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Vitamin B6 derivative, pyridoxal 5-phosphate (PLP), is the cofactor to many different chemical reactions. PLP-dependent enzymes catalyze a broad range of chemistry including transamination, racemization, phosphorylation, α-decarboxylation, aldol cleavage, β and γ-elimination and replacement reactions. PLP-dependent enzymes have important roles in the metabolism of amino acids and glycogen and are found in numerous pathways, including the interconversion of α-amino acids and the biosynthesis of antibiotic compounds (Schneider et al., 2000). As ubiquitous proteins with significant metabolic functions, PLP-dependent enzymes are attractive targets for specific inhibitor design. As a cofactor, PLP forms a covalent intermediate with the substrate, generating an external aldimine. The external aldimine stabilizes the transition state carbanion formed by the deprotonation of the Cα. While considered a rather …