InterPro: IPR015422 Pyridoxal phosphate-dependent transferase, major region, subdomain 2

Pyridoxal phosphate is the active form of vitamin B6 (pyridoxine or pyridoxal). PLP is a versatile catalyst, acting as a coenzyme in a multitude of reactions, including decarboxylation, deamination and transamination [1, 2, 3]. PLP-dependent enzymes are primarily involved in the biosynthesis of amino acids and amino acid-derived metabolites, but they are also found in the biosynthetic pathways of amino sugars and in the synthesis or catabolism of neurotransmitters; pyridoxal phosphate can also inhibit DNA polymerases and several steroid receptors [4]. Inadequate levels of pyridoxal phosphate in the brain can cause neurological dysfunction, particularly epilepsy [5].

PLP enzymes exist in their resting state as a Schiff base, the aldehyde group of PLP forming a linkage with the epsilon-amino group of an active site lysine residue on the enzyme. The alpha-amino group of the substrate displaces the lysine epsilon-amino group, in the process forming a new aldimine with the substrate. This aldimine is the common central intermediate for all PLP-catalysed reactions, enzymatic and non-enzymatic [6].

This entry represents subdomain 2 of the major region of PLP-dependent transferases. This domain has a complex alpha/beta structure. The major region can be found in the following PLP-dependent transferase families:

• Aspartate aminotransferase (AAT)-like enzymes, such as aromatic aminoacid aminotransferase AroAT, glutamine aminotransferase and kynureninase [7].
• Beta-eliminating lyases, such as tyrosine phenol lyase and tryptophanase [8].
• Pyridoxal-dependent decarboxylases, such as DOPA decarboxylase and glutamate decarboxylase beta (GadB) [9].
• Cystathionine synthase-like enzymes, such as cystalysin, methionine gamma-lyase (MGL), and cysteine desulphurase (IscS) [10].
• GABA-aminotransferase-like enzymes, such as ornithine aminotransferase and serine hydroxymethyltransferase [11].
• Ornithine decarboxylase major domain [12].