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

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.

• Authors: Rebecca C Greenwood, Daniel R Gentry
• Journal: The Journal of antibiotics (J Antibiot (Tokyo)) Vol. 55 Issue 4 Pg. 423-6 (Apr 2002) ISSN: 0021-8820 [Print] England
• PMID: 12061551 (Publication Type: Journal Article)

Chemical References

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

Topics

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