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Updated: Jul 20, 2025

Chromatographic Purification of Highly Active Yeast Ribosomes
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Chromatographic Purification of Highly Active Yeast Ribosomes

Published on: October 24, 2011

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Molecular basis of the pleiotropic effects by the antibiotic amikacin on the ribosome

Savannah M Seely1, Narayan P Parajuli2, Arindam De Tarafder2

  • 1Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX, 77555, USA.

Nature Communications
|August 3, 2023
PubMed

Insights

Amikacin, an aminoglycoside antibiotic, uniquely inhibits bacterial ribosome function by interfering with tRNA translocation and recycling. This detailed mechanism, revealed by crystallography and cryo-EM, aids in designing new antibiotics.

Area of Science:

  • Molecular Biology
  • Structural Biology
  • Microbiology

Background:

  • Aminoglycosides are crucial antibiotics targeting bacterial ribosomes.
  • Amikacin, a kanamycin derivative, combats multidrug-resistant Gram-negative bacteria.
  • Amikacin's unique structure, featuring a 4-amino-2-hydroxy butyrate (AHB) moiety, suggests distinct ribosome interaction mechanisms.

Purpose of the Study:

  • To elucidate the precise mechanisms of ribosome inhibition by amikacin and kanamycin.
  • To understand how amikacin's unique structural features influence its antibacterial activity.
  • To identify potential targets for developing improved amikacin derivatives.

Main Methods:

  • In vitro fast kinetics assays.
  • X-ray crystallography.
  • Cryo-electron microscopy (cryo-EM).

Main Results:

  • Amikacin exhibits a distinct ribosome inhibition profile compared to kanamycin.
  • Amikacin interferes with key ribosomal processes: tRNA translocation, peptidyl-tRNA hydrolysis, and ribosome recycling.
  • Structural analysis reveals amikacin's additional interactions within the ribosomal decoding center.

Conclusions:

  • Amikacin's enhanced ribosome inhibition stems from unique interactions mediated by its AHB moiety.
  • The identified binding site in the large ribosomal subunit provides a basis for rational drug design.
  • This research paves the way for developing novel aminoglycoside antibiotics with improved efficacy against resistant bacteria.

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