RT Journal Article
SR Electronic
T1 Identification of Novel Glutathione Transferases and Polymorphic Variants by Expressed Sequence Tag Database Analysis
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 544
OP 547
VO 29
IS 4
A1 P. G. Board
A1 G. Chelvanayagam
A1 L. S. Jermiin
A1 N. Tetlow
A1 H.-F. Tzeng
A1 M. W. Anders
A1 A. C. Blackburn
YR 2001
UL http://dmd.aspetjournals.org/content/29/4/544.abstract
AB The human expressed sequence tag (EST) database can be searched by different sequence alignment strategies to identify new members of gene families and allelic variants. To illustrate the value of database analysis for gene discovery, we have focused on the glutathioneS-transferase (GST) super family, an approach that has led to the identification of the Zeta class. The Zeta class GSTs catalyze the glutathione-dependent biotransformation of α-haloacids and the isomerization of maleylacetoacetic acid to fumarylacetoacetic acid, an essential step in the catabolism of tyrosine. Allelic variants of the GST Z1 and GST A2 genes have also been identified by EST database analysis. One GST Z1 variant (GST Z1A) has significantly higher activity with dichloroacetic acid as a substrate than other GST Z1 isoforms. This variant may be important in the clinical treatment of lactic acidosis where dichloroacetic acid is prescribed. Our experience with the application of EST database searching methods suggests that it may be productively applied to other gene families of pharmacogenetic interest. The American Society for Pharmacology and Experimental Therapeutics