GSTM2 Human

Glutathione S-Transferase MU 2 Human Recombinant
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Description

Molecular Structure and Gene Characteristics

Gene Details:

  • Symbol: GSTM2

  • Chromosomal Location: 1p13.3 (organized within a GST mu-class gene cluster) .

  • Protein Class: Glutathione transferase (Mu class) .

  • Isoforms: Encodes a 218-amino acid protein with a molecular weight of ~27.9 kDa .

Structural Features:

  • Predicted to adopt a thioredoxin fold, common among GSTs, with a glutathione-binding site and hydrophobic substrate-binding domain .

  • Purified recombinant GSTM2 is produced in E. coli as a His-tagged protein, stable in Tris-HCl buffer with glycerol and DTT .

Table 1: Biophysical Properties of Recombinant GSTM2

PropertyDetail
Molecular Weight27.9 kDa
Expression SystemEscherichia coli
Storage Conditions4°C (short-term), -20°C (long-term)
Buffer Composition20 mM Tris-HCl, 10% glycerol, 0.1M NaCl, 1 mM DTT

Primary Functions:

  • Detoxification: Conjugates glutathione to electrophilic compounds (e.g., carcinogens, environmental toxins) for excretion .

  • Oxidative Stress Response: Neutralizes reactive oxygen species (ROS) and lipid peroxidation byproducts .

Emerging Roles:

  • Hepatic Steatosis Regulation:

    • Inhibits fat accumulation in the liver by binding apoptosis signal-regulating kinase 1 (ASK1), suppressing p38-JNK signaling .

    • Overexpression in mice reduces lipid droplets and reverses methionine-choline-deficient diet (MCDD)-induced steatosis .

  • Immune Modulation in Cancer:

    • Downregulated in colon cancer, correlating with poor prognosis and altered immune cell infiltration (e.g., reduced CD8+ T cells, macrophages) .

    • Associated with microsatellite instability (MSI), influencing immunotherapy efficacy .

Disease Associations:

  • Non-Alcoholic Fatty Liver Disease (NAFLD):

    • GSTM2-null mice exhibit exacerbated hepatic steatosis, while overexpression mitigates lipid accumulation .

  • Cancer:

    • Colon Cancer: Low GSTM2 expression correlates with advanced stages, lymph node metastasis, and shorter survival .

    • Pancreatic and Prostate Cancer: Reduced expression linked to chemoresistance and tumor progression .

Table 2: Clinical Correlations of GSTM2 Dysregulation

ConditionExpression PatternClinical Impact
Hepatic SteatosisUpregulatedProtective against lipid accumulation
Colon CancerDownregulatedPoor prognosis, immune evasion
Neurodegenerative DiseasesPolymorphismsIncreased susceptibility

Key Studies:

  1. Hepatic Steatosis (2022):

    • GSTM2 knockout mice showed 40% higher hepatic triglycerides versus wild-type. Overexpression reduced ASK1 phosphorylation by 60% .

  2. Colon Cancer Immune Microenvironment (2022):

    • GSTM2 expression positively correlated with B cell, CD8+ T cell, and macrophage infiltration (p < 0.001) .

    • Low GSTM2 linked to 2.5-fold higher mortality risk in a Chinese cohort (n = 174) .

Mechanistic Insights:

  • ASK1-p38/JNK Pathway: GSTM2 binds ASK1, reducing phosphorylation by 70% and downstream pro-inflammatory signaling .

  • Immune Pathways: Enriched in chemokine signaling, leukocyte migration, and adaptive immune response via gene set enrichment analysis (GSEA) .

Therapeutic Potential

  • NAFLD/NASH: Gene therapy targeting GSTM2 overexpression could mitigate steatosis and inflammation .

  • Cancer Immunotherapy: Restoring GSTM2 expression may enhance immune cell infiltration and response to checkpoint inhibitors .

  • Biomarker Utility: Low GSTM2 mRNA levels in blood or tissue could serve as a prognostic marker for liver/metabolic diseases and cancer .

Genetic Variants and Polymorphisms

  • The GSTM2 locus is highly polymorphic, influencing detoxification capacity and drug metabolism (e.g., chemotherapeutic agents) .

  • Specific variants are associated with altered risks for cardiovascular diseases and neurodegeneration .

Expression and Distribution

  • Tissue Specificity: Highly expressed in the liver, kidney, and adrenal glands .

  • Subcellular Localization: Primarily cytosolic, with minor mitochondrial associations .

Product Specs

Introduction
Glutathione S-transferase Mu 2 (GSTM2) is a member of the glutathione s-transferase (GST) protein family. These enzymes play a crucial role in detoxification by catalyzing the conjugation of glutathione with electrophilic compounds, including carcinogens, drugs, toxins, and oxidative stress byproducts. GSTM2, belonging to the mu class, is one of eight GST families (alpha, kappa, mu, omega, pi, sigma, theta, zeta). Genes encoding the mu class enzymes are located on chromosome 1p13.3 and exhibit high polymorphism. This genetic variation influences individual susceptibility to carcinogens and toxins, impacting the toxicity and efficacy of certain drugs.
Description
Recombinant human GSTM2, expressed in E. coli, is a purified protein with a His tag. This non-glycosylated polypeptide chain comprises 238 amino acids (with the His tag at the N-terminus) and has a molecular weight of 27.9kDa. The purification process employs proprietary chromatographic techniques.
Physical Appearance
Clear, colorless solution that has been sterilized by filtration.
Formulation
The GSTM2 solution is supplied at a concentration of 0.5mg/ml in a buffer consisting of 20mM Tris-HCl (pH 8.0), 10% glycerol, 0.1M NaCl, and 1mM DTT.
Stability
For short-term storage (2-4 weeks), the GSTM2 solution can be kept at 4°C. For extended storage, freeze the solution at -20°C. Adding a carrier protein like HSA or BSA (0.1%) is recommended for long-term storage. Minimize repeated freeze-thaw cycles.
Purity
The purity of GSTM2 is greater than 95% as assessed by SDS-PAGE analysis.
Biological Activity
GSTM2 exhibits a specific activity of less than 25 units/mg. One unit of activity refers to the enzyme's ability to conjugate 1.0 µmole of 1-chloro-2,4-dinitrobenzene (CDNB) with reduced glutathione per minute at a pH of 6.5 and a temperature of 25°C.
Synonyms
Glutathione S-transferase Mu 2, GST class-mu 2, GSTM2-2, GSTM2, GST4, GSTM, GTHMUS, MGC117303.
Source
Escherichia Coli.
Amino Acid Sequence
MGSSHHHHHH SSGLVPRGSH MPMTLGYWNI RGLAHSIRLL LEYTDSSYEE KKYTMGDAPD YDRSQWLNEK FKLGLDFPNL PYLIDGTHKI TQSNAILRYI ARKHNLCGES EKEQIREDIL ENQFMDSRMQ LAKLCYDPDF EKLKPEYLQA LPEMLKLYSQ FLGKQPWFLG DKITFVDFIA YDVLERNQVF EPSCLDAFPN LKDFISRFEG LEKISAYMKS SRFLPRPVFT KMAVWGNK.

Product Science Overview

Introduction

Glutathione S-Transferase Mu 2 (GSTM2) is a member of the glutathione S-transferase (GST) family, which plays a crucial role in the detoxification of endogenous and exogenous compounds. GSTM2 is involved in the conjugation of reduced glutathione to a wide variety of hydrophobic and electrophilic compounds, facilitating their excretion from the body.

Structure and Function

GSTM2 is a protein-coding gene that encodes for the enzyme glutathione S-transferase Mu 2. This enzyme is part of the larger GST superfamily, which is divided into several classes, including Alpha, Mu, Pi, and Theta. The Mu class, to which GSTM2 belongs, is characterized by its ability to conjugate glutathione to a variety of substrates, including carcinogens, therapeutic drugs, and products of oxidative stress .

The primary function of GSTM2 is to catalyze the conjugation of glutathione to electrophilic compounds, thereby neutralizing their reactivity and facilitating their excretion. This process is essential for cellular detoxification and protection against oxidative stress. GSTM2 is also involved in the metabolism of various xenobiotics and endogenous compounds, contributing to the overall detoxification capacity of the cell .

Biological Significance

GSTM2 plays a significant role in protecting cells from oxidative damage and maintaining cellular homeostasis. It is expressed in various tissues, including the liver, where it contributes to the detoxification of harmful compounds. The enzyme’s activity is crucial for the metabolism of drugs and the detoxification of reactive oxygen species (ROS), which can cause cellular damage if not properly managed .

In addition to its detoxification role, GSTM2 has been implicated in various diseases. For instance, alterations in GSTM2 expression have been associated with an increased risk of certain cancers, including colon adenocarcinoma . The enzyme’s role in detoxifying carcinogens suggests that it may have a protective effect against cancer development. Furthermore, GSTM2 has been linked to other conditions, such as autism spectrum disorder and cranioectodermal dysplasia .

Clinical Applications

Recombinant human GSTM2 has been utilized in various research and clinical applications. The recombinant form of the enzyme is produced using genetic engineering techniques, allowing for the study of its structure, function, and potential therapeutic uses. Recombinant GSTM2 is often used in biochemical assays to investigate its role in detoxification processes and its interactions with other molecules .

In clinical research, GSTM2 has been studied for its potential as a biomarker for certain diseases. For example, changes in GSTM2 expression levels have been investigated as potential indicators of cancer risk and progression . Additionally, the enzyme’s role in drug metabolism makes it a target for studying drug interactions and potential adverse effects.

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