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glutathione S-transferase omega 1

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Immunopharmacology Ligand target has curated data in GtoImmuPdb

Target id: 3110

Nomenclature: glutathione S-transferase omega 1

Family: 2.5.1.18 Glutathione transferases

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 241 10q25.1 GSTO1 glutathione S-transferase omega 1
Mouse - 240 19 D1 Gsto1 glutathione S-transferase omega 1
Rat - 241 1q54 Gsto1 glutathione S-transferase omega 1
Gene and Protein Information Comments
Three transcript variants encoding different isoforms are reported for the human gene.
Previous and Unofficial Names Click here for help
GSTO 1-1 | GSTO1-1 | GSTTLp28
Database Links Click here for help
Alphafold
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
Pharos
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia

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Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
C1-27 Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 6.9 pIC50 3
pIC50 6.9 (IC50 1.3x10-7 M) [3]
compound 25 [PMID: 32105470] Small molecule or natural product Immunopharmacology Ligand Hs Inhibition 6.6 pIC50 3
pIC50 6.6 (IC50 2.5x10-7 M) [3]
Description: Enzyme inhibition in a biochemical assay, utilising the substrate S-(4-nitrophenacyl)glutathione (4-NPG) and recombinant GSTO1-1.
Immunopharmacology Comments
GSTO1-1 is reported to act as a NLRP3 inflammasome regulator, via deglutathionylation of NIMA related kinase 7 (NEK7; a NLRP3 inflammasome component [1]). GSTO1-1 inhibition suppresses lipopolysaccharide (LPS)-induced production of proinflammatory cytokines (via TLR4) such as IL-1β, IL-6 and TNF. Thus, GSTO1-1 has potential as a drug target to limit NLRP3-mediated inflammation, and GSTO1-1 inhibitors are being actively pursued for the treatment of inflammatory conditions and pathologies that result from NLRP3 inflammasome activation. To date (March 2020) no GSTO1-1 inhibitors have cleared preclinical development.
Physiological Functions Click here for help
GSTO1-1 deglutathionylates cysteine 253 in NIMA related kinase 7 (NEK7) to promote NLRP3 activation.
Species:  Human
Tissue: 
References:  1
General Comments
Glutathione transferase omega-1 (GSTO1-1) is an omega class cytosolic glutathione transferase (GST). It also exhibits dehydroascorbate reductase, monomethylarsonate reductase, and thioltransferase activities. GSTO1-1 is the only GST to display S-(phenacyl)glutathione reductase and deglutathionylase activities [2].

References

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1. Hughes MM, Hooftman A, Angiari S, Tummala P, Zaslona Z, Runtsch MC, McGettrick AF, Sutton CE, Diskin C, Rooke M et al.. (2019) Glutathione Transferase Omega-1 Regulates NLRP3 Inflammasome Activation through NEK7 Deglutathionylation. Cell Rep, 29 (1): 151-161.e5. [PMID:31577945]

2. Xie Y, Dahlin JL, Oakley AJ, Casarotto MG, Board PG, Baell JB. (2018) Reviewing Hit Discovery Literature for Difficult Targets: Glutathione Transferase Omega-1 as an Example. J Med Chem, 61 (17): 7448-7470. [PMID:29652143]

3. Xie Y, Tummala P, Oakley AJ, Deora GS, Nakano Y, Rooke M, Cuellar ME, Strasser JM, Dahlin JL, Walters MA et al.. (2020) Development of Benzenesulfonamide Derivatives as Potent Glutathione Transferase Omega-1 Inhibitors. J Med Chem, 63 (6): 2894-2914. [PMID:32105470]

How to cite this page

2.5.1.18 Glutathione transferases: glutathione S-transferase omega 1. Last modified on 17/03/2020. Accessed on 27/09/2021. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=3110.