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-pentapeptide-translocase (EC 2.7.8.13), has been overexpressed in Escherichia cold and solubilized from particulate fractions, The work of W. A. Weppner and F. C. Neuhaus ((1977) J. Biol. Chem. 252, 2296-2303) has been extended to establish a usable routine fluorescence-based continuous assay for solubilized preparations, This assay has been used in the characterization 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, respectively.