SLOW BINDING-INHIBITION OF PHOSPHO-N-ACETYLMURAMYL-PENTAPEPTIDE-TRANSLOCASE (ESCHERICHIA-COLI) BY MUREIDOMYCIN-A

Enzymes of the membrane cycle of reactions in bacterial peptidoglycan biosynthesis remain as unexploited potential targets for antibacterial agents, The first of these enzymes, phospho-N-acetylmuramyl-pentapept ide-translocase (EC 2.7.8.13), has been overexpressed in Escherichia c old and solubilized from particulate fractions, The work of W. A. Wepp ner and F. C. Neuhaus ((1977) J. Biol. Chem. 252, 2296-2303) has been extended to establish a usable routine fluorescence-based continuous a ssay for solubilized preparations, This assay has been used in the cha racterization of the natural product, mureidomycin A as a potent slow binding inhibitor of the enzyme with K-i and K-i of 36 nM and 2 nM, r espectively.