title: Specific beta-lactam antibiotics inhibit secretion of lipo-beta-lactamase in yeast.
abstract: The beta-lactam antibiotic cloxacillin can inhibit secretion of prokaryotic lipo-beta-lactamase into the periplasm of yeast. The results indicate that this phenomenon is specific with respect to both the antibiotic and the lipo-beta-lactamase whose secretion is affected, strongly suggesting that this involves an interaction between the enzyme and its substrates. The effect of the antibiotic on secretion is reversible. With different beta-lactam antibiotics, the clearest difference is observed between type A and type S penicillins; the former exert a strong inhibition of secretion whereas the latter exhibit a weak effect or no effect at all. Type A penicillins have been previously shown to cause a conformational change in various beta-lactamases. Mature lipo-beta-lactamase species in yeast were localized either to the periplasmic space or bound to the outer surface of the cytoplasmic membrane and thus exposed to periplasm. The results are consistent with the hypothesis that binding of cloxacillin to lipo-beta-lactamase induces a conformation on the protein that is unfavourable for its release from the membrane.
authors.affiliation: Department of Molecular Biology, Hebrew University-Hadassah Medical School, Jerusalem, Israel.
authors.forename: A
authors.initials: A
authors.lastname: London
authors.forename: O
authors.initials: O
authors.lastname: Pines
mesh_terms: D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D003023:Cloxacillin / Q000494:pharmacology; D019286:Endopeptidase K; D008074:Lipoproteins / Q000378:metabolism*; D008969:Molecular Sequence Data; D011487:Protein Conformation; D021382:Protein Sorting Signals; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000201:enzymology*; D012697:Serine Endopeptidases / Q000378:metabolism; D001618:beta-Lactamases / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D008074:Lipoproteins; D021382:Protein Sorting Signals; D012697:Serine Endopeptidases; D019286:Endopeptidase K; D001618:beta-Lactamases; D003023:Cloxacillin