Summary: Cys/Met metabolism PLP-dependent enzyme
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Cys/Met metabolism PLP-dependent enzyme family Edit Wikipedia article
|This article is an orphan, as no other articles link to it. (August 2011)|
|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. //www.ncbi.nlm.nih.gov/pmc/articles/PMC206003/.
- 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.
This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.
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.
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
|Molecular function||pyridoxal phosphate binding (GO:0030170)|
|Biological process||cellular amino acid metabolic process (GO:0006520)|
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1Cannot generate PP/Heatmap alignments for seeds; no PP data available
Key: available, not generated, — not available.
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|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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The tree is built by looking at each sequence in the full alignment for the family. We take the name of the species given by UniProt and try to map that to the full taxonomic tree from NCBI. In some cases, the name chosen by UniProt does not map to any node in the NCBI tree, perhaps because the chosen name is listed as a synonym or a misspelling in the NCBI taxonomy.
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For all of the domain matches in a full alignment, we count the number that are found on all sequences in the alignment. This total is shown in the purple box.
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There is 1 interaction for this family. More...
We determine these interactions using iPfam, which considers the interactions between residues in three-dimensional protein structures and maps those interactions back to Pfam families. You can find more information about the iPfam algorithm in the journal article that accompanies the website.
For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the Cys_Met_Meta_PP domain has been found. There are 161 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.
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