Pyridoxal-phosphate binding site
IPR021115
Definition
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 [[cite:PMID:8690703], [cite:PMID:7748903], [cite: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 ε-amino group of an active site lysine residue on the enzyme. The α-amino group of the substrate displaces the lysine ε-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 [[cite:PMID:8181483], [cite: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; L-aspartate decarboxylase, which converts aspartate to beta-alanine PMID:24415726; and phenylacetaldehyde synthase that catalyses the decarboxylation of L-phenylalanine to 2-phenylethylamine PMID:16766535. These enzymes belong to the group II decarboxylases [[cite:PMID:8181483], [cite:PMID:8889823]]. This signature contains the pyridoxal-phosphate-binding lysine residue. Certain pyridoxal-dependent decarboxylases seem to share regions of sequence similarity [[cite:PMID:2124279], [cite:PMID:2300558], [cite:PMID:8181483], [cite: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, include: 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. Cysteine sulphinic acid decarboxylase ([ec:4.1.1.29]). L-2,4-diaminobutyrate decarboxylase ([ec:4.1.1.86]) (DABA decarboxylase). This entry also includes phenylacetaldehyde synthase and 4-hydroxyphenylacetaldehyde synthase from plants and 3,4-dihydroxyphenylacetaldehyde synthase from insects. Plant aromatic acetaldehyde syntheses (AASs) are effectively indistinguishable from plant aromatic amino acid decarboxylases (AAADs) through primary sequence comparison PMID:22266321. Proteins of the AAAD family are grouped together as a result of their high homology, pyridoxal-5'-phosphate (PLP) dependence, and aromatic substrate requirements PMID:22266321. Similarly 3,4-dihydroxylphenylacetaldehyde (DHPAA) from Aedes aegypti (Yellowfever mosquito) is classified into the aromatic amino acid decarboxylase (AAAD) family based on extremely high sequence homology (about 70%) with dopa decarboxylase (Ddc) but has been shown to catalyse the production of 3,4-dihydroxylphenylacetaldehyde (DHPAA) directly from L-dopa PMID:21283636.
5 human proteins with this domain
Each is a reviewed human protein in the Seroatlas serome and a potential autoantibody target; this domain groups them into one antibody-relevant category. Every entry links to its own record.
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