Alanine racemase and D-alanine–D-alanine ligase (Alr (for alanine racemase), Ddl (for D-alanine–D-alanine ligase))

Alanine racemase is a pyridoxal phosphate (PLP)-dependent enzyme that catalyzes the reversible racemization of L-alanine to D-alanine, a step essential for peptidoglycan biosynthesis in bacteria. D-alanine–D-alanine ligase catalyzes the ATP-dependent ligation of two D-alanine molecules to form the dipeptide D-Ala–D-Ala, which is then incorporated into the bacterial cell wall peptide chain. Both enzymes are absent in higher eukaryotes and are essential for bacterial viability, making them prime targets for antibiotic development, particularly D-cycloserine, which inhibits both. Their inhibition leads to disruption of cell wall synthesis and bacterial lysis.

Other names

L-alanine racemaseAlrEC 5.1.1.1DdlEC 6.3.2.4

Inhibition of alanine racemase blocks racemization of L-alanine to D-alanine, depleting D-alanine needed for cell wall synthesis. Inhibition of D-alanine–D-alanine ligase blocks dipeptide formation essential for peptidoglycan crosslinking. D-cycloserine acts by irreversible covalent modification (alanine racemase), and through phosphorylation-based inhibition (D-alanine–D-alanine ligase).