The fungal product terreic acid is a covalent inhibitor of the bacterial cell wall biosynthetic enzyme UDP-N-acetylglucosamine 1-carboxyvinyltransferase (MurA) .

ABSTRACT: Terreic acid is a metabolite with antibiotic properties produced by the fungus Aspergillus terreus. We found that terreic acid is a covalent inhibitor of the bacterial cell wall biosynthetic enzyme MurA from Enterobacter cloacae and Escherichia coli in vitro. The crystal structure of the MurA dead-end complex with terreic acid revealed that the quinine ring is covalently attached to the thiol group of Cys115, the molecular target of the antibiotic fosfomycin. Kinetic characterization established that the inactivation requires the presence of substrate UNAG (UDP-N-acetylglucosamine), proceeding with an inactivation rate constant k(inact) of 130 M(-1) s(-1). Although the mechanisms of inactivation are similar, fosfomycin is approximately 50 times more potent than terreic acid, and the struct

SUBMITTER: Han H 

PROVIDER: S-EPMC2884014 | biostudies-literature | 2010 May

REPOSITORIES: biostudies-literature