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758  structures 4130  species 0  interactions 32925  sequences 455  architectures

Family: GST_C (PF00043)

Summary: Glutathione S-transferase, C-terminal domain

Pfam includes annotations and additional family information from a range of different sources. These sources can be accessed via the tabs below.

This is the Wikipedia entry entitled "Glutathione S-transferase". More...

Glutathione S-transferase Edit Wikipedia article

The Glutathione S-transferase (GST) family of enzymes comprises a long list of cytosolic, mitochondrial, and microsomal proteins which are capable of multiple reactions with a multitude of substrates, both endogenous and xenobiotic.


Families of GST

  • Mammalian
    • Alpha
      • A1-1
      • A2-2
      • A3-3
      • A4-4
      • hGST5.8 (putative)
    • Mu
      • M1-1
    • Pi
      • P1-1
    • Theta
    • Zeta
    • Omega


Structure of GSTs

Mammalian cytosolic GSTs are homodimeric, and the monomers are in the range of 22-29 kDa. They are active over a wide variety of substrates with considerable overlap.

GSTs and Biotransformation

Glutathione S-transferases are considered, among several others, to contribute to the phase II biotransformation of xenobiotics. Drugs, poisons, and other compounds not traditionally listed in either groups are usually somewhat modified by the phase I and/or phase II mechanisms, and finally exreted from the body. GSTs contribute to this type of metabolism by conjugating these compounds (often electrophilic and somewhat lipophilic in nature) with reduced glutathione to facilitate dissolution in the aqueous cellular and extracelluar media, and from there, out of the body.

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

This is the Wikipedia entry entitled "Glutathione S-transferase, C-terminal domain". More...

Glutathione S-transferase, C-terminal domain Edit Wikipedia article

Glutathione S-transferase, C-terminal domain
Identifiers
SymbolGST_C
PfamPF00043
InterProIPR004046
SCOP22gst / SCOPe / SUPFAM
OPM superfamily139
OPM protein1z9h

Glutathione S-transferase, C-terminal domain is a structural domain of glutathione S-transferase (GST).

GST conjugates reduced glutathione to a variety of targets including S-crystallin from squid, the eukaryotic elongation factor 1-gamma, the HSP26 family of stress-related proteins and auxin-regulated proteins in plants.

The glutathione molecule binds in a cleft between N and C-terminal domains. The catalytically important residues are proposed to reside in the N-terminal domain. In plants, GSTs are encoded by a large gene family (48 GST genes in Arabidopsis) and can be divided into the phi, tau, theta, zeta, and lambda classes.

Biological function and classification

In eukaryotes, glutathione S-transferases (GSTs) participate in the detoxification of reactive electrophilic compounds by catalysing their conjugation to glutathione. The GST domain is also found in S-crystallins from squid, and proteins with no known GST activity, such as eukaryotic elongation factors 1-gamma and the HSP26 family of stress-related proteins, which include auxin-regulated proteins in plants and stringent starvation proteins in Escherichia coli. The major lens polypeptide of cephalopods is also a GST[1][2][3][4].

Bacterial GSTs of known function often have a specific, growth-supporting role in biodegradative metabolism: epoxide ring opening and tetrachlorohydroquinone reductive dehalogenation are two examples of the reactions catalysed by these bacterial GSTs. Some regulatory proteins, like the stringent starvation proteins, also belong to the GST family[5][6]. GST seems to be absent from Archaea in which gamma-glutamylcysteine substitute to glutathione as major thiol.

Oligomerization

Glutathione S-transferases form homodimers, but in eukaryotes can also form heterodimers of the A1 and A2 or YC1 and YC2 subunits. The homodimeric enzymes display a conserved structural fold. Each monomer is composed of a distinct N-terminal sub-domain, which adopts the thioredoxin fold, and a C-terminal all-helical sub-domain. This entry is the C-terminal domain.

Human proteins containing this domain

EEF1E1; EEF1G; GDAP1; GSTA1; GSTA2; GSTA3; GSTA4; GSTA5; GSTM1; GSTM2; GSTM3; GSTM4; GSTM5; GSTO1; GSTP1; GSTT1; GSTT2; GSTZ1; MARS; PGDS; PTGDS2; PTGES2; VARS;

References

  1. ^ Armstrong RN (1997). "Structure, catalytic mechanism, and evolution of the glutathione transferases". Chem. Res. Toxicol. 10 (1): 2–18. PMID 9074797.
  2. ^ Board PG, Coggan M, Chelvanayagam G, Easteal S, Jermiin LS, Schulte GK, Danley DE, Hoth LR, Griffor MC, Kamath AV, Rosner MH, Chrunyk BA, Perregaux DE, Gabel CA, Geoghegan KF, Pandit J (2000). "Identification, characterization, and crystal structure of the Omega class glutathione transferases". J. Biol. Chem. 275 (32): 24798–24806. PMID 10783391. {{cite journal}}: line feed character in |author= at position 34 (help)CS1 maint: multiple names: authors list (link)
  3. ^ Board P, Chelvanayagam G, Dulhunty A, Gage P, Curtis S (2001). "The glutathione transferase structural family includes a nuclear chloride channel and a ryanodine receptor calcium release channel modulator". J. Biol. Chem. 276 (5): 3319–3323. PMID 11035031.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  4. ^ Eaton DL, Bammler TK (1999). "Concise review of the glutathione S-transferases and their significance to toxicology". Toxicol. Sci. 49 (2): 156–164. PMID 10416260.
  5. ^ Parker MW, Board PG, Polekhina G, Blackburn AC (2001). "Crystal structure of maleylacetoacetate isomerase/glutathione transferase zeta reveals the molecular basis for its remarkable catalytic promiscuity". Biochemistry. 40 (6): 1567–1576. PMID 11327815.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  6. ^ Vuilleumier S (1997). "Bacterial glutathione S-transferases: what are they good for?". J. Bacteriol. 179 (5): 1431–1441. PMID 9045797.

Further reading

  • [1]. Three-dimensional structure of Escherichia coli glutathione S-transferase complexed with glutathione sulfonate: catalytic roles of Cys10 and His106. Nishida M, Harada S, Noguchi S, Satow Y, Inoue H, Takahashi K; J Mol Biol 1998;281:135-147. PMID 9680481
  • [2]. Plant glutathione transferases. Dixon DP, Lapthorn A, Edwards R; Genome Biol 2002;3:REVIEWS3004. PMID 11897031

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.

Glutathione S-transferase, C-terminal domain Provide feedback

GST conjugates reduced glutathione to a variety of targets including S-crystallin from squid, the eukaryotic elongation factor 1-gamma, the HSP26 family of stress-related proteins and auxin-regulated proteins in plants. Stringent starvation proteins in E. coli are also included in the alignment but are not known to have GST activity. The glutathione molecule binds in a cleft between N and C-terminal domains. The catalytically important residues are proposed to reside in the N-terminal domain [1]. In plants, GSTs are encoded by a large gene family (48 GST genes in Arabidopsis) and can be divided into the phi, tau, theta, zeta, and lambda classes [2].

Literature references

  1. Nishida M, Harada S, Noguchi S, Satow Y, Inoue H, Takahashi K; , J Mol Biol 1998;281:135-147.: Three-dimensional structure of Escherichia coli glutathione S-transferase complexed with glutathione sulfonate: catalytic roles of Cys10 and His106. PUBMED:9680481 EPMC:9680481

  2. Dixon DP, Lapthorn A, Edwards R; , Genome Biol 2002;3:REVIEWS3004.: Plant glutathione transferases. PUBMED:11897031 EPMC:11897031


Internal database links

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR004046

In eukaryotes, glutathione S-transferases (GSTs) participate in the detoxification of reactive electrophilic compounds by catalysing their conjugation to glutathione. The GST domain is also found in S-crystallins from squid, and proteins with no known GST activity, such as eukaryotic elongation factors 1-gamma and the HSP26 family of stress-related proteins, which include auxin-regulated proteins in plants and stringent starvation proteins in Escherichia coli. The major lens polypeptide of cephalopods is also a GST [ PUBMED:9074797 , PUBMED:10783391 , PUBMED:11035031 , PUBMED:10416260 ].

Bacterial GSTs of known function often have a specific, growth-supporting role in biodegradative metabolism: epoxide ring opening and tetrachlorohydroquinone reductive dehalogenation are two examples of the reactions catalysed by these bacterial GSTs. Some regulatory proteins, like the stringent starvation proteins, also belong to the GST family [ PUBMED:11327815 , PUBMED:9045797 ]. GST seems to be absent from Archaea in which gamma-glutamylcysteine substitute to glutathione as major thiol.

Glutathione S-transferases form homodimers, but in eukaryotes can also form heterodimers of the A1 and A2 or YC1 and YC2 subunits. The homodimeric enzymes display a conserved structural fold. Each monomer is composed of a distinct N-terminal sub-domain, which adopts the thioredoxin fold, and a C-terminal all-helical sub-domain. This entry is the C-terminal domain.

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 GST_C (CL0497), which has the following description:

This clan represents the C-terminal domain of Glutathione S-transferase.

The clan contains the following 8 members:

Glutaredoxin2_C GST_C GST_C_2 GST_C_3 GST_C_4 GST_C_5 GST_C_6 Tom37_C

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
(33)
Full
(32925)
Representative proteomes UniProt
(109982)
RP15
(4405)
RP35
(14388)
RP55
(28519)
RP75
(48363)
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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
(33)
Full
(32925)
Representative proteomes UniProt
(109982)
RP15
(4405)
RP35
(14388)
RP55
(28519)
RP75
(48363)
Alignment:
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We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.

  Seed
(33)
Full
(32925)
Representative proteomes UniProt
(109982)
RP15
(4405)
RP35
(14388)
RP55
(28519)
RP75
(48363)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download  
Gzipped Download   Download   Download   Download   Download   Download   Download  

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: Overington
Previous IDs: gluts; GST;
Type: Domain
Sequence Ontology: SO:0000417
Author: Eddy SR , Griffiths-Jones SR
Number in seed: 33
Number in full: 32925
Average length of the domain: 96.5 aa
Average identity of full alignment: 17 %
Average coverage of the sequence by the domain: 34.63 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 61295632 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 20.7 20.7
Trusted cut-off 20.7 20.7
Noise cut-off 20.6 20.6
Model length: 93
Family (HMM) version: 28
Download: download the raw HMM for this family

Species distribution

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Archea Archea Eukaryota Eukaryota
Bacteria Bacteria Other sequences Other sequences
Viruses Viruses Unclassified Unclassified
Viroids Viroids Unclassified sequence Unclassified sequence

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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 GST_C domain has been found. There are 758 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
A0A044RLF6 View 3D Structure Click here
A0A044RLG3 View 3D Structure Click here
A0A044RLG9 View 3D Structure Click here
A0A044UE17 View 3D Structure Click here
A0A077YXD4 View 3D Structure Click here
A0A077ZC60 View 3D Structure Click here
A0A0B5E2M0 View 3D Structure Click here
A0A0B5E8V1 View 3D Structure Click here
A0A0B5EC24 View 3D Structure Click here
A0A0D2DF47 View 3D Structure Click here
A0A0D2DKU7 View 3D Structure Click here
A0A0D2DUT7 View 3D Structure Click here
A0A0D2E4M1 View 3D Structure Click here
A0A0D2EQW3 View 3D Structure Click here
A0A0D2ES19 View 3D Structure Click here
A0A0D2FAX6 View 3D Structure Click here
A0A0D2G4E3 View 3D Structure Click here
A0A0D2GCJ5 View 3D Structure Click here
A0A0D2GKY9 View 3D Structure Click here
A0A0D2GMS2 View 3D Structure Click here
A0A0D2GQ54 View 3D Structure Click here
A0A0D2GQ99 View 3D Structure Click here
A0A0D2GRJ0 View 3D Structure Click here
A0A0D2GYH4 View 3D Structure Click here
A0A0D2H448 View 3D Structure Click here
A0A0G2JTB1 View 3D Structure Click here
A0A0G2K3C6 View 3D Structure Click here
A0A0H3CDY2 View 3D Structure Click here
A0A0H3GIS7 View 3D Structure Click here
A0A0H3GM02 View 3D Structure Click here
A0A0H3GP63 View 3D Structure Click here
A0A0H3GUF4 View 3D Structure Click here
A0A0H3GYQ8 View 3D Structure Click here
A0A0H3GZ22 View 3D Structure Click here
A0A0K0E3Q2 View 3D Structure Click here
A0A0K0JIJ4 View 3D Structure Click here
A0A0N4U4E0 View 3D Structure Click here
A0A0N4UPV8 View 3D Structure Click here
A0A0P0V328 View 3D Structure Click here
A0A0P0V6Z0 View 3D Structure Click here