Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 103, Issue 1, Pages 39-44Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0507740102
Keywords
30S initiation complex; fMet-tRNA binding; P-site inhibition
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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.
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