A steric block in translation caused by the antibiotic spectinomycin

ACS Chem Biol. 2007 Aug 17;2(8):545-552. doi: 10.1021/cb700100n. Epub 2007 Aug 10.

Abstract

The widely used antibiotic spectinomycin inhibits bacterial protein synthesis by blocking translocation of messenger RNA and transfer RNAs on the ribosome. Here, we show that in crystals of the Escherichia coli 70S ribosome spectinomycin binding traps a distinct swiveling state of the head domain of the small ribosomal subunit. Spectinomycin also alters the rate and completeness of reverse translocation in vitro. These structural and biochemical data indicate that in solution spectinomycin sterically blocks swiveling of the head domain of the small ribosomal subunit and thereby disrupts the translocation cycle.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / metabolism
  • Anti-Bacterial Agents / pharmacology*
  • Escherichia coli
  • Molecular Conformation
  • Protein Biosynthesis / drug effects*
  • Protein Biosynthesis / physiology
  • Protein Structure, Secondary / drug effects
  • Protein Structure, Secondary / physiology
  • RNA, Bacterial / chemistry
  • RNA, Bacterial / metabolism
  • RNA, Ribosomal / chemistry
  • RNA, Ribosomal / metabolism
  • Ribosomal Proteins / chemistry
  • Ribosomal Proteins / metabolism
  • Spectinomycin / chemistry
  • Spectinomycin / metabolism
  • Spectinomycin / pharmacology*

Substances

  • Anti-Bacterial Agents
  • RNA, Bacterial
  • RNA, Ribosomal
  • Ribosomal Proteins
  • Spectinomycin

Associated data

  • PDB/2QOU
  • PDB/2QOV
  • PDB/2QOW
  • PDB/2QOX
  • PDB/2QOY
  • PDB/2QOZ
  • PDB/2QP0
  • PDB/2QP1