Pyridoxal 5'-phosphate-dependent aminotransferases and decarboxylases (PLP-dependent enzymes)

Pyridoxal 5'-phosphate (PLP)-dependent aminotransferases and decarboxylases are a diverse class of enzymes that utilize the active form of vitamin B6 to catalyze essential reactions in amino acid metabolism (NIH). These enzymes are responsible for the synthesis of key neurotransmitters such as dopamine, serotonin, and gamma-aminobutyric acid (GABA), making them critical targets in neurological and psychiatric disorders (PubMed). For instance, DOPA decarboxylase is targeted by carbidopa in Parkinson's disease, while GABA aminotransferase is inhibited by vigabatrin to treat epilepsy (NIH). Many drugs in this class act as suicide inhibitors, forming irreversible covalent bonds with the PLP cofactor to block enzymatic activity (PubMed). However, the structural conservation of the PLP-binding site across different enzymes can lead to off-target effects and safety concerns such as vitamin B6 deficiency and peripheral neuropathy (NIH).

Other names

Vitamin B6-dependent enzymesTransaminasesAmino acid decarboxylasesPLP-dependent enzymesPLP-DEs

Suicide inhibition via covalent binding to the PLP cofactor, competitive inhibition, and transaldimination mimicry.