title: Anchor structure of staphylococcal surface proteins. IV. Inhibitors of the cell wall sorting reaction.
abstract: Surface proteins of Staphylococcus aureus are covalently linked to the bacterial cell wall by a mechanism requiring a COOH-terminal sorting signal with a conserved LPXTG motif. Cleavage between the threonine and the glycine of the LPXTG motif liberates the carboxyl of threonine to form an amide bond with the amino of the pentaglycine cross-bridge in the staphylococcal peptidoglycan. We asked whether antibiotic cell wall synthesis inhibitors interfere with the anchoring of surface proteins. Penicillin G, a transpeptidation inhibitor, had no effect on surface protein anchoring, whereas vancomycin and moenomycin, inhibitors of cell wall polymerization into peptidoglycan strands, slowed the sorting reaction. Cleavage of surface protein precursors did not require a mature assembled cell wall and was observed in staphylococcal protoplasts. A search for chemical inhibitors of the sorting reaction identified methanethiosulfonates and p-hydroxymercuribenzoic acid. Thus, sortase, the enzyme proposed to cleave surface proteins at the LPXTG motif, appears to be a sulfhydryl-containing enzyme that utilizes peptidoglycan precursors but not an assembled cell wall as a substrate for the anchoring of surface protein.
authors.affiliation: Department of Microbiology and Immunology, UCLA School of Medicine, Los Angeles, California 90095, USA.
authors.forename: H
authors.initials: H
authors.lastname: Ton-That
authors.forename: O
authors.initials: O
authors.lastname: Schneewind
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001426:Bacterial Proteins / Q000737:chemistry*; D002473:Cell Wall / Q000737:chemistry / Q000187:drug effects; D008565:Membrane Proteins / Q000737:chemistry; D010457:Peptidoglycan / Q000378:metabolism; D013211:Staphylococcus aureus / Q000737:chemistry* / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D008565:Membrane Proteins; D010457:Peptidoglycan