H
IPR015421

Pyridoxal phosphate-dependent transferase, major domain

InterPro entry
Short namePyrdxlP-dep_Trfase_major
Overlapping entries
 

Description

The monomer of PLP-dependent transferases consists of two domains, a large domain and a small domain. This entry represents the large domain, which has a 3-layer α/β/α sandwich topology
[13]
. This domain 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]
.
 * CMP-5'-(3-aminopropyl)phosphonate synthase
[15]
.
 * Canavanine gamma-lyase
[14]
.


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 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
[6]
.

References

1.Pyridoxal enzymes: mechanistic diversity and uniformity. Hayashi H. J. Biochem. 118, 463-73, (1995). View articlePMID: 8690703

2.Pyridoxal phosphate-dependent enzymes. John RA. Biochim. Biophys. Acta 1248, 81-96, (1995). View articlePMID: 7748903

3.Pyridoxal phosphate enzymes: mechanistic, structural, and evolutionary considerations. Eliot AC, Kirsch JF. Annu. Rev. Biochem. 73, 383-415, (2004). View articlePMID: 15189147

4.Exploring the pyridoxal 5'-phosphate-dependent enzymes. Mozzarelli A, Bettati S. 6, 275-87, (2006). PMID: 17109392

5.B6-responsive disorders: a model of vitamin dependency. Clayton PT. J. Inherit. Metab. Dis. 29, 317-26, (2006). View articlePMID: 16763894

6.Reaction specificity in pyridoxal phosphate enzymes. Toney MD. Arch. Biochem. Biophys. 433, 279-87, (2005). View articlePMID: 15581583

7.Crystal structure of Homo sapiens kynureninase. Lima S, Khristoforov R, Momany C, Phillips RS. Biochemistry 46, 2735-44, (2007). View articlePMID: 17300176

8.Structure of Escherichia coli tryptophanase. Ku SY, Yip P, Howell PL. Acta Crystallogr. D Biol. Crystallogr. 62, 814-23, (2006). View articlePMID: 16790938

9.Structural model of human GAD65: prediction and interpretation of biochemical and immunogenic features. Capitani G, De Biase D, Gut H, Ahmed S, Grutter MG. Proteins 59, 7-14, (2005). View articlePMID: 15690345

10.Holo- and apo-cystalysin from Treponema denticola: two different conformations. Cellini B, Montioli R, Bossi A, Bertoldi M, Laurents DV, Voltattorni CB. Arch. Biochem. Biophys. 455, 31-9, (2006). View articlePMID: 17014820

11.A three-dimensional structure of Plasmodium falciparum serine hydroxymethyltransferase in complex with glycine and 5-formyl-tetrahydrofolate. Homology modeling and molecular dynamics. Franca TC, Pascutti PG, Ramalho TC, Figueroa-Villar JD. Biophys. Chem. 115, 1-10, (2005). View articlePMID: 15848278

12.Three-dimensional structure of the Gly121Tyr dimeric form of ornithine decarboxylase from Lactobacillus 30a. Vitali J, Carroll D, Chaudhry RG, Hackert ML. Acta Crystallogr. D Biol. Crystallogr. 55, 1978-85, (1999). View articlePMID: 10666573

13.Crystal structure of LL-diaminopimelate aminotransferase from Arabidopsis thaliana: a recently discovered enzyme in the biosynthesis of L-lysine by plants and Chlamydia. Watanabe N, Cherney MM, van Belkum MJ, Marcus SL, Flegel MD, Clay MD, Deyholos MK, Vederas JC, James MN. J. Mol. Biol. 371, 685-702, (2007). View articlePMID: 17583737

14.Canavanine utilization <i>via</i> homoserine and hydroxyguanidine by a PLP-dependent γ-lyase in <i>Pseudomonadaceae</i> and <i>Rhizobiales</i>. Hauth F, Buck H, Stanoppi M, Hartig JS. RSC Chem Biol 3, 1240-1250, (2022). View articlePMID: 36320885

15.Deciphering the late biosynthetic steps of antimalarial compound FR-900098. Johannes TW, DeSieno MA, Griffin BM, Thomas PM, Kelleher NL, Metcalf WW, Zhao H. Chem Biol 17, 57-64, (2010). View articlePMID: 20142041

Cross References

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