Specific, efficient, and selective inhibition of prokaryotic translation initiation by a novel peptide antibiotic.
Many known antibiotics target the translational apparatus, but none of them can selectively inhibit initiation of protein synthesis and/or is prokaryotic-specific. This article describes the properties of GE81112, an effective and prokaryotic-specific initiation inhibitor. GE81112 is a natural tetrapeptide produced by a Streptomyces sp. identified by an in vitro high-throughput screening test developed to find inhibitors of the prokaryotic translational apparatus preferentially acting on steps other than elongation. In vivo GE81112 inhibits protein synthesis but not other cell functions such as DNA duplication, transcription, and cell wall synthesis. In vitro GE81112 was found to target the 30S ribosomal subunit and to interfere with both coded and noncoded P-site binding of fMet-tRNA, thereby selectively inhibiting formation of the 30S initiation complex.
Brandi
Letizia
L
Laboratory of Genetics, Department of Biology MCA, University of Camerino, 62032 Camerino (MC), Italy.
Fabbretti
Attilio
A
La Teana
Anna
A
Abbondi
Monica
M
Losi
Daniele
D
Donadio
Stefano
S
Gualerzi
Claudio O
CO
D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D004926:Escherichia coli; D007700:Kinetics; D008156:Luciferases; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D009842:Oligopeptides / Q000737:chemistry / Q000494:pharmacology*; D010442:Peptide Chain Initiation, Translational / Q000187:drug effects* / Q000502:physiology; D039662:Prokaryotic Initiation Factors / Q000037:antagonists & inhibitors*; D012358:RNA, Transfer, Met / Q000378:metabolism*; D012270:Ribosomes / Q000378:metabolism; D012588:Scintillation Counting; D013302:Streptomyces / Q000737:chemistry*; D014316:Tritium
D000900:Anti-Bacterial Agents; D009842:Oligopeptides; D039662:Prokaryotic Initiation Factors; D012358:RNA, Transfer, Met; D014316:Tritium; D008156:Luciferases