title: Doughnut-shaped structure of a bacterial muramidase revealed by X-ray crystallography.
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.
authors.affiliation: BIOSON Research Institute, Department of Chemistry, University of Groningen, The Netherlands.
authors.forename: A M
authors.initials: AM
authors.lastname: Thunnissen
authors.forename: A J
authors.initials: AJ
authors.lastname: Dijkstra
authors.forename: K H
authors.initials: KH
authors.lastname: Kalk
authors.forename: H J
authors.initials: HJ
authors.lastname: Rozeboom
authors.forename: H
authors.initials: H
authors.lastname: Engel
authors.forename: W
authors.initials: W
authors.lastname: Keck
authors.forename: B W
authors.initials: BW
authors.lastname: Dijkstra
mesh_terms: D001665:Binding Sites; D018360:Crystallography, X-Ray; D004529:Egg White; D004926:Escherichia coli / Q000201:enzymology*; D016695:Glycosyltransferases; D008958:Models, Molecular; D009113:Muramidase / Q000737:chemistry; D016297:Mutagenesis, Site-Directed; D014166:Transferases / Q000737:chemistry*
chemical_list: D014166:Transferases; D016695:Glycosyltransferases; C021815:murein transglycosylase; D009113:Muramidase