Distinct tRNA Accommodation Intermediates Observed on the Ribosome with the Antibiotics Hygromycin A and A201A. Academic Article uri icon

Overview

MeSH

  • Crystallography, X-Ray
  • Disk Diffusion Antimicrobial Tests
  • Drug Resistance, Bacterial
  • Escherichia coli
  • Hydrogen Bonding
  • Models, Molecular
  • Protein Conformation
  • Thermus thermophilus

MeSH Major

  • Aminoglycosides
  • Anti-Bacterial Agents
  • Cinnamates
  • Hygromycin B
  • RNA, Transfer
  • Ribosome Subunits, Large, Bacterial
  • Ribosome Subunits, Small, Bacterial

abstract

  • The increase in multi-drug-resistant bacteria is limiting the effectiveness of currently approved antibiotics, leading to a renewed interest in antibiotics with distinct chemical scaffolds. We have solved the structures of the Thermus thermophilus 70S ribosome with A-, P-, and E-site tRNAs bound and in complex with either the aminocyclitol-containing antibiotic hygromycin A (HygA) or the nucleoside antibiotic A201A. Both antibiotics bind at the peptidyl transferase center and sterically occlude the CCA-end of the A-tRNA from entering the A site of the peptidyl transferase center. Single-molecule Förster resonance energy transfer (smFRET) experiments reveal that HygA and A201A specifically interfere with full accommodation of the A-tRNA, leading to the presence of tRNA accommodation intermediates and thereby inhibiting peptide bond formation. Thus, our results provide not only insight into the mechanism of action of HygA and A201A, but also into the fundamental process of tRNA accommodation during protein synthesis. Copyright © 2015 Elsevier Inc. All rights reserved.

publication date

  • June 4, 2015

has subject area

  • Aminoglycosides
  • Anti-Bacterial Agents
  • Cinnamates
  • Crystallography, X-Ray
  • Disk Diffusion Antimicrobial Tests
  • Drug Resistance, Bacterial
  • Escherichia coli
  • Hydrogen Bonding
  • Hygromycin B
  • Models, Molecular
  • Protein Conformation
  • RNA, Transfer
  • Ribosome Subunits, Large, Bacterial
  • Ribosome Subunits, Small, Bacterial
  • Thermus thermophilus

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC4458074

Digital Object Identifier (DOI)

  • 10.1016/j.molcel.2015.04.014

PubMed ID

  • 26028538

Additional Document Info

start page

  • 832

end page

  • 844

volume

  • 58

number

  • 5