title: Mechanism of action of the uridyl peptide antibiotics: an unexpected link to a protein-protein interaction site in translocase MraY.
abstract: The pacidamycin and muraymycin uridyl peptide antibiotics show some structural resemblance to an Arg-Trp-x-x-Trp sequence motif for protein-protein interaction between bacteriophage ϕX174 protein E and E. coli translocase MraY. Members of the UPA class, and a synthetic uridine-peptide analogue, were found to show reduced levels of inhibition to F288L or E287A mutant MraY enzymes, implying that the UPAs interact at this extracellular site as part of the enzyme inhibition mechanism.
authors.affiliation: Department of Chemistry, University of Warwick, Coventry CV4 7AL, UK. T.D.Bugg@warwick.ac.uk.
authors.forename: Maria T
authors.initials: MT
authors.lastname: Rodolis
authors.forename: Agnes
authors.initials: A
authors.lastname: Mihalyi
authors.forename: Christian
authors.initials: C
authors.lastname: Ducho
authors.forename: Kornelia
authors.initials: K
authors.lastname: Eitel
authors.forename: Bertolt
authors.initials: B
authors.lastname: Gust
authors.forename: Rebecca J M
authors.initials: RJ
authors.lastname: Goss
authors.forename: Timothy D H
authors.initials: TD
authors.lastname: Bugg
mesh_terms: D020816:Amino Acid Motifs; D019943:Amino Acid Substitution; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D001435:Bacteriophages / Q000378:metabolism; D004926:Escherichia coli / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000378:metabolism; D009711:Nucleotides / Q000737:chemistry / Q000378:metabolism; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D011741:Pyrimidine Nucleosides / Q000737:chemistry / Q000378:metabolism; D014166:Transferases / Q000737:chemistry / Q000378:metabolism; D014508:Urea / Q000737:chemistry / Q000378:metabolism; D014529:Uridine / Q000737:chemistry*; D014764:Viral Proteins / Q000737:chemistry / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; C029555:E protein, bacteriophage X174; D029968:Escherichia coli Proteins; D009711:Nucleotides; D010455:Peptides; D011741:Pyrimidine Nucleosides; D014764:Viral Proteins; C475706:muraymycin A1; C569211:pacidamycin D; C059936:pacidamycin 1; D014508:Urea; D014166:Transferases; D014529:Uridine