InterPro domain: IPR000277
General Information
- Identifier IPR000277
- Description Cys/Met metabolism, pyridoxal phosphate-dependent enzyme
- Number of genes 635
- Gene duplication stats Loading...
- Associated GO terms GO:0030170 GO:0019346
Abstract
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 [ 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 ].
A number of pyridoxal-dependent enzymes involved in the metabolism of cysteine, homocysteine and methionine have been shown [ 7 , 8 ] to be evolutionary related. These enzymes are proteins of about 400 amino-acid residues. The pyridoxal-P group is attached to a lysine residue located in the central section of these enzymes.
One of these enzymes is the sulfhydrylase FUB7 from fungi such as Gibberella and Fusarium. The gene is part of a cluster that mediates the biosynthesis of fusaric acid, a mycotoxin with low to moderate toxicity to animals and humans, but with high phytotoxic properties [ 9 ].
1. Pyridoxal enzymes: mechanistic diversity and uniformity. J. Biochem. 118, 463-73
2. Pyridoxal phosphate-dependent enzymes. Biochim. Biophys. Acta 1248, 81-96
3. Pyridoxal phosphate enzymes: mechanistic, structural, and evolutionary considerations. Annu. Rev. Biochem. 73, 383-415
4. Exploring the pyridoxal 5'-phosphate-dependent enzymes. J. Inherit. Metab. Dis. 6, 275-87
5. B6-responsive disorders: a model of vitamin dependency. Environ. Microbiol. 29, 317-26
6. Reaction specificity in pyridoxal phosphate enzymes. Arch. Biochem. Biophys. 433, 279-87
7. Cloning and characterization of the CYS3 (CYI1) gene of Saccharomyces cerevisiae. J. Bacteriol. 174, 3339-47
8. Physical localization of yeast CYS3, a gene whose product resembles the rat gamma-cystathionase and Escherichia coli cystathionine gamma-synthase enzymes. Yeast 9, 363-9
9. Two separate key enzymes and two pathway-specific transcription factors are involved in fusaric acid biosynthesis in Fusarium fujikuroi. null 18, 936-56