UDP-N-acetylmuramoyl-L-alanine:D-glutamate ligase (MurD)

UDP-N-acetylmuramoyl-L-alanine:D-glutamate ligase (MurD) is a cytoplasmic enzyme in bacteria that catalyzes the ATP-dependent addition of D-glutamic acid to UDP-N-acetylmuramoyl-L-alanine, forming the dipeptide UDP-N-acetylmuramoyl-L-alanine-D-glutamate—a key step in peptidoglycan precursor synthesis for bacterial cell walls. MurD is one of four Mur ligases (MurC–F) performing the sequential assembly of the peptide stem, is structurally characterized by three conserved domains (binding UDP substrate, ATP, and the incoming amino acid), and is essential for bacterial survival, making it a prime target for novel antibiotic development. Multiple X-ray crystal structures of MurD have been solved, providing detailed insights into its mechanism and aiding structure-guided design of new antibacterial agents. Caveats/Limitations: - No clinical drugs on the market specifically target MurD; all cited inhibitors are investigational or tool compounds. - No standardized biomarkers or established safety issues due to lack of approved therapies, but selectivity and potential for resistance are major research concerns. - MurD is essential in bacteria but not present in eukaryotes, minimizing direct safety risks to humans.

Other names

MurDUDP-N-acetylmuramoyl-L-alanine:D-glutamate ligaseMuramyl ligase DUDP-MurNAc-L-Ala:D-Glu ligase

Competitive inhibition of substrate binding site (most designed inhibitors) ATPase inhibition (by blocking ATP-binding domain)