Summary: Cys/Met metabolism PLP-dependent enzyme
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Cys/Met metabolism PLP-dependent enzyme family Edit Wikipedia article
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cystathionine beta-lyase (cbl) from escherichia coli in complex with n-hydrazinocarbonylmethyl-2-trifluoromethyl-benzamide
In molecular biology, the Cys/Met metabolism PLP-dependent enzyme family is a family of proteins including enzymes involved in cysteine and methionine metabolism which use PLP (pyridoxal-5'-phosphate) as a cofactor.
PLP is the active form of vitamin B6 (pyridoxine or pyridoxal). PLP is a versatile catalyst, acting as a coenzyme in a multitude of reactions, including decarboxylation, deamination and transamination. 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 . Inadequate levels of pyridoxal phosphate in the brain can cause neurological dysfunction, particularly epilepsy.
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.
A number of pyridoxal-dependent enzymes involved in the metabolism of cysteine, homocysteine and methionine have been shown, 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.
There are five different structurally related types of PLP enzymes. Members of this family belong to the type I and are:
- in the transsulfurylation route for methionine biosynthesis:
- Cystathionine γ-synthase (metB) which joins an activated homoserine ether (acetyl or succinyl) with cysteine to form cystathionine
- Cystathionine β-lyase (metC) which splits cystathionine into homocysteine and a deaminated alanine (pyruvate and ammonia)
- in the direct sulfurylation pathway for methionine biosynthesis:
- O-acetyl homoserine sulfhydrylase (metY) which adds a thiol group to an activated homoserine ether
- O-succinylhomoserine sulfhydrylase (metZ) which adds a thiol group to an activated homoserine ether
- in the reverse transsulfurylation pathway for cysteine biosynthesis:
- Cystathionine γ-lyase (no common gene name) which joins an activated serine ether (acetyl or succinyl) with homocysteine to form cystathionine
- Not Cystathionine β-synthase which is a PLP enzyme type II
- cysteine biosynthesis from serine:
- O-acetyl serine sulfhydrylase (cysK or cysM) which adds a thiol group to an activated serine ether
- methionine degradation:
- Methionine gamma-lyase (mdeA) which breaks down methionine at the thioether and amine bounds
Note: MetC, metB, metZ are closely related and have fuzzy boundaries so fall under the same NCBI orthologue cluster (COG0626).
- Hayashi H (September 1995). "Pyridoxal enzymes: mechanistic diversity and uniformity". J. Biochem. 118 (3): 463–73. PMID 8690703.
- John RA (April 1995). "Pyridoxal phosphate-dependent enzymes". Biochim. Biophys. Acta 1248 (2): 81–96. PMID 7748903.
- Eliot AC, Kirsch JF (2004). "Pyridoxal phosphate enzymes: mechanistic, structural, and evolutionary considerations". Annu. Rev. Biochem. 73: 383–415. doi:10.1146/annurev.biochem.73.011303.074021. PMID 15189147.
- Mozzarelli A, Bettati S (2006). "Exploring the pyridoxal 5'-phosphate-dependent enzymes". Chem Rec 6 (5): 275–87. doi:10.1002/tcr.20094. PMID 17109392.
- Clayton PT (2006). "B6-responsive disorders: a model of vitamin dependency". J. Inherit. Metab. Dis. 29 (2-3): 317–26. doi:10.1007/s10545-005-0243-2. PMID 16763894.
- Toney MD (January 2005). "Reaction specificity in pyridoxal phosphate enzymes". Arch. Biochem. Biophys. 433 (1): 279–87. doi:10.1016/j.abb.2004.09.037. PMID 15581583.
- Ono B, Tanaka K, Naito K, Heike C, Shinoda S, Yamamoto S, Ohmori S, Oshima T, Toh-e A (May 1992). "Cloning and characterization of the CYS3 (CYI1) gene of Saccharomyces cerevisiae". J. Bacteriol. 174 (10): 3339–47. PMC 206003. PMID 1577698.
- Barton AB, Kaback DB, Clark MW, Keng T, Ouellette BF, Storms RK, Zeng B, Zhong W, Fortin N, Delaney S (April 1993). "Physical localization of yeast CYS3, a gene whose product resembles the rat gamma-cystathionase and Escherichia coli cystathionine gamma-synthase enzymes". Yeast 9 (4): 363–9. doi:10.1002/yea.320090406. PMID 8511966.
- Aitken, S. M.; Lodha, P. H.; Morneau, D. J. K. (2011). "The enzymes of the transsulfuration pathways: Active-site characterizations". Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics 1814 (11): 1511. doi:10.1016/j.bbapap.2011.03.006.
Cys/Met metabolism PLP-dependent enzyme Provide feedback
This family includes enzymes involved in cysteine and methionine metabolism. The following are members: Cystathionine gamma-lyase, Cystathionine gamma-synthase, Cystathionine beta-lyase, Methionine gamma-lyase, OAH/OAS sulfhydrylase, O-succinylhomoserine sulfhydrylase All of these members participate is slightly different reactions. All these enzymes use PLP (pyridoxal-5'-phosphate) as a cofactor.
Clausen T, Huber R, Laber B, Pohlenz HD, Messerschmidt A; , J Mol Biol 1996;262:202-224.: Crystal structure of the pyridoxal-5'-phosphate dependent cystathionine beta-lyase from Escherichia coli at 1.83 A. PUBMED:8831789 EPMC:8831789
Internal database links
|Similarity to PfamA using HHSearch:||Aminotran_1_2 Aminotran_5 Beta_elim_lyase DegT_DnrJ_EryC1 GDC-P Pyridoxal_deC SelA Met_gamma_lyase|
External database links
This tab holds annotation information from the InterPro database.
InterPro entry IPR000277
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 [PUBMED:8690703, PUBMED:7748903, PUBMED: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 [PUBMED:17109392]. Inadequate levels of pyridoxal phosphate in the brain can cause neurological dysfunction, particularly epilepsy [PUBMED: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 [PUBMED:15581583].
A number of pyridoxal-dependent enzymes involved in the metabolism of cysteine, homocysteine and methionine have been shown [PUBMED:1577698, PUBMED:8511966] 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.
|Molecular function||pyridoxal phosphate binding (GO:0030170)|
|Biological process||cellular amino acid metabolic process (GO:0006520)|
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This superfamily contains a variety of PLP-dependent enzymes.
The clan contains the following 15 members:Alliinase_C Aminotran_1_2 Aminotran_3 Aminotran_5 Aminotran_MocR Beta_elim_lyase Cys_Met_Meta_PP DegT_DnrJ_EryC1 GDC-P Met_gamma_lyase OKR_DC_1 Pyridoxal_deC SelA SHMT SLA_LP_auto_ag
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1Cannot generate PP/Heatmap alignments for seeds; no PP data available
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Curation and family details
|Seed source:||Pfam-B_366 (release 3.0)|
|Author:||Finn RD, Bateman A|
|Number in seed:||30|
|Number in full:||12248|
|Average length of the domain:||368.30 aa|
|Average identity of full alignment:||34 %|
|Average coverage of the sequence by the domain:||93.53 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||15|
|Download:||download the raw HMM for this family|
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