The Catalytic Activity of GSTM1 In vitro is Independent of MAPK8.

Drug metabolism letters Pub Date : 2021-01-01 DOI:10.2174/1872312814666211122164456

Shannon Robin, Khalil Ben Hassine, Simona Jurkovic Mlakar, Vid Mlakar, Marc Ansari, Chakradhara Rao S Uppugunduri

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引用次数: 1

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.

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GSTM1的体外催化活性不依赖于MAPK8。

背景:谷胱甘肽s -转移酶(GSTs)是亲电药物代谢的关键II期代谢酶。此外，几种GST亚型参与与丝裂原活化蛋白激酶(MAPKs)的蛋白-蛋白相互作用，调节细胞凋亡途径。方法:为了评估酶活性的潜在变化，我们用人重组GSTM1在MAPK8存在和不存在的情况下进行了GST酶测定。最近，GSTM1已被证明在硅和体外与MAPK8相互作用。用硅预测的结合界面由存在于蛋白质表面的氨基酸残基组成，少数氨基酸残基位于蛋白质的活性位点深处。结果:实验表明，即使在MAPK8存在的情况下，GSTM1的活性仍保持不变。结论:在这种相互作用中，MAPK8活性的可能改变需要进一步的实验来评估。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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Drug metabolism letters Pharmacology, Toxicology and Pharmaceutics-Pharmaceutical Science

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期刊介绍： Drug Metabolism Letters publishes letters and research articles on major advances in all areas of drug metabolism and disposition. The emphasis is on publishing quality papers very rapidly by taking full advantage of the Internet technology both for the submission and review of manuscripts. The journal covers the following areas: In vitro systems including CYP-450; enzyme induction and inhibition; drug-drug interactions and enzyme kinetics; pharmacokinetics, toxicokinetics, species scaling and extrapolations; P-glycoprotein and transport carriers; target organ toxicity and interindividual variability; drug metabolism and disposition studies; extrahepatic metabolism; phase I and phase II metabolism; recent developments for the identification of drug metabolites.