Crystal structure of Escherichia coli UDPMurNAc-tripeptide D-alanyl-D-alanine-adding enzyme (MurF) at 2.3 Å resolution

MurF is required to catalyze the final step in the synthesis of the cytoplasmic precursor of the bacterial cell wall peptidoglycan, rendering it an attractive target for antibacterial drug development. The crystal structure of the MurF ape-enzyme hiss been determined using the multiwavelength anomalous dispersion method and refined to 2.3 Angstrom resolution. It contains three consecutive open alpha/beta -sheet domains. In comparison with the complex crystal structures of MurD and its substrates, The topology of the N-terminal domain of MurF is unique, while its central and C-terminal domains exhibit similar mononucleotide and dinucleotide-binding folds, respectively. The ape-enzyme of MurF crystal structure reveals an open conformation with the three domains juxtaposed in a crescent-like arrangement creating a wide-open space where substrates are expected to bind. As such, catalysis is not feasible and significant domain closure is expected upon substrate binding. (C) 2000 Academic Press.