Interactions of designer antibiotics and the bacterial ribosomal aminoacyl-tRNA site

JB Murray, SO Meroueh, Rupert James Martin Russell, G Lentzen, J Haddad, S Mobashery

Research output: Contribution to journalArticlepeer-review

39 Citations (Scopus)

Abstract

The X-ray crystal structures for the complexes of three designer antibiotics, compounds 1, 2, and 3, bound to two models for the ribosomal aminoacyl-tRNA site (A site) at 2.5-3.0 angstrom resolution and that of neamine at 2.8 angstrom resolution are described. Furthermore, the complex of antibiotic 1 bound to the A site in the entire 30S ribosomal subunit of Thermus thermophilus is reported at 3.8 angstrom resolution. Molecular dynamics simulations revealed that the designer compounds provide additional stability to bases A1492 and A1493 in their extrahelical forms. Snapshots from the simulations were used for free energy calculations, which revealed that van der Waals and hydrophobic effects were the driving forces behind the binding of designer antibiotic 3 when compared to the parental neamine.

Original languageEnglish
Pages (from-to)129-138
Number of pages10
JournalChemistry and Biology
Volume13
DOIs
Publication statusPublished - Feb 2006

Keywords

  • CONTINUUM SOLVENT
  • CRYSTAL-STRUCTURE
  • SUBUNIT
  • RECOGNITION
  • BINDING
  • CRYSTALLOGRAPHY
  • TRANSLATION
  • SYSTEMS
  • MODEL
  • DNA

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