title: The mechanism of microcin C resistance provided by the MccF peptidase.
abstract: The heptapeptide-nucleotide microcin C (McC) is a potent inhibitor of enteric bacteria growth. Inside a sensitive cell, McC is processed by aminopeptidases, which release a nonhydrolyzable aspartyl-adenylate, a strong inhibitor of aspartyl-tRNA synthetase. The mccABCDE operon is sufficient for McC production and resistance of the producing cell to McC. An additional gene, mccF, which is adjacent to but not part of the mccABCDE operon, also provides resistance to exogenous McC. MccF is similar to Escherichia coli LdcA, an L,D-carboxypeptidase whose substrate is monomeric murotetrapeptide L-Ala-D-Glu-meso-A(2)pm-D-Ala or its UDP-activated murein precursor. The mechanism by which MccF provides McC resistance remained unknown. Here, we show that MccF detoxifies both intact and processed McC by cleaving an amide bond between the C-terminal aspartate and the nucleotide moiety. MccF also cleaves the same bond in nonhydrolyzable aminoacyl sulfamoyl adenosines containing aspartyl, glutamyl, and, to a lesser extent, seryl aminoacyl moieties but is ineffective against other aminoacyl adenylates.
authors.affiliation: Institutes of Molecular Genetics and Gene Biology, Russian Academy of Sciences, Moscow, Russia.
authors.forename: Anton
authors.initials: A
authors.lastname: Tikhonov
authors.forename: Teymur
authors.initials: T
authors.lastname: Kazakov
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Semenova
authors.forename: Marina
authors.initials: M
authors.lastname: Serebryakova
authors.forename: Gaston
authors.initials: G
authors.lastname: Vondenhoff
authors.forename: Arthur
authors.initials: A
authors.lastname: Van Aerschot
authors.forename: John S
authors.initials: JS
authors.lastname: Reader
authors.forename: Vadim M
authors.initials: VM
authors.lastname: Govorun
authors.forename: Konstantin
authors.initials: K
authors.lastname: Severinov
mesh_terms: D001226:Aspartate-tRNA Ligase / Q000037:antagonists & inhibitors; D001430:Bacteriocins / Q000378:metabolism / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial / Q000187:drug effects / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000378:metabolism / Q000494:pharmacology*; D004926:Escherichia coli / Q000201:enzymology* / Q000235:genetics; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism*; D009876:Operon / Q000502:physiology; D010447:Peptide Hydrolases / Q000235:genetics / Q000378:metabolism*; D010457:Peptidoglycan / Q000235:genetics / Q000378:metabolism
chemical_list: D001430:Bacteriocins; D004791:Enzyme Inhibitors; D029968:Escherichia coli Proteins; D010457:Peptidoglycan; C020411:microcin; D010447:Peptide Hydrolases; D001226:Aspartate-tRNA Ligase