Type III Pyridoxal 5-phosphate (PLP)-Dependent Enzyme Alanine Racemase
This family includes predominantly bacterial alanine racemases (AR), some serine racemases (SerRac), and putative bifunctional enzymes containing N-terminal UDP-N-acetylmuramoyl-tripeptide:D-alanyl-D-alanine ligase (murF) and C-terminal AR domains. These proteins are fold type III PLP-dependent enzymes that play essential roles in peptidoglycan biosynthesis. AR catalyzes the interconversion between L- and D-alanine, which is an essential component of the peptidoglycan layer of bacterial cell walls. SerRac converts L-serine into its D-enantiomer (D-serine) for peptidoglycan synthesis. murF catalyzes the addition of D-Ala-D-Ala to UDPMurNAc-tripeptide, the final step in the synthesis of the cytoplasmic precursor of bacterial cell wall peptidoglycan. Members of this family contain an N-terminal PLP-binding TIM-barrel domain and a C-terminal beta-sandwich domain. They exist as homodimers with active sites that lie at the interface between the TIM barrel domain of one subunit and the beta-sandwich domain of the other subunit. AR and other members of this family require dimer formation and the presence of the PLP cofactor for catalytic activity. Fungal ARs and eukaryotic serine racemases, which are fold types I and II PLP-dependent enzymes respectively, are excluded from this family.
Comment:The active site is composed of residues from both subunits of the dimer. There are two active sites in the functional dimer. Only one subunit of the dimer is shown in the 1RCQ structure.
Structure:1RCQ_A; Pseudomonas aeruginosa alanine racemase binds PLP and a guest substrate (D-lysine); defined at 4A contacts.
Structure:1L6G_AB; Geobacillus stearothermophilus alanine racemase dimer binds two cofactor-substrate complexes, PLP-D-alanine; defined at 4A contacts.
Jiyao W et al.(2023). "The conserved domain database in 2023.",