Characterization of the human Omega class glutathione transferase genes and associated polymorphisms.

Astrid K Whitbread, Natasha Tetlow, Helen J Eyre, Grant R Sutherland, Philip G Board

Molecular Genetics Group, John Curtin School of Medical Research, Australian National University, Canberra, Australia.

Pharmacogenetics 2003 Mar

filter terms:

The Omega class glutathione transferases (GSTs) have been identified in many organisms, including human, mouse, rat, pig, Caenorhabditis eglands and Drosophila melanogaster. These GSTs have poor activity with common GST substrates, but exhibit novel glutathione-dependent thioltransferase, dehydroascorbate reductase and monomethylarsonate reductase activities, and modulate Ca release by ryanodine receptors. An investigation of the genomic organization of human GSTO1 identified a second actively transcribed member of the Omega class (GSTO1). Both GSTO1 and GSTO2 are composed of six exons and are separated by 7.5 kb on chromosome 10q24.3. A third sequence that appears to be a reverse-transcribed pseudogene (GSTO3p) has been identified on chromosome 3. GSTO2 has 64% amino acid identity with GSTO1 and conserves the cysteine residue at position 32, which is thought to be important in the active site of GSTO1. Expression of GSTO2 mRNA was seen in a range of tissues, including the liver, kidney, skeletal muscle and prostate. The strongest GSTO2 expression was in the testis, which also expresses a larger transcript than other tissues. Characterization of recombinant GSTO2 has been limited by its poor solubility. Two functional polymorphisms of GSTO1 have been identified. One alters a splice junction and causes the deletion of E155 and another results in an A140D substitution. Characterization of these variants revealed that the A140D substitution affects neither heat stability, nor activity towards 1-chloro-2,4-dinitrobenzene or hydroxyethyl disulphide. In contrast, deletion of residue E155 appears to contribute towards both a loss of heat stability and increased enzymatic activity. Copyright 2003 Lippincott Williams & Wilkins

Citation

Astrid K Whitbread, Natasha Tetlow, Helen J Eyre, Grant R Sutherland, Philip G Board. Characterization of the human Omega class glutathione transferase genes and associated polymorphisms. Pharmacogenetics. 2003 Mar;13(3):131-44