Abstract
We report the identification of the sesquiterpene lactones cnicin and cynaropicrin as potent, irreversible inhibitors of the bacterial enzyme MurA. They covalently bind to the thiol group of Cys115. Judging from the structure-activity relationships, we conclude that the unsaturated ester side chain of cynaropicrin and cnicin is of particular importance for the inhibition of MurA. These results provide evidence that MurA is a target protein of SLs with a probably high relevance for their known antibacterial effect.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Alkyl and Aryl Transferases / antagonists & inhibitors*
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / pharmacology*
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Escherichia coli / drug effects
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Escherichia coli / enzymology
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Lactones / chemistry
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Lactones / pharmacology*
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Peptidoglycan / biosynthesis*
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Pseudomonas aeruginosa / drug effects
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Pseudomonas aeruginosa / enzymology
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Sesquiterpenes / chemistry
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Sesquiterpenes / pharmacology*
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Structure-Activity Relationship
Substances
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Enzyme Inhibitors
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Lactones
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Peptidoglycan
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Sesquiterpenes
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cnicin
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Alkyl and Aryl Transferases
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UDP-N-acetylglucosamine 1-carboxyvinyltransferase
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cynaropicrin