Aspartyl-tRNA synthetase is the target of peptide nucleotide antibiotic Microcin C.
Microcin C is a ribosome-synthesized heptapeptide that contains a modified adenosine monophosphate covalently attached to the C-terminal aspartate. Microcin C is a potent inhibitor of bacterial cell growth. Based on the in vivo kinetics of inhibition of macromolecular synthesis, Microcin C targets translation, through a mechanism that remained undefined. Here, we show that Microcin C is a subject of specific degradation inside the sensitive cell. The product of degradation, a modified aspartyl-adenylate containing an N-acylphosphoramidate linkage, strongly inhibits translation by blocking the function of aspartyl-tRNA synthetase.
Metlitskaya
Anastasia
A
Institute of Molecular Genetics, Russian Academy of Sciences, Moscow 123182, Russia.
Kazakov
Teymur
T
Kommer
Aigar
A
Pavlova
Olga
O
Praetorius-Ibba
Mette
M
Ibba
Michael
M
Krasheninnikov
Igor
I
Kolb
Vyacheslav
V
Khmel
Inessa
I
Severinov
Konstantin
K
D049148:Aminoacylation; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000493:pharmacokinetics*; D001226:Aspartate-tRNA Ligase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D001430:Bacteriocins / Q000737:chemistry / Q000493:pharmacokinetics*; D004926:Escherichia coli / Q000187:drug effects* / Q000235:genetics; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects*; D006868:Hydrolysis; D066298:In Vitro Techniques; D014176:Protein Biosynthesis / Q000187:drug effects*
D000900:Anti-Bacterial Agents; D001430:Bacteriocins; C020411:microcin; D001226:Aspartate-tRNA Ligase