Pyridoxal Phosphate-Dependent Enzyme (PLP-Dependent Enzyme)

Pyridoxal phosphate-dependent enzymes are a large and diverse class of enzymes that require pyridoxal 5'-phosphate (PLP), the active form of vitamin B6, as a coenzyme. PLP is essential for the catalytic activity of these enzymes, which are found in all domains of life and participate in numerous metabolic pathways. These enzymes catalyze a wide variety of reactions, primarily involving amino acids, including transamination, decarboxylation, deamination, racemization, β-elimination and γ-elimination/replacement reactions. These reactions are central to amino acid metabolism, neurotransmitter biosynthesis, histamine production, heme synthesis, and other critical biological processes. The key feature is the formation of a Schiff base (aldimine) between the aldehyde group on PLP and an active site lysine residue on the enzyme. The PLP cofactor acts as an electron sink to stabilize carbanionic intermediates during catalysis. Most PLP-dependent enzymes share conserved structural motifs including a three-layer α/β/α sandwich topology with mixed β-sheets and covalent attachment via Schiff base linkage to a lysine residue at the active site. Deficiency or dysfunction in vitamin B6 or its dependent enzymes can lead to neurological symptoms such as seizures due to impaired neurotransmitter synthesis (e.g., GABA). Some drugs target specific PLP-dependent enzymes for therapeutic purposes.

Other names

Vitamin B6-Dependent EnzymePLP EnzymePyridoxal 5'-Phosphate Enzyme

Formation/exchange of Schiff base; stabilization via electron sink