GCLM Human

Glutamate-Cysteine Ligase, Modifier Subunit Human Recombinant
Cat. No.
BT4779
Source
Escherichia Coli.
Synonyms
Glutamate--cysteine ligase regulatory subunit, GCS light chain, Gamma-ECS regulatory subunit, Gamma-glutamylcysteine synthetase regulatory subunit, Glutamate--cysteine ligase modifier subunit, GCLM, GLCLR.
Appearance
Sterile Filtered colorless solution.
Purity
Greater than 90.0% as determined by SDS-PAGE.
Usage
THE BioTek's products are furnished for LABORATORY RESEARCH USE ONLY. The product may not be used as drugs, agricultural or pesticidal products, food additives or household chemicals.
Shipped with Ice Packs
In Stock

Description

GCLM Human Recombinant produced in E. coli is a single polypeptide chain containing 298 amino acids (1-274) and having a molecular mass of 33.3kDa.
GCLM is fused to a 24 amino acid His-tag at N-terminus & purified by proprietary chromatographic techniques.

Product Specs

Introduction
Glutamate-cysteine ligase (GCLM) is the initial rate-limiting enzyme involved in glutathione biosynthesis. This enzyme comprises two subunits: a heavier catalytic subunit and a lighter regulatory subunit. Deficiencies in GCLM have been linked to certain types of hemolytic anemia.
Description
Recombinant human GCLM, produced in E. coli, is a single polypeptide chain consisting of 298 amino acids (residues 1-274) with a molecular weight of 33.3kDa. This protein includes a 24 amino acid His-tag fused to the N-terminus and is purified using proprietary chromatographic techniques.
Physical Appearance
A clear, sterile-filtered solution.
Formulation
The GCLM solution is provided at a concentration of 1mg/ml in a buffer consisting of 20mM Tris-HCl (pH 8.0), 10% glycerol, and 0.15M NaCl.
Stability
For short-term storage (2-4 weeks), the product can be stored at 4°C. For longer storage, it is recommended to freeze the product at -20°C. To ensure optimal stability during long-term storage, adding a carrier protein such as 0.1% HSA or BSA is advised. Repeated freezing and thawing should be avoided.
Purity
The purity of this product is greater than 90.0% as determined by SDS-PAGE analysis.
Synonyms
Glutamate--cysteine ligase regulatory subunit, GCS light chain, Gamma-ECS regulatory subunit, Gamma-glutamylcysteine synthetase regulatory subunit, Glutamate--cysteine ligase modifier subunit, GCLM, GLCLR.
Source
Escherichia Coli.
Amino Acid Sequence
MGSSHHHHHH SSGLVPRGSH MGSHMGTDSR AAKALLARAR TLHLQTGNLL NWGRLRKKCP STHSEELHDC IQKTLNEWSS QINPDLVREF PDVLECTVSH AVEKINPDER EEMKVSAKLF IVESNSSSST RSAVDMACSV LGVAQLDSVI IASPPIEDGV NLSLEHLQPY WEELENLVQS KKIVAIGTSD LDKTQLEQLY QWAQVKPNSN QVNLASCCVM PPDLTAFAKQ FDIQLLTHND PKELLSEASF QEALQESIPD IQAHEWVPLW LLRYSVIVKS RGIIKSKGYI LQAKRRGS.

Product Science Overview

Introduction

Glutamate-Cysteine Ligase (GCL) is a critical enzyme in the biosynthesis of glutathione (GSH), a major antioxidant that protects cells from oxidative stress. GCL is composed of two subunits: the catalytic subunit (GCLC) and the modifier subunit (GCLM). The modifier subunit, also known as the Glutamate-Cysteine Ligase Modifier Subunit (GCLM), plays a crucial role in regulating the activity of the catalytic subunit.

Structure and Function

GCLM is a protein coding gene that encodes the modifier subunit of the enzyme glutamate-cysteine ligase. The GCLM protein itself does not possess enzymatic activity but enhances the catalytic efficiency of the GCLC when they form a holoenzyme complex . The GCLM subunit is approximately 31 kDa in size and is essential for the proper functioning of the GCL enzyme .

Role in Glutathione Biosynthesis

Glutathione is synthesized in a two-step process, with GCL catalyzing the first and rate-limiting step. This step involves the ATP-dependent condensation of glutamate and cysteine to form gamma-glutamylcysteine (γ-GC) . The presence of GCLM increases the affinity of GCLC for its substrates and enhances the overall catalytic activity of the enzyme .

Biological Significance

GCLM is critical for maintaining cellular redox balance and protecting cells from oxidative damage. Dysregulation of GCLM and GCL activity has been implicated in various human diseases, including diabetes, Parkinson’s disease, Alzheimer’s disease, chronic obstructive pulmonary disease (COPD), HIV/AIDS, and cancer . In cancer, increased expression and activity of GCLM and GCL support high levels of cell proliferation and confer resistance to many chemotherapeutic agents .

Genetic and Molecular Aspects

The GCLM gene is located on chromosome 1 and is subject to alternative splicing, resulting in multiple transcript variants encoding different isoforms . The gene is regulated at multiple levels, including transcriptional, post-transcriptional, and post-translational modifications . Genetic knockdown of GCLM results in embryonic lethality, highlighting its essential role in cellular function .

Clinical Implications

Given its pivotal role in glutathione biosynthesis, GCLM is a potential therapeutic target for modulating cellular antioxidant capacity. Strategies to enhance or inhibit GCLM activity could have significant implications for treating diseases associated with oxidative stress and glutathione dysregulation .

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