The mechanism of microcin C resistance provided by the MccF peptidase.
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.
Tikhonov
Anton
A
Institutes of Molecular Genetics and Gene Biology, Russian Academy of Sciences, Moscow, Russia.
Kazakov
Teymur
T
Semenova
Ekaterina
E
Serebryakova
Marina
M
Vondenhoff
Gaston
G
Van Aerschot
Arthur
A
Reader
John S
JS
Govorun
Vadim M
VM
Severinov
Konstantin
K
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
D001430:Bacteriocins; D004791:Enzyme Inhibitors; D029968:Escherichia coli Proteins; D010457:Peptidoglycan; C020411:microcin; D010447:Peptide Hydrolases; D001226:Aspartate-tRNA Ligase