D-alanine-D-alanine ligase (Ddl) (Ddl)

D-alanine-D-alanine ligase (Ddl) is an essential bacterial enzyme that catalyzes the ATP-dependent formation of the D-alanyl-D-alanine dipeptide [UniProt]. This dipeptide is a crucial precursor for the synthesis of peptidoglycan, the primary structural component of the bacterial cell wall [Wikipedia]. Since the D-alanine pathway is absent in humans, Ddl is a highly selective target for the development of antibacterial agents [PubChem]. The antibiotic D-cycloserine acts as a structural analog of D-alanine and competitively inhibits Ddl, thereby disrupting cell wall assembly and leading to bacterial lysis [StatPearls]. Ddl is particularly significant in the treatment of Mycobacterium tuberculosis, where it serves as a target for second-line therapeutic interventions [PubMed]. Inhibition of this enzyme effectively halts the late stages of cell wall precursor synthesis, making it a validated target for overcoming certain types of antibiotic resistance [Journal of Biological Chemistry].

Other names

D-alanyl-D-alanine synthetase [Wikipedia]D-alanine:D-alanine ligase (ADP-forming) [UniProt]DdlA [UniProt]DdlB [UniProt]

Competitive inhibition of the enzyme's active site, preventing the ligation of two D-alanine molecules into the D-alanyl-D-alanine dipeptide required for peptidoglycan synthesis [StatPearls].