DOUGHNUT-SHAPED STRUCTURE OF A BACTERIAL MURAMIDASE REVEALED BY X-RAYCRYSTALLOGRAPHY

THE integrity of the bacterial cell wall depends on the balanced actio n of several peptidoglycan (murein) synthesizing and degrading enzymes 1,2. Penicillin inhibits the enzymes responsible for peptide crosslink s in the peptidoglycan polymer3. Enzymes that act solely on the glycos idic 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 transglyco sylase (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 reve als a 'superhelical' ring of alpha-helices with a separate domain on t op which resembles the fold of lysozyme. Site-directed mutagenesis and a crystallographic inhibitor-binding study confirmed that the lysozym e-like domain contains the active site of SLT.