GGH Human

Gamma-Glutamyl Hydrolase Human Recombinant

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Cat. No.

BT28144

Source

E.coli.

Synonyms

Gamma-glutamyl hydrolase (conjugase, folylpolygammaglutamyl hydrolase), Gamma-Glu-X carboxypeptidase, gamma-glutamyl hydrolase, Conjugase, GH, EC 3.4.19.9.

Appearance

Sterile Filtered colorless solution.

Purity

Greater than 95% 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.

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Description

Biochemical Function

GGH hydrolyzes poly-γ-glutamyl chains from folates and antifolates, influencing their bioavailability and retention. Key roles include:

Folate metabolism: Converts dietary folylpolyglutamates to monoglutamates for cellular uptake .
Antifolate activation: Modulates polyglutamylation of drugs like methotrexate (MTX), affecting their cytotoxicity .

Research Findings on GGH Modulation

Studies using HCT116 colon and MDA-MB-435 breast cancer models reveal critical insights:

Table 1: Effects of GGH Overexpression vs. Inhibition

Parameter	GGH Overexpression	GGH Inhibition
GGH Activity	↑ 2–3 fold	↓ 70–80%
Intracellular Folate	↓ 20–30%	↑ 40–50%
TS Activity	↓ 25–35%	↑ 15–25%
DHFR Activity	↓ 20–30%	↑ 20–30%
Global DNA Methylation	↓ 16–22%	↑ 7–15%

Key Observations:

Chemosensitivity:
- GGH overexpression reduces MTX efficacy at physiological folate levels (2.3 μM folic acid) .
- Paradoxically, GGH inhibition decreases chemosensitivity to MTX under low folate conditions (50–100 nM 5-MTHF) .
Cell Proliferation:
- Overexpression slows growth due to folate depletion .
- Inhibition accelerates proliferation in folate-replete environments .

Clinical Implications

Cancer Prognosis: High GGH expression correlates with poor outcomes in ERG-negative prostate cancer .
Epigenetic Effects: GGH modulation alters DNA methylation patterns, influencing gene expression in pathways like cell cycle regulation and lipid metabolism .

Therapeutic Relevance

GGH’s role in folate and antifolate metabolism positions it as a potential target for:

Chemotherapy Optimization: Enhancing polyglutamylation of antifolates (e.g., 5-FU) via GGH inhibition could improve drug retention .
Epigenetic Therapies: Modulating GGH activity may correct aberrant DNA methylation in cancers .

Product Specs

Introduction

Gamma-glutamyl hydrolase (GGH) is a dimeric enzyme responsible for hydrolyzing the gamma-glutamyl chain found in folylpoly-gamma-glutamyl substrates. This enzyme plays a critical role in the metabolism of folyl and antifolyl poly-gamma-glutamates, impacting the bioavailability of pteroylpolyglutamates obtained from dietary sources and the processing of both antifolates and pteroylpolyglutamates.

Description

Recombinant human GGH, produced in E. coli, is a single, non-glycosylated polypeptide chain comprising 315 amino acids (residues 25-318) with a molecular weight of 35.9 kDa. This protein includes a 21 amino acid His-tag fused at the N-terminus and is purified using proprietary chromatographic methods.

Physical Appearance

Clear, colorless solution, sterile-filtered.

Formulation

The GGH solution is provided at a concentration of 0.5 mg/ml in a buffer containing 20 mM Tris-HCl (pH 8.0), 100 mM NaCl, 1 mM DTT, and 10% glycerol.

Stability

For short-term storage (up to 2-4 weeks), the solution can be stored at 4°C. For extended storage, freeze the solution at -20°C. Adding a carrier protein (0.1% HSA or BSA) is recommended for long-term storage. Avoid repeated freezing and thawing cycles.

Purity

The purity is determined to be greater than 95% via SDS-PAGE analysis.

Synonyms

Gamma-glutamyl hydrolase (conjugase, folylpolygammaglutamyl hydrolase), Gamma-Glu-X carboxypeptidase, gamma-glutamyl hydrolase, Conjugase, GH, EC 3.4.19.9.

Source

E.coli.

Amino Acid Sequence

MGSSHHHHHH SSGLVPRGSH MRPHGDTAKK PIIGILMQKC RNKVMKNYGR YYIAASYVKY LESAGARVVP VRLDLTEKDY EILFKSINGI LFPGGSVDLR RSDYAKVAKI FYNLSIQSFD DGDYFPVWGT CLGFEELSLL ISGECLLTAT DTVDVAMPLN FTGGQLHSRM FQNFPTELLL SLAVEPLTAN FHKWSLSVKN FTMNEKLKKF FNVLTTNTDG KIEFISTMEG YKYPVYGVQW HPEKAPYEWK NLDGISHAPN AVKTAFYLAE FFVNEARKNN HHFKSESEEE KALIYQFSPI YTGNISSFQQ CYIFD

Product Science Overview

Structure and Expression

The human recombinant form of GGH is typically expressed in host cells such as HEK293 or E. coli. The recombinant protein often includes a polyhistidine tag (His-tag) to facilitate purification. For example, a recombinant human GGH protein expressed in HEK293 cells consists of 305 amino acids and has a predicted molecular mass of approximately 35.1 kDa. Another variant expressed in E. coli includes a His-tag at the N-terminus and corresponds to amino acids 25-318 of the human GGH.

Function and Importance

GGH is a homodimeric protein that catalyzes the cleavage of the gamma-glutamyl chain of folylpoly-gamma-glutamyl substrates. This activity is central to the metabolism of folyl and antifolyl poly-gamma-glutamates. By regulating intracellular folate levels, GGH ensures proper cell proliferation and DNA synthesis. Additionally, GGH plays a role in the bioavailability of dietary pteroylpolyglutamates and the metabolism of antifolates such as methotrexate (MTX), which are used in chemotherapy .

Clinical Relevance

GGH’s role in folate metabolism makes it a significant enzyme in various physiological and pathological processes. For instance, cytoplasmic GGH has been implicated in the development and progression of invasive breast cancer. Understanding the function and regulation of GGH can provide insights into cancer biology and potential therapeutic targets.

Stability and Storage

Recombinant GGH proteins are typically lyophilized and shipped at ambient temperature. They are stable for up to twelve months when stored at -20°C to -80°C under sterile conditions. It is recommended to aliquot the protein to avoid repeated freeze-thaw cycles.

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GGH Human

Description

Biochemical Function

Research Findings on GGH Modulation

Table 1: Effects of GGH Overexpression vs. Inhibition

Key Observations:

Clinical Implications

Therapeutic Relevance

Product Specs

Product Science Overview

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