Binding Site

Pyridoxal-phosphate binding site (IPR021115)

Short name: Pyridoxal-P_BS

Description

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; histidine decarboxylase, which catalyses the decarboxylation of histidine to histamine [PMID: 2300558]; and L-aspartate decarboxylase, which converts aspartate to beta-alanine [PMID: 24415726]. 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:4.1.1.15) (GAD), which catalyses the decarboxylation of glutamate into the neurotransmitter GABA (4-aminobutanoate).

  • Histidine decarboxylase (EC:4.1.1.22) (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:4.1.1.28)(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:4.1.1.25) (TyrDC), which converts tyrosine into tyramine, a precursor of isoquinoline alkaloids and various amides.

  • L-2,4-diaminobutyrate decarboxylase (EC:4.1.1.86) (DABA decarboxylase).

GO terms

Biological Process

No terms assigned in this category.

Molecular Function

GO:0016831 carboxy-lyase activity

Cellular Component

No terms assigned in this category.

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.
PROSITE patterns