Pyridoxal 5-phosphate-dependent enzymes (PLP-dependent enzymes)

Pyridoxal 5-phosphate (PLP)-dependent enzymes, also known as vitamin B6-dependent enzymes, represent a vast and functionally diverse superfamily of catalysts essential for nitrogen metabolism [1, 2]. These enzymes utilize the PLP cofactor to facilitate a variety of chemical transformations, most notably transamination, decarboxylation, and racemization of amino acids and their derivatives [3, 4]. They play critical roles in the biosynthesis and degradation of key signaling molecules like GABA, dopamine, and serotonin, as well as the production of polyamines for cell growth and the regulation of homocysteine levels [5, 6]. Consequently, specific members of this family are major therapeutic targets; for instance, GABA aminotransferase is targeted by vigabatrin to treat epilepsy, while DOPA decarboxylase is inhibited by carbidopa in the management of Parkinson's disease [1, 8]. Pharmacological intervention typically involves suicide inhibitors that covalently modify the PLP-enzyme complex, though the structural similarity among family members necessitates careful drug design to ensure selectivity and minimize systemic side effects related to vitamin B6 interference [3, 5]. The superfamily is categorized into several distinct fold types (I-V), with Fold Type I being the most prevalent and functionally diverse group [2, 9]. [1] Amadasi A, et al. (2007) Curr Med Chem; [2] Percudani R, Peracchi A. (2003) EMBO Rep; [3] Eliot AC, Kirsch JF. (2004) Annu Rev Biochem; [5] Wu F, et al. (2011) PMC; [9] Ngo et al. (2022) Frontiers.

Other names

PLP-dependent aminotransferases and related enzymesVitamin B6-dependent enzymesB6-dependent enzymesTransaminases and related enzymesPyridoxal phosphate-dependent enzymes

Suicide inhibition (irreversible covalent binding to the PLP cofactor or active site residues), competitive inhibition, and transition-state mimicry.