CRYSTAL-STRUCTURE OF UDP-N-ACETYLMURAMOYL-L-ALANINE - D-GLUTAMATE LIGASE FROM ESCHERICHIA-COLI

UDP-N-acetylmuramoyl-L-alanine:D-glutamate ligase (MurD) is a cytoplas mic enzyme involved in the biosynthesis of peptidoglycan which catalyz es the addition of D-glutamate to the nucleotide precursor UDP-N-acety lmuramoyl-L-alanine (UMA). The crystal structure of MurD in the presen ce of its substrate UMA. has been solved to 1.9 Angstrom resolution. P hase information was obtained from multiple anomalous dispersion using the K-shell edge of selenium in combination with multiple isomorphous replacement. The structure comprises three domains of topology each r eminiscent of nucleotide-binding folds: the N- and C-terminal domains are consistent with the dinucleotide-binding fold sailed the Rossmann fold, and the central domain with the mononucleotide-binding fold also observed in the GTPase family. The structure reveals the binding site of the substrate UMA, and comparison with known NTP complexes allows the identification of residues interacting with ATP. The study describ es the first structure of the UDP-N-acetylmuramoyl-peptide ligase fami ly.