Pathways & interactions
Pyridoxal-phosphate binding site (IPR021115)
Short name: Pyridoxal-P_BS
Pyridoxal phosphate is the active form of vitamin B6 (pyridoxine or pyridoxal). Pyridoxal 5'-phosphate (PLP) is a versatile catalyst, acting as a coenzyme in a multitude of reactions, including decarboxylation, deamination and transamination [PMID: 8690703, PMID: 7748903, PMID: 15189147]. 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 [PMID: 17109392]. Inadequate levels of pyridoxal phosphate in the brain can cause neurological dysfunction, particularly epilepsy [PMID: 16763894].
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 [PMID: 15581583].
A number of pyridoxal-dependent decarboxylases share regions of sequence similarity, particularly in the vicinity of a conserved lysine residue, which provides the attachment site for the pyridoxal-phosphate (PLP) group [PMID: 8181483, PMID: 2124279]. Among these enzymes are aromatic-L-amino-acid decarboxylase (L-dopa decarboxylase or tryptophan decarboxylase), which catalyses the decarboxylation of tryptophan to tryptamine [PMID: 8889823]; tyrosine decarboxylase, which converts tyrosine into tyramine; and histidine decarboxylase, which catalyses the decarboxylation of histidine to histamine [PMID: 2300558]. These enzymes belong to the group II decarboxylases [PMID: 8181483, PMID: 8889823].
This signature contains the pyridoxal-phosphate-binding lysine residue. Certain pyridoxal-dependent decarboxylases seem to share regions of sequence similarity [PMID: 2124279, PMID: 2300558, PMID: 8181483, PMID: 8889823], especially in the vicinity of the lysine residue which serves as the attachment site for the pyridoxal-phosphate (PLP) group. These enzymes, known collectively as group II decarboxylases, are:
- Glutamate decarboxylase (EC:184.108.40.206) (GAD), which catalyses the decarboxylation of glutamate into the neurotransmitter GABA (4-aminobutanoate).
- Histidine decarboxylase (EC:220.127.116.11) (HDC), which catalyses the decarboxylation of histidine to histamine. There are two completely unrelated types of HDC: those that use PLP as a cofactor (found in Gram-negative bacteria and mammals), and those that contain a covalently bound pyruvoyl residue (found in Gram-positive bacteria).
- Aromatic-L-amino-acid decarboxylase (EC:18.104.22.168)(DDC; also known as L-dopa decarboxylase or tryptophan decarboxylase), which catalyses the decarboxylation of tryptophan to tryptamine. It also acts on 5-hydroxy-tryptophan and dihydroxyphenylalanine (L-dopa).
- Tyrosine decarboxylase (EC:22.214.171.124) (TyrDC), which converts tyrosine into tyramine, a precursor of isoquinoline alkaloids and various amides.
- Cysteine sulphinic acid decarboxylase (EC:126.96.36.199).
- L-2,4-diaminobutyrate decarboxylase (EC:188.8.131.52) (DABA decarboxylase).
No terms assigned in this category.
GO:0016831 carboxy-lyase activity
No terms assigned in this category.
- PS00392 (DDC_GAD_HDC_YDC)