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

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Abstract
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 pep-tide 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 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-muropeptides4–6. 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.