Summary: Glutathione S-transferase, N-terminal domain
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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
- hGST5.8 (putative)
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.
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Glutathione S-transferase, N-terminal domain Provide feedback
Function: conjugation of reduced glutathione to a variety of targets. Also included in the alignment, but not GSTs: S-crystallins from squid (similarity to GST previously noted); eukaryotic elongation factors 1-gamma (not known to have GST activity and similarity not previously recognised); HSP26 family of stress-related proteins including auxin-regulated proteins in plants and stringent starvation proteins in E. coli (not known to have GST activity and similarity not previously recognised). The glutathione molecule binds in a cleft between the N- and C-terminal domains - the catalytically important residues are proposed to reside in the N-terminal domain .
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
Internal database links
|SCOOP:||Glrx-like Glutaredoxin GST_C GST_C_2 GST_N_2 GST_N_3 GST_N_4 GST_N_5 PPTA Thioredoxin_3 Tom37|
|Similarity to PfamA using HHSearch:||Glutaredoxin GST_N_2 GST_N_3 GST_N_4 GST_N_5|
External database links
This tab holds annotation information from the InterPro database.
InterPro entry IPR004045
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 Cephalopoda 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.
Soluble GSTs activate glutathione (GSH) to GS-. In many GSTs, this is accomplished by a Tyr at H-bonding distance from the sulphur of GSH. These enzymes catalyse nucleophilic attack by reduced glutathione (GSH) on nonpolar compounds that contain an electrophilic carbon, nitrogen, or sulphur atom [ PUBMED:16399376 ].
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, with each monomer composed of two distinct domains [ PUBMED:12211029 ]. The N-terminal domain forms a thioredoxin-like fold that binds the glutathione moiety, while the C-terminal domain contains several hydrophobic alpha-helices that specifically bind hydrophobic substrates.
This entry represents the N-terminal domain of GST.
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
|Molecular function||protein binding (GO:0005515)|
|Biological process||glutathione metabolic process (GO:0006749)|
Below is a listing of the unique domain organisations or architectures in which this domain is found. More...
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This clan contains families related to the thioredoxin family. Thioredoxins are small enzymes that are involved in redox reactions via the reversible oxidation of an active centre disulfide bond. The thioredoxin fold consists of a 3 layer alpha/beta/alpha sandwich and a central beta sheet.
The clan contains the following 65 members:2Fe-2S_thioredx AhpC-TSA AhpC-TSA_2 ArsC ArsD Calsequestrin DIM1 DSBA DUF1223 DUF1462 DUF1525 DUF1687 DUF2703 DUF2847 DUF4174 DUF6436 DUF6568 DUF899 DUF929 DUF953 ERp29_N GILT Glrx-like Glutaredoxin GSHPx GST_N GST_N_2 GST_N_3 GST_N_4 GST_N_5 HyaE KaiB L51_S25_CI-B8 MRP-S23 MRP-S25 OST3_OST6 Phe_hydrox_dim Phosducin QSOX_Trx1 Rdx Redoxin SCO1-SenC SelP_N Sep15_SelM SH3BGR T4_deiodinase Thioredox_DsbH Thioredoxin Thioredoxin_11 Thioredoxin_12 Thioredoxin_13 Thioredoxin_14 Thioredoxin_15 Thioredoxin_16 Thioredoxin_2 Thioredoxin_3 Thioredoxin_4 Thioredoxin_5 Thioredoxin_6 Thioredoxin_7 Thioredoxin_8 Thioredoxin_9 Tom37 TraF YtfJ_HI0045
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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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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.
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|Author:||Eddy SR , Griffiths-Jones SR|
|Number in seed:||22|
|Number in full:||34909|
|Average length of the domain:||74.3 aa|
|Average identity of full alignment:||25 %|
|Average coverage of the sequence by the domain:||30.93 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 61295632 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||23|
|Download:||download the raw HMM for this family|
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Unmapped species names
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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Since we reduce the species tree to only the eight main taxonomic levels, sequences that are mapped to the sub-species level in the tree would not normally be shown. Rather than leave out these species, we map them instead to their parent species. So, for example, for sequences belonging to one of the Vibrio cholerae sub-species in the NCBI taxonomy, we show them instead as belonging to the species Vibrio cholerae.
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The tree shows the occurrence of this domain across different species. More...
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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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Finally, we group sequences from the same organism according to the NCBI code that is assigned by UniProt, allowing us to count the number of distinct sequences on which the domain is found. This value is shown in the pink boxes.
We use the NCBI species tree to group organisms according to their taxonomy and this forms the structure of the displayed tree. Note that in some cases the trees are too large (have too many nodes) to allow us to build an interactive tree, but in most cases you can still view the tree in a plain text, non-interactive representation. Those species which are represented in the seed alignment for this domain are highlighted.
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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_N domain has been found. There are 1199 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.