinary; Muramidase - chemistry; Mutagenesis, Site-Directed; Science; Science (multidisciplinary); Transferases - chemistry
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/367750a0

THE integrity of the bacterial cell wall depends on the balanced action of several peptidoglycan (murein) synthesizing and degrading enzymes 1,2 . Penicillin inhibits the enzymes responsible for pep-tide crosslinks in the peptidoglycan polymer 3 . 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 β-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 β-l,4-glycosidic bonds of peptidoglycan to produce small 1,6-anhydro-muropeptides 4–6 . The structure of SLT reveals a 'superhelicaP ring of α-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.