Confirmation of the antibacterial mode of action of SB-219383, a novel tyrosyl tRNA synthetase inhibitor from a Micromonospora sp

J Antibiot (Tokyo). 2002 Apr;55(4):423-6. doi: 10.7164/antibiotics.55.423.

Abstract

The compound designated SB-219383 is a potent and selective inhibitor of bacterial tyrosyl tRNA synthetases. It exhibits an IC50 of < 1 nM against Staphylococcus aureus tyrosyl tRNA synthetase and weak in vitro activity against Staphylococci and Streptococci. Here we present data consistent with SB-219383 eliciting an amino acid starvation in both S. aureus and Streptococcus pneumoniae, supporting the conclusion that the antibacterial activity of SB-219383 is due to tyrosyl tRNA synthetase inhibition.

MeSH terms

  • Bridged Bicyclo Compounds, Heterocyclic / pharmacology*
  • Culture Media
  • Enzyme Inhibitors / pharmacology*
  • Furans / pharmacology*
  • Guanosine Tetraphosphate / metabolism
  • Leucine / metabolism
  • Micromonospora / metabolism*
  • Staphylococcus aureus / drug effects*
  • Staphylococcus aureus / enzymology
  • Staphylococcus aureus / growth & development
  • Streptococcus pneumoniae / drug effects*
  • Streptococcus pneumoniae / enzymology
  • Streptococcus pneumoniae / growth & development
  • Tyrosine-tRNA Ligase / antagonists & inhibitors*
  • Uridine / metabolism

Substances

  • Bridged Bicyclo Compounds, Heterocyclic
  • Culture Media
  • Enzyme Inhibitors
  • Furans
  • SB 219383
  • Guanosine Tetraphosphate
  • Tyrosine-tRNA Ligase
  • Leucine
  • Uridine