Identification of novel glutathione transferases and polymorphic variants by expressed sequence tag database analysis

Area of Science:

• Genomics
• Biochemistry
• Pharmacogenetics

Background:

• The expressed sequence tag (EST) database facilitates gene discovery through sequence alignment.
• The glutathione S-transferase (GST) superfamily is crucial for biotransformation and detoxification.
• Identifying novel gene families and allelic variants is essential for understanding genetic diversity.

Framework:

• Utilized sequence alignment strategies to search the human EST database.
• Focused on the glutathione S-transferase (GST) super family for gene discovery.
• Identified the Zeta class of GSTs and their enzymatic functions.

Implementation:

• Characterized the catalytic activity of Zeta class GSTs in alpha-haloacid biotransformation and maleylacetoacetic acid isomerization.
• Discovered allelic variants for GST Z1 and GST A2 genes via EST database analysis.
• Assessed the substrate activity of a specific GST Z1 variant (GST Z1A) with dichloroacetic acid.

Implications:

• The identified Zeta class GSTs play a key role in tyrosine catabolism.
• A specific GST Z1 variant (GST Z1A) exhibits enhanced activity with dichloroacetic acid, suggesting therapeutic potential.
• EST database searching is a valuable method for discovering pharmacogenetically relevant gene families and variants.