Inhibiting dihydrodipicolinate synthase across species: towards specificity for pathogens?
Dihydrodipicolinate synthase (DHDPS) is a key enzyme in lysine biosynthesis and an important antibiotic target. The specificity of a range of heterocyclic product analogues against DHDPS from three pathogenic species, Bacillus anthracis, Mycobacterium tuberculosis and methicillin-resistant Staphylococcus aureus, and the evolutionarily related N-acetylneuraminate lyase, has been determined. The results suggest that the development of species-specific inhibitors of DHDPS as potential antibacterials is achievable.
School of Chemistry, University of Melbourne, Vic. 3010, Australia.
Voula
V
Mitsakos
Renwick C J
RC
Dobson
F Grant
FG
Pearce
Sean R
SR
Devenish
Genevieve L
GL
Evans
Benjamin R
BR
Burgess
Matthew A
MA
Perugini
Juliet A
JA
Gerrard
Craig A
CA
Hutton
D001408:Bacillus anthracis / Q000201:enzymology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006836:Hydro-Lyases / Q000037:antagonists & inhibitors*; D009169:Mycobacterium tuberculosis / Q000201:enzymology; D013045:Species Specificity; D013211:Staphylococcus aureus / Q000201:enzymology
D004791:Enzyme Inhibitors; D006836:Hydro-Lyases; C020040:4-hydroxy-tetrahydrodipicolinate synthase