Confirmation of the antibacterial mode of action of SB-219383, a novel tyrosyl tRNA synthetase inhibitor from a Micromonospora sp.
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.
Greenwood
Rebecca C
RC
Department of Microbiology, GlaxoSmithKline, Collegeville, PA 19426, USA.
Gentry
Daniel R
DR
D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology*; D003470:Culture Media; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005663:Furans / Q000494:pharmacology*; D006159:Guanosine Tetraphosphate / Q000378:metabolism; D007930:Leucine / Q000378:metabolism; D008847:Micromonospora / Q000378:metabolism*; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000201:enzymology / Q000254:growth & development; D013296:Streptococcus pneumoniae / Q000187:drug effects* / Q000201:enzymology / Q000254:growth & development; D014448:Tyrosine-tRNA Ligase / Q000037:antagonists & inhibitors*; D014529:Uridine / Q000378:metabolism
D019086:Bridged Bicyclo Compounds, Heterocyclic; D003470:Culture Media; D004791:Enzyme Inhibitors; D005663:Furans; C410784:SB 219383; D006159:Guanosine Tetraphosphate; D014448:Tyrosine-tRNA Ligase; D007930:Leucine; D014529:Uridine