Escherichia coli peptidase A, B, or N can process translation inhibitor microcin C.
The heptapeptide-nucleotide microcin C (McC) targets aspartyl-tRNA synthetase. Upon its entry into a susceptible cell, McC is processed to release a nonhydrolyzable aspartyl-adenylate that inhibits aspartyl-tRNA synthetase, leading to the cessation of translation and cell growth. Here, we surveyed Escherichia coli cells with singly, doubly, and triply disrupted broad-specificity peptidase genes to show that any of three nonspecific oligopeptidases (PepA, PepB, or PepN) can effectively process McC. We also show that the rate-limiting step of McC processing in vitro is deformylation of the first methionine residue of McC.
Kazakov
Teymur
T
Institute of Molecular Genetics, Russian Academy of Sciences, Moscow 123182, Russia.
Vondenhoff
Gaston H
GH
Datsenko
Kirill A
KA
Novikova
Maria
M
Metlitskaya
Anastasia
A
Wanner
Barry L
BL
Severinov
Konstantin
K
D000249:Adenosine Monophosphate / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D000626:Aminopeptidases / Q000235:genetics / Q000378:metabolism; D001226:Aspartate-tRNA Ligase / Q000037:antagonists & inhibitors / Q000378:metabolism; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D001430:Bacteriocins / Q000737:chemistry / Q000378:metabolism*; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism*; D013058:Mass Spectrometry; D008666:Metalloendopeptidases / Q000235:genetics / Q000378:metabolism; D015394:Molecular Structure; D009154:Mutation; D010447:Peptide Hydrolases / Q000235:genetics / Q000378:metabolism*; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism
D001426:Bacterial Proteins; D001430:Bacteriocins; D029968:Escherichia coli Proteins; C075633:pepN protein, Bacteria; C052755:aspartyl adenylate; D001224:Aspartic Acid; D000249:Adenosine Monophosphate; D010447:Peptide Hydrolases; C028759:oligopeptidase; D000626:Aminopeptidases; D012697:Serine Endopeptidases; C090703:oligopeptidase B; D008666:Metalloendopeptidases; C057543:oligopeptidase A; D001226:Aspartate-tRNA Ligase