Target Information
| Target General Information | Top | |||||
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| Target ID |
T17221
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| Target Name |
Glutathione S-transferase A1 (GSTA1)
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| Synonyms |
GTH1; GSTA1-1; GST-epsilon; GST class-alpha member 1; GST HA subunit 1; Androst-5-ene-3,17-dione isomerase; 13-hydroperoxyoctadecadienoate peroxidase
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| Gene Name |
GSTA1
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| Target Type |
Literature-reported target
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[1] | ||||
| Function |
Glutathione S-transferase that catalyzes the nucleophilic attack of the sulfur atom of glutathione on the electrophilic groups of a wide range of exogenous and endogenous compounds (Probable). Involved in the formation of glutathione conjugates of both prostaglandin A2 (PGA2) and prostaglandin J2 (PGJ2). It also catalyzes the isomerization of D5-androstene-3,17-dione (AD) into D4-androstene-3,17-dione and may therefore play an important role in hormone biosynthesis. Through its glutathione-dependent peroxidase activity toward the fatty acid hydroperoxide (13S)-hydroperoxy-(9Z,11E)-octadecadienoate/13-HPODE it is also involved in the metabolism of oxidized linoleic acid.
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| UniProt ID | ||||||
| EC Number |
EC 2.5.1.18
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| Sequence |
MAEKPKLHYFNARGRMESTRWLLAAAGVEFEEKFIKSAEDLDKLRNDGYLMFQQVPMVEI
DGMKLVQTRAILNYIASKYNLYGKDIKERALIDMYIEGIADLGEMILLLPVCPPEEKDAK LALIKEKIKNRYFPAFEKVLKSHGQDYLVGNKLSRADIHLVELLYYVEELDSSLISSFPL LKALKTRISNLPTVKKFLQPGSPRKPPMDEKSLEEARKIFRF Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| HIT2.0 ID | T76EHP | |||||
| Cell-based Target Expression Variations | Top | |||||
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| Cell-based Target Expression Variations | ||||||
| Drug Binding Sites of Target | Top | |||||
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| Ligand Name: Glutathione | Ligand Info | |||||
| Structure Description | Crystal structure of hGSTA1-1 complexed with GSH and MPD in each subunit | PDB:6ATO | ||||
| Method | X-ray diffraction | Resolution | 1.55 Å | Mutation | No | [2] |
| PDB Sequence |
AEKPKLHYFN
11 ARGRMESTRW21 LLAAAGVEFE31 EKFIKSAEDL41 DKLRNDGYLM51 FQQVPMVEID 61 GMKLVQTRAI71 LNYIASKYNL81 YGKDIKERAL91 IDMYIEGIAD101 LGEMILLLPV 111 CPPEEKDAKL121 ALIKEKIKNR131 YFPAFEKVLK141 SHGQDYLVGN151 KLSRADIHLV 161 ELLYYVEELD171 SSLISSFPLL181 KALKTRISNL191 PTVKKFLQPG201 SPRKPPMDEK 211 SLEEARKIFR221 F
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: Ethacrynic acid | Ligand Info | |||||
| Structure Description | GLUTATHIONE TRANSFERASE A1-1 COMPLEXED WITH AN ETHACRYNIC ACID GLUTATHIONE CONJUGATE (MUTANT R15K) | PDB:1GSE | ||||
| Method | X-ray diffraction | Resolution | 2.00 Å | Mutation | No | [3] |
| PDB Sequence |
AEKPKLHYFN
11 ARGKMESTRW21 LLAAAGVEFE31 EKFIKSAEDL41 DKLRNDGYLM51 FQQVPMVEID 61 GMKLVQTRAI71 LNYIASKYNL81 YGKDIKERAL91 IDMYIEGIAD101 LGEMILLLPV 111 CPPEEKDAKL121 ALIKEKIKNR131 YFPAFEKVLK141 SHGQDYLVGN151 KLSRADIHLV 161 ELLYYVEELD171 SSLISSFPLL181 KALKTRISNL191 PTVKKFLQPG201 SPRKPPMDEK 211 SLEEARKIFR221 F
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Click to View More Binding Site Information of This Target with Different Ligands | ||||||
| Different Human System Profiles of Target | Top |
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Human Similarity Proteins
of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.
A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs
(Brief Bioinform, 21: 649-662, 2020).
Human Tissue Distribution
of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues.
The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects
(Nat Rev Drug Discov, 20: 64-81, 2021).
Human Pathway Affiliation
of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function.
Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes
(Pharmacol Rev, 58: 259-279, 2006).
Biological Network Descriptors
of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database.
The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information
(Front Pharmacol, 9, 1245, 2018;
Curr Opin Struct Biol. 44:134-142, 2017).
Human Similarity Proteins
Human Tissue Distribution
Human Pathway Affiliation
Biological Network Descriptors
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| Protein Name | Pfam ID | Percentage of Identity (%) | E value |
|---|---|---|---|
| Maleylacetoacetate isomerase (GSTZ1) | 24.870 (48/193) | 3.27E-07 |
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Note:
If a protein has TS (tissue specficity) scores at least in one tissue >= 2.5, this protein is called tissue-enriched (including tissue-enriched-but-not-specific and tissue-specific). In the plots, the vertical lines are at thresholds 2.5 and 4.
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| KEGG Pathway | Pathway ID | Affiliated Target | Pathway Map |
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| Glutathione metabolism | hsa00480 | Affiliated Target |
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| Class: Metabolism => Metabolism of other amino acids | Pathway Hierarchy | ||
| Metabolism of xenobiotics by cytochrome P450 | hsa00980 | Affiliated Target |
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| Class: Metabolism => Xenobiotics biodegradation and metabolism | Pathway Hierarchy | ||
| Drug metabolism - cytochrome P450 | hsa00982 | Affiliated Target |
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| Class: Metabolism => Xenobiotics biodegradation and metabolism | Pathway Hierarchy | ||
| Drug metabolism - other enzymes | hsa00983 | Affiliated Target |
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| Class: Metabolism => Xenobiotics biodegradation and metabolism | Pathway Hierarchy | ||
| Degree | 1 | Degree centrality | 1.07E-04 | Betweenness centrality | 0.00E+00 |
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| Closeness centrality | 1.93E-04 | Radiality | 7.63E-03 | Clustering coefficient | 0.00E+00 |
| Neighborhood connectivity | 3.00E+00 | Topological coefficient | 1.00E+00 | Eccentricity | 2 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| Chemical Structure based Activity Landscape of Target | Top |
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| Target Poor or Non Binders | Top | |||||
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| Target Poor or Non Binders | ||||||
| References | Top | |||||
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| REF 1 | Glutathione S-transferase A1 (GSTA1) as a marker of acetaminophen-induced hepatocyte injury in vitro. Toxicol Mech Methods. 2017 Jul;27(6):401-407. | |||||
| REF 2 | The dynamic nature of hGSTA1-1 C-terminal helix | |||||
| REF 3 | Structural analysis of human alpha-class glutathione transferase A1-1 in the apo-form and in complexes with ethacrynic acid and its glutathione conjugate. Structure. 1995 Jul 15;3(7):717-27. | |||||
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