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Inhibitors of Initiation Phase of Bacterial Protein Synthesis

  1. Viter Marquez,
  2. Daniel Sohmen,
  3. Daniel N Wilson

Published Online: 15 DEC 2009

DOI: 10.1002/9780470015902.a0021835

eLS

eLS

How to Cite

Marquez, V., Sohmen, D. and Wilson, D. N. 2009. Inhibitors of Initiation Phase of Bacterial Protein Synthesis. eLS. .

Author Information

  1. Gene Center and Department of Chemistry and Biochemistry, University of Munich, Munich, Germany

Publication History

  1. Published Online: 15 DEC 2009

Abstract

The initiation phase is the rate-limiting step in protein synthesis where messenger ribonucleic acid (mRNA), initiator-transfer RNA (tRNA) and ribosomal subunits are assembled together in the presence of specific initiation factors. This process is the target for a diverse subset of antibiotics that inhibit the initiation step in a variety of different ways. Dissecting the mechanism of action of these antibiotics has provided insight not only into their inhibitory action but also into the process of translation initiation itself. With the dramatic increase in resistance of bacterial strains to many clinically relevant antibiotics, the discovery of improved inhibitors is becoming more important. Because the known initiation inhibitors bind to distinct regions of the ribosome compared with clinically used antibiotics, revisiting the initiation inhibitors may open new avenues to the development of novel antimicrobial agents.

Key Concepts:

  • Initiation of protein synthesis in bacteria operates through a 30S pre-initiation complex.

  • Aurintricarboxylic acid is a nonspecific compound that in vitro at least can prevent translation initiation by perturbing binding of mRNA to the small ribosomal subunit.

  • Kasugamycin binds within the path of the mRNA on the small subunit to prevent correct interaction between initiator tRNA and start codon to prevent translation initiation.

  • Binding of edeine to the small subunit induces base pair formation between G795 and C693 and prevents binding of initiator tRNA to the small subunit.

  • Pactamycin binds in the E-site in the path of the mRNA and prevents the first translocation reaction in a tRNA-dependent fashion.

  • Evernimicin binds to the large subunit and prevents IF2-dependent formation of the 70S initiation complex.

  • The tetrapeptide GE81112 binds to the 30S subunit to inhibit 30S initiation complex formation.

  • Antibiotics that inhibit translation also induce ribosomal assembly defects.

Keywords:

  • antibiotics;
  • initiation;
  • ribosomes;
  • RNA;
  • antibiotic resistance