Chemically related 4,5-linked aminoglycoside antibiotics drive subunit rotation in opposite directions. Academic Article uri icon

Overview

MeSH

  • Binding Sites
  • Escherichia coli
  • Escherichia coli Proteins
  • Framycetin
  • Neomycin
  • Paromomycin
  • Ribosomes
  • Ribostamycin
  • Rotation

MeSH Major

  • Aminoglycosides
  • Anti-Bacterial Agents
  • RNA, Bacterial
  • Ribosome Subunits, Large, Bacterial
  • Ribosome Subunits, Small, Bacterial

abstract

  • Dynamic remodelling of intersubunit bridge B2, a conserved RNA domain of the bacterial ribosome connecting helices 44 (h44) and 69 (H69) of the small and large subunit, respectively, impacts translation by controlling intersubunit rotation. Here we show that aminoglycosides chemically related to neomycin-paromomycin, ribostamycin and neamine-each bind to sites within h44 and H69 to perturb bridge B2 and affect subunit rotation. Neomycin and paromomycin, which only differ by their ring-I 6'-polar group, drive subunit rotation in opposite directions. This suggests that their distinct actions hinge on the 6'-substituent and the drug's net positive charge. By solving the crystal structure of the paromomycin-ribosome complex, we observe specific contacts between the apical tip of H69 and the 6'-hydroxyl on paromomycin from within the drug's canonical h44-binding site. These results indicate that aminoglycoside actions must be framed in the context of bridge B2 and their regulation of subunit rotation.

publication date

  • July 30, 2015

has subject area

  • Aminoglycosides
  • Anti-Bacterial Agents
  • Binding Sites
  • Escherichia coli
  • Escherichia coli Proteins
  • Framycetin
  • Neomycin
  • Paromomycin
  • RNA, Bacterial
  • Ribosome Subunits, Large, Bacterial
  • Ribosome Subunits, Small, Bacterial
  • Ribosomes
  • Ribostamycin
  • Rotation

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC4522699

Digital Object Identifier (DOI)

  • 10.1038/ncomms8896

PubMed ID

  • 26224058

Additional Document Info

start page

  • 7896

volume

  • 6