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373  structures 7900  species 0  interactions 30567  sequences 158  architectures

Family: Cys_Met_Meta_PP (PF01053)

Summary: Cys/Met metabolism PLP-dependent enzyme

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This is the Wikipedia entry entitled "Cys/Met metabolism PLP-dependent enzyme family". More...

Cys/Met metabolism PLP-dependent enzyme family Edit Wikipedia article

Cys_Met_Meta_PP
PDB 2fq6 EBI.jpg
cystathionine beta-lyase (cbl) from escherichia coli in complex with n-hydrazinocarbonylmethyl-2-trifluoromethyl-benzamide
Identifiers
Symbol Cys_Met_Meta_PP
Pfam PF01053
Pfam clan CL0061
InterPro IPR000277
PROSITE PDOC00677
SCOP 1cs1
SUPERFAMILY 1cs1
CDD cd00614

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.[1]

Mechanism of action

PLP is employed as it binds to amino groups and stabilises carbanion intermediates. 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.[2]

Function

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.[3][4][5]

A number of pyridoxal-dependent enzymes involved in the metabolism of cysteine, homocysteine and methionine have been shown to be evolutionary related.[1] These enzymes are tetrameric proteins of about 400 amino-acid residues. Each monomer has an active site, which however requires the N-terminal of another monomer to be completed (salt bridges to phosphate and entrance way). The phosphopyridoxyl group is attached to a lysine residue located in the central section of these enzymes and is stabilised by π-stacking interactions with a tyrosine residue above it.[6]

Family members

There are five different structurally related types of PLP enzymes. Members of this family belong to the type I and are:[1]

  • 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).[1]

References

  1. ^ a b c d Ferla MP, Patrick WM (2014). "Bacterial methionine biosynthesis". Microbiology. 160 (Pt 8): 1571–84. doi:10.1099/mic.0.077826-0. PMID 24939187. 
  2. ^ 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. 
  3. ^ Hayashi H (September 1995). "Pyridoxal enzymes: mechanistic diversity and uniformity". J. Biochem. 118 (3): 463–73. PMID 8690703. 
  4. ^ John RA (April 1995). "Pyridoxal phosphate-dependent enzymes". Biochim. Biophys. Acta. 1248 (2): 81–96. doi:10.1016/0167-4838(95)00025-p. PMID 7748903. 
  5. ^ 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. 
  6. ^ Aitken SM, Lodha PH, Morneau DJ (2011). "The enzymes of the transsulfuration pathways: Active-site characterizations". Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics. 1814 (11): 1511–7. doi:10.1016/j.bbapap.2011.03.006. PMID 21435402. 

This article incorporates text from the public domain Pfam and InterPro IPR000277

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

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.

Literature references

  1. 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

  2. Clausen T, Huber R, Prade L, Wahl MC, Messerschmidt A; , EMBO J 1998;17:6827-6838.: Crystal structure of Escherichia coli cystathionine gamma-synthase at 1.5 A resolution. PUBMED:9843488 EPMC:9843488


Internal database links

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.

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 [ PUBMED:26662839 ].

Gene Ontology

The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

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Pfam Clan

This family is a member of clan PLP_aminotran (CL0061), which has the following description:

This superfamily contains a variety of PLP-dependent enzymes.

The clan contains the following 16 members:

Alliinase_C Aminotran_1_2 Aminotran_3 Aminotran_5 Asp_aminotransf Beta_elim_lyase ComK Cys_Met_Meta_PP DegT_DnrJ_EryC1 GDC-P Met_gamma_lyase OKR_DC_1 Pyridoxal_deC SelA SepSecS SHMT

Alignments

We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets and the UniProtKB sequence database. More...

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We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.

  Seed
(25)
Full
(30567)
Representative proteomes UniProt
(123712)
RP15
(3977)
RP35
(13934)
RP55
(29092)
RP75
(49508)
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1Cannot generate PP/Heatmap alignments for seeds; no PP data available

Key: ✓ available, x not generated, not available.

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  Seed
(25)
Full
(30567)
Representative proteomes UniProt
(123712)
RP15
(3977)
RP35
(13934)
RP55
(29092)
RP75
(49508)
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  Seed
(25)
Full
(30567)
Representative proteomes UniProt
(123712)
RP15
(3977)
RP35
(13934)
RP55
(29092)
RP75
(49508)
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You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

HMM logo

HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...

Trees

This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

Note: You can also download the data file for the tree.

Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation View help on the curation process

Seed source: Pfam-B_366 (release 3.0)
Previous IDs: none
Type: Domain
Sequence Ontology: SO:0000417
Author: Finn RD , Bateman A
Number in seed: 25
Number in full: 30567
Average length of the domain: 366.70 aa
Average identity of full alignment: 33 %
Average coverage of the sequence by the domain: 89.65 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 57096847 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 20.9 19.7
Trusted cut-off 20.9 19.7
Noise cut-off 20.8 19.6
Model length: 382
Family (HMM) version: 22
Download: download the raw HMM for this family

Species distribution

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Structures

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 373 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 sequence.

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AlphaFold Structure Predictions

The list of proteins below match this family and have AlphaFold predicted structures. Click on the protein accession to view the predicted structure.

Protein Predicted structure External Information
A0A0P0VYR6 View 3D Structure Click here
A0A0P0WT28 View 3D Structure Click here
A0A0P0WV19 View 3D Structure Click here
A0A0R0EMR0 View 3D Structure Click here
A0A0R0I5R9 View 3D Structure Click here
A0A1D6GMP0 View 3D Structure Click here
A0A1D6I2D1 View 3D Structure Click here
A0A1D6K483 View 3D Structure Click here
A0A1D6K483 View 3D Structure Click here
A0A1D6KVU6 View 3D Structure Click here
A0A1D6KVU7 View 3D Structure Click here
A0A1D6P7H0 View 3D Structure Click here
A0A1D8PD47 View 3D Structure Click here
A0A1D8PTV7 View 3D Structure Click here
A0A1X7YHF6 View 3D Structure Click here
A4HVY9 View 3D Structure Click here
A4I885 View 3D Structure Click here
A4IBL4 View 3D Structure Click here
B4FU01 View 3D Structure Click here
F1QPF7 View 3D Structure Click here
F1R5R0 View 3D Structure Click here
I1JDK2 View 3D Structure Click here
I1JN71 View 3D Structure Click here
I1L5U9 View 3D Structure Click here
I1LXI0 View 3D Structure Click here
I1N4F6 View 3D Structure Click here
K7KPM4 View 3D Structure Click here
O02215 View 3D Structure Click here
O13326 View 3D Structure Click here
O42851 View 3D Structure Click here
O45391 View 3D Structure Click here
O53390 View 3D Structure Click here
O74314 View 3D Structure Click here
O94350 View 3D Structure Click here
P00935 View 3D Structure Click here
P06106 View 3D Structure Click here
P06721 View 3D Structure Click here
P18757 View 3D Structure Click here
P31373 View 3D Structure Click here
P32929 View 3D Structure Click here
P38716 View 3D Structure Click here
P43623 View 3D Structure Click here
P47164 View 3D Structure Click here
P53101 View 3D Structure Click here
P53780 View 3D Structure Click here
P55216 View 3D Structure Click here
P55217 View 3D Structure Click here
P9WGB5 View 3D Structure Click here
P9WGB7 View 3D Structure Click here
Q04533 View 3D Structure Click here
Q12198 View 3D Structure Click here
Q2G0V3 View 3D Structure Click here
Q2G119 View 3D Structure Click here
Q2G120 View 3D Structure Click here
Q4CM88 View 3D Structure Click here
Q4DRM4 View 3D Structure Click here
Q4DUG8 View 3D Structure Click here
Q54RW8 View 3D Structure Click here
Q55DV9 View 3D Structure Click here
Q59US5 View 3D Structure Click here
Q5A362 View 3D Structure Click here
Q5ACX5 View 3D Structure Click here
Q7JXZ2 View 3D Structure Click here
Q7XCS3 View 3D Structure Click here
Q8VCN5 View 3D Structure Click here
Q94I39 View 3D Structure Click here
Q94I44 View 3D Structure Click here
Q94I45 View 3D Structure Click here
Q94I45 View 3D Structure Click here
Q9C876 View 3D Structure Click here
Q9LWJ5 View 3D Structure Click here
Q9SGU9 View 3D Structure Click here