UDP-N-acetylmuramoyl-L-alanyl-D-glutamate--L-lysine ligase (MurE) (MurE)

Bacterial MurE, also known as UDP-N-acetylmuramoyl-L-alanyl-D-glutamate--L-lysine ligase or meso-diaminopimelate ligase, is an essential enzyme in the cytoplasmic phase of peptidoglycan biosynthesis [1, 4]. It catalyzes the ATP-dependent addition of the third amino acid—typically L-lysine in Gram-positive bacteria or meso-diaminopimelate in Gram-negative bacteria—to the UDP-N-acetylmuramoyl-L-alanyl-D-glutamate precursor [2, 14]. This step is vital for the formation of the peptidoglycan stem peptide, which provides the structural integrity and osmotic stability necessary for bacterial survival [12, 16]. Because MurE is unique to bacteria and lacks a human homolog, it represents a highly attractive target for the development of novel, narrow- or broad-spectrum antibiotics [6, 15]. Experimental inhibitors, including phosphinate analogs, sulfonamides, and rhodanine derivatives, have demonstrated the potential to disrupt cell wall assembly, leading to bacterial lysis and death [3, 9, 13]. Although no MurE-targeted drugs are currently in clinical use, the enzyme remains a key focus for research aimed at overcoming multidrug-resistant bacterial infections [11, 15].

Other names

MurE synthetaseUDP-N-acetylmuramoyl-L-alanyl-D-glutamate--2,6-diaminopimelate ligaseL-lysine-adding enzymeUDP-MurNAc-tripeptide synthetaseUDP-N-acetylmuramyl-tripeptide synthetasemeso-diaminopimelate-adding enzymeUDP-MurNAc-L-Ala-D-Glu:L-Lys ligase

Inhibition of the ATP-dependent ligation of the third amino acid (L-lysine or meso-diaminopimelate) to the peptidoglycan precursor, leading to defective cell wall synthesis and bacterial lysis [3, 6, 13].