Target Information
| Target General Information | Top | |||||
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| Target ID |
T01521
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| Target Name |
Glutathione S-transferase omega-1 (GSTO-1)
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| Synonyms |
SPG-R; S-(Phenacyl)glutathione reductase; Monomethylarsonic acid reductase; MMA(V) reductase; Glutathione-dependent dehydroascorbate reductase; Glutathione S-transferase omega 1-1; GSTTLP28; GSTO-1; GSTO 1-1
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| Gene Name |
GSTO1
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| Target Type |
Preclinical target
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[1] | ||||
| Disease | [+] 1 Target-related Diseases | + | ||||
| 1 | Solid tumour/cancer [ICD-11: 2A00-2F9Z] | |||||
| Function |
Exhibits glutathione-dependent thiol transferase and dehydroascorbate reductase activities. Has S-(phenacyl)glutathione reductase activity. Has also glutathione S-transferase activity. Participates in the biotransformation of inorganic arsenic and reduces monomethylarsonic acid (MMA) and dimethylarsonic acid.
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| UniProt ID | ||||||
| EC Number |
EC 2.5.1.18
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| Sequence |
MSGESARSLGKGSAPPGPVPEGSIRIYSMRFCPFAERTRLVLKAKGIRHEVININLKNKP
EWFFKKNPFGLVPVLENSQGQLIYESAITCEYLDEAYPGKKLLPDDPYEKACQKMILELF SKVPSLVGSFIRSQNKEDYAGLKEEFRKEFTKLEEVLTNKKTTFFGGNSISMIDYLIWPW FERLEAMKLNECVDHTPKLKLWMAAMKEDPTVSALLTSEKDWQGFLELYLQNSPEACDYG L Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| HIT2.0 ID | T68HNO | |||||
| Drugs and Modes of Action | Top | |||||
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| Preclinical Drug(s) | [+] 1 Preclinical Drugs | + | ||||
| 1 | Piperlongumine | Drug Info | Preclinical | Solid tumour/cancer | [2] | |
| Mode of Action | [+] 1 Modes of Action | + | ||||
| Inhibitor | [+] 1 Inhibitor drugs | + | ||||
| 1 | Piperlongumine | Drug Info | [3] | |||
| 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 | Human Glutathione Transferase Omega1 | PDB:5YVN | ||||
| Method | X-ray diffraction | Resolution | 1.33 Å | Mutation | No | [4] |
| PDB Sequence |
ESARSLGKGS
13 APPGPVPEGS23 IRIYSMRFCP33 FAERTRLVLK43 AKGIRHEVIN53 INLKNKPEWF 63 FKKNPFGLVP73 VLENSQGQLI83 YESAITCEYL93 DEAYPGKKLL103 PDDPYEKACQ 113 KMILELFSKV123 PSLVGSFIRS133 QNKEDYAGLK143 EEFRKEFTKL153 EEVLTNKKTT 163 FFGGNSISMI173 DYLIWPWFER183 LEAMKLNECV193 DHTPKLKLWM203 AAMKEDPTVS 213 ALLTSEKDWQ223 GFLELYLQNS233 PEACDYGL
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: Vitamin C | Ligand Info | |||||
| Structure Description | Human Glutathione Transferase O1-1 C32S Mutant in Complex with Ascorbic Acid | PDB:3VLN | ||||
| Method | X-ray diffraction | Resolution | 1.70 Å | Mutation | Yes | [5] |
| PDB Sequence |
GESARSLGKG
12 SAPPGPVPEG22 SIRIYSMRFS32 PFAERTRLVL42 KAKGIRHEVI52 NINLKNKPEW 62 FFKKNPFGLV72 PVLENSQGQL82 IYESAITCEY92 LDEAYPGKKL102 LPDDPYEKAC 112 QKMILELFSK122 VPSLVGSFIR132 SQNKEDYAGL142 KEEFRKEFTK152 LEEVLTNKKT 162 TFFGGNSISM172 IDYLIWPWFE182 RLEAMKLNEC192 VDHTPKLKLW202 MAAMKEDPTV 212 SALLTSEKDW222 QGFLELYLQN232 SPEACDYGL
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| 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).
Human Similarity Proteins
Human Tissue Distribution
Human Pathway Affiliation
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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 | ||
| 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 | Mechanistic evaluation and transcriptional signature of a glutathione S-transferase omega 1 inhibitor. Nat Commun. 2016 Oct 5;7:13084. | |||||
| REF 2 | Piperlongumine, a potent anticancer phytotherapeutic: Perspectives on contemporary status and future possibilities as an anticancer agent. Pharmacol Res. 2020 Jun;156:104772. | |||||
| REF 3 | Activity-based protein profiling reveals GSTO1 as the covalent target of piperlongumine and a promising target for combination therapy for cancer. Chem Commun (Camb). 2019 Apr 9;55(30):4407-4410. | |||||
| REF 4 | Glutathione transferase Omega 1-1 (GSTO1-1) modulates Akt and MEK1/2 signaling in human neuroblastoma cell SH-SY5Y. Proteins. 2019 Jul;87(7):588-595. | |||||
| REF 5 | Structural insights into the dehydroascorbate reductase activity of human omega-class glutathione transferases. J Mol Biol. 2012 Jul 13;420(3):190-203. | |||||
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