TtGSTm34-8xHis Enzyme Substrate Affinity and Stability

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Solution Overview

Problem

Existing GST enzymes have limitations in terms of affinity for substrates and stability under various conditions, which affects their efficiency in enzyme kinetics and affinity purification processes.

Innovation Solution

The development of a recombinant Tetrahymena thermophila Glutathione S Transferase Mu34 (TtGSTm34-8xHis) enzyme, which includes an 8xHis tag and is produced in Tetrahymena thermophila, offering high affinity for substrates and improved stability.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If commercially available GST enzymes are used, then enzyme kinetics and affinity purification processes can be performed, but the affinity for substrates is insufficient and stability under various conditions is poor

Engineering Contradiction:
ImprovestabilityVSAvoidenzyme production complexity
Core Design Contradiction:
ReliabilityVSEase of manufacture

Solution Approach 1:

The patent segments the GST enzyme production by using a specific isoform (GSTm34) from Tetrahymena thermophila with an 8xHis tag, separating the catalytic domain from other GST isoforms to achieve both high stability and substrate affinity while maintaining ease of production through targeted recombinant expression

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent changes the kinetic parameters of the enzyme by selecting a specific GST isoform (GSTm34) that exhibits superior substrate affinity (low Km value) and stability characteristics compared to commercial GST enzymes, thereby improving reliability without increasing manufacturing complexity

Inventive Principle:
Principle #35Parameter changes

2Measurement precision

If existing GST enzymes are used, then basic enzyme kinetics can be studied, but the affinity for substrates such as glutathione is insufficient

Engineering Contradiction:
Improvesubstrate affinityVSAvoidreaction rate
Core Design Contradiction:
Measurement precisionVSProductivity

Solution Approach 1:

The patent improves measurement precision by utilizing GSTm34's optimized kinetic parameters, specifically its low Km value for glutathione (0.54 mM), which indicates high substrate affinity and enables more precise enzymatic measurements while maintaining high reaction rates through the enzyme's catalytic efficiency

Inventive Principle:
Principle #35Parameter changes

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

The TtGSTm34-8xHis enzyme demonstrates high affinity for glutathione with a low K m value of 0.54 mM, enhanced stability, and improved performance in enzyme kinetics and affinity purification, surpassing commercially available GST enzymes.

Implementation Method 1

GSTs catalyze the reaction of substrate glutathione with electrophiles of both endogenous and xenobiotic origins

Methodology Applied
Scientific EffectEnzyme catalysis: Enzyme

Implementation Method 2

By conjugating glutathione with toxic electrophilic substrates, GSTs give rise to less reactive and more soluble products

Methodology Applied
Scientific EffectConjugation reaction: Chemical Bonding

Implementation Method 3

His-tag (Polyhistidine-tag) is another widely used affinity tag. It can be defined as an amino acid motif in proteins that consists of at least six histidine (His) amino acids

Methodology Applied
Scientific EffectAffinity binding: Adsorption

Data Source

PatentEP3856897B1Recombinant tetrahymena thermophila glutathione s transferase mu34 enzyme (ttgstm34-8xhis) and uses thereof
Publication Date: 2025.01.22 ANADOLU UNIVSI
  • EP3856897B1 patent drawingFigure 1A~1C
  • EP3856897B1 patent drawingFigure 2~3
  • EP3856897B1 patent drawingFigure 4

AI summary

The present invention relates to the recombinant GST enzyme that is produced in the organism Tetrahymena thermophila. More specifically, the present invention relates to TtGSTm34-8xHis enzyme and uses thereof.