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Drug Metabolism Letters

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ISSN (Print): 1872-3128
ISSN (Online): 1874-0758

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Short Communication

The Catalytic Activity of GSTM1 In vitro is Independent of MAPK8

Author(s): Shannon Robin, Khalil Ben Hassine, Simona Jurkovic Mlakar, Vid Mlakar, Marc Ansari* and Chakradhara Rao S. Uppugunduri*

Volume 14, Issue 3, 2021

Published on: 17 December, 2021

Page: [163 - 165] Pages: 3

DOI: 10.2174/1872312814666211122164456

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Abstract

Background: Glutathione S-transferases (GSTs) are phase II metabolic enzymes crucial for the metabolism of electrophilic drugs. Additionally, several GST isoforms are involved in protein- protein interaction with mitogen-activated protein kinases (MAPKs), modulating apoptosis pathways.

Methods: To assess the potential change of enzymatic activity, we performed a GST enzyme assay with human recombinant GSTM1 in the presence and absence of MAPK8. Recently, GSTM1 has been demonstrated to interact with MAPK8 both in silico and in vitro. The binding interface predicted in silico comprised amino acid residues present on the surface of the protein and a few were deep in the active site of the protein.

Results: The experiment demonstrated that the GSTM1 activity was conserved even in the presence of MAPK8 in the assay.

Conclusion: The possible alteration in the activity of MAPK8 in this interaction needs to be evaluated in further experiments.

Keywords: Mitogen-activated protein kinase 8 (MAPK8), glutathione s-transferase mu-1 (GSTM1), protein-protein interaction, GST enzyme assay, CDNB, inhibition.

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[1]
Townsend, D.M.; Tew, K.D. The role of glutathione-S-transferase in anti-cancer drug resistance. Oncogene, 2003, 22(47), 7369-7375.
[http://dx.doi.org/10.1038/sj.onc.1206940] [PMID: 14576844]
[2]
Cho, S.G.; Lee, Y.H.; Park, H.S.; Ryoo, K.; Kang, K.W.; Park, J.; Eom, S.J.; Kim, M.J.; Chang, T.S.; Choi, S.Y.; Shim, J.; Kim, Y.; Dong, M.S.; Lee, M.J.; Kim, S.G.; Ichijo, H.; Choi, E.J. Glutathione S-transferase mu modulates the stress-activated signals by suppressing apoptosis signal-regulating kinase 1. J. Biol. Chem., 2001, 276(16), 12749-12755.
[http://dx.doi.org/10.1074/jbc.M005561200] [PMID: 11278289]
[3]
Uppugunduri, C.R.S.; Muthukumaran, J.; Robin, S.; Santos-Silva, T.; Ansari, M. In silico and in vitro investigations on the protein-protein interactions of glutathione S-transferases with mitogen-activated protein kinase 8 and apoptosis signal-regulating kinase 1. J. Biomol. Struct. Dyn., 2020, 30, 1-11.
[http://dx.doi.org/10.1080/07391102.2020.1827036] [PMID: 32996404]
[4]
Patskovsky, Y.; Patskovska, L.; Almo, S.C.; Listowsky, I. Transition state model and mechanism of nucleophilic aromatic substitution reactions catalyzed by human glutathione S-transferase M1a-1a. Biochemistry, 2006, 45(12), 3852-3862.
[http://dx.doi.org/10.1021/bi051823+] [PMID: 16548513]
[5]
Habig, W.H.; Pabst, M.J.; Jakoby, W.B. Glutathione S-transferases. The first enzymatic step in mercapturic acid formation. J. Biol. Chem., 1974, 249(22), 7130-7139.
[http://dx.doi.org/10.1016/S0021-9258(19)42083-8] [PMID: 4436300]
[6]
Robin, S.K.D.; Ansari, M.; Uppugunduri, C.R.S. Spectrophotometric screening for potential inhibitors of cytosolic glutathione s- transferases. J. Vis. Exp., 2020, 164(164), e61347.
[http://dx.doi.org/10.3791/61347] [PMID: 33104076]
[7]
Klaus, A.; Zorman, S.; Berthier, A.; Polge, C.; Ramirez, S.; Michelland, S.; Sève, M.; Vertommen, D.; Rider, M.; Lentze, N.; Auerbach, D.; Schlattner, U. Glutathione S-transferases interact with AMP-activated protein kinase: evidence for S-glutathionylation and activation in vitro. PLoS One, 2013, 8(5), e62497.
[http://dx.doi.org/10.1371/journal.pone.0062497] [PMID: 23741294]

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