Structural basis for potent inhibitory activity of the antibiotic tigecycline during protein synthesis. Academic Article uri icon

Overview

MeSH

  • Base Sequence
  • Binding Sites
  • Crystallography, X-Ray
  • Fluorescence Resonance Energy Transfer
  • Glycylglycine
  • Models, Molecular
  • Protein Biosynthesis
  • RNA, Bacterial
  • RNA, Transfer
  • Ribosomes
  • Static Electricity
  • Structure-Activity Relationship
  • Thermus thermophilus

MeSH Major

  • Anti-Bacterial Agents
  • Minocycline

abstract

  • Here we present an X-ray crystallography structure of the clinically relevant tigecycline antibiotic bound to the 70S ribosome. Our structural and biochemical analysis indicate that the enhanced potency of tigecycline results from a stacking interaction with nucleobase C1054 within the decoding site of the ribosome. Single-molecule fluorescence resonance energy transfer studies reveal that, during decoding, tigecycline inhibits the initial codon recognition step of tRNA accommodation and prevents rescue by the tetracycline-resistance protein TetM.

publication date

  • March 5, 2013

has subject area

  • Anti-Bacterial Agents
  • Base Sequence
  • Binding Sites
  • Crystallography, X-Ray
  • Fluorescence Resonance Energy Transfer
  • Glycylglycine
  • Minocycline
  • Models, Molecular
  • Protein Biosynthesis
  • RNA, Bacterial
  • RNA, Transfer
  • Ribosomes
  • Static Electricity
  • Structure-Activity Relationship
  • Thermus thermophilus

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3593886

Digital Object Identifier (DOI)

  • 10.1073/pnas.1216691110

PubMed ID

  • 23431179

Additional Document Info

start page

  • 3812

end page

  • 3816

volume

  • 110

number

  • 10