Alanine racemase (Alr) is a pyridoxal-5'-phosphate-dependent (PLP) enzyme that catalyzes a reversible racemization between the enantiomers of alanine. d-Alanine is an indispensable constituent in the biosynthesis of bacterial cell-wall peptidoglycan, and its inhibition is lethal to prokaryotes, which makes it an attractive target for designing antibacterial drugs. In this study, the molecular structure of alanine racemase from Bacillus pseudofirmus OF4 (DadX) was determined by X-ray crystallography to a resolution of 1.8 Å. The comparison of DadX with alanine racemases from other bacteria demonstrated a conserved overall fold. Enzyme kinetics analysis showed that the conserved residues at the substrate entryway and the salt bridge at the dimer interface are critical for enzyme activity. These structural and biochemical findings provide a template for future structure-based drug-development efforts targeting alanine racemases.
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