Isozyme-Specific Fluorescent Inhibitor of Glutathione S-Transferase Omega 1
- 5 March 2010
- journal article
- research article
- Published by American Chemical Society (ACS) in ACS Chemical Biology
- Vol. 5 (5), 449-453
- https://doi.org/10.1021/cb100007s
Abstract
Recently, the glutathione S-transferase omega 1 (GSTO1) is suspected to be involved in certain cancers and neurodegenerative diseases. However, profound investigation on the pathological roles of GSTO1 has been hampered by the lack of specific methods to determine or modulate its activity in biological systems containing other isoforms with similar catalytic function. Here, we report a fluorescent compound that is able to inhibit and monitor the activity of GSTO1. We screened 43 fluorescent chemicals and found a compound (6) that binds specifically to the active site of GSTO1. We observed that compound 6 inhibits GSTO1 by covalent modification but spares other isoforms in HEK293 cells and demonstrated that compound 6 could report the activity of GSTO1 in NIH/3T3 or HEK293 cells by measuring the fluorescence intensity of the labeled amount of GSTO1 in SDS−PAGE. Compound 6 is a useful tool to study GSTO1, applicable as a specific inhibitor and an activity reporter.This publication has 17 references indexed in Scilit:
- Diversity-oriented fluorescence library approach for the discovery of sensors and probesMolecular BioSystems, 2009
- Mammalian Cytosolic Glutathione TransferasesCurrent Protein & Peptide Science, 2008
- An Engineered Protein Tag for Multiprotein Labeling in Living CellsChemistry & Biology, 2008
- Polymorphism of glutathione S-transferase Omega gene and risk of cancerCancer Letters, 2006
- Characterization of the monomethylarsonate reductase and dehydroascorbate reductase activities of Omega class glutathione transferase variants: implications for arsenic metabolism and the age-at-onset of Alzheimer's and Parkinson's diseasesPharmacogenetics and Genomics, 2005
- The chemistry and biology of inhibitors and pro-drugs targeted to glutathione S-transferasesCellular and Molecular Life Sciences, 2005
- Characterization of the Omega Class of Glutathione TransferasesMethods in Enzymology, 2005
- The role of glutathione-S-transferase in anti-cancer drug resistanceOncogene, 2003
- Glutathione S-transferase genotypes, genetic susceptibility, and outcome of therapy in childhood acute lymphoblastic leukemiaBlood, 2002
- Laser desorption ionization of proteins with molecular masses exceeding 10,000 daltonsAnalytical Chemistry, 1988