A distinct human testis and brain mu-class glutathione S-transferase. Molecular cloning and characterization of a form present even in individuals lacking hepatic type mu isoenzymes.
mu-Class glutathione S-transferases (GSTs) were identified in all 13 human testes and 28 brains examined; even subjects whose livers were devoid of mu-GSTs expressed extrahepatic GSTs of this class. Testes and brains from individuals with mu-class GSTs in their livers had additional forms that also reflected the liver phenotypes. An isoenzyme with an isoelectric point of 5.2, which was a major GST in testis and present as well in cerebral cortex but not detected in any livers, was identified and purified. Sequence analysis of peptides derived by cleavage of the testicular mu-class GST by Achromobacter protease I revealed distinct aspects of primary structure not found previously in any mammalian mu-class GSTs. These unique features included a blocked and extended amino terminus and 3 additional residues (Pro-Val-Cys) at the carboxyl terminus. This structure was confirmed by molecular cloning and sequencing of cDNAs derived from human testis and brain libraries. In the coding region the mRNA of the brain-testis mu-class GST was 75% homologous with that of the liver form, and its 3'-untranslated sequence was mostly divergent, indicating that it is the product of a separate gene. Distinct catalytic and structural properties of the testis-brain mu-class GSTs suggest that these GSTs may be uniquely involved in blood-barrier functions common to both organs.
Campbell
E
E
Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York 10461.
Takahashi
Y
Y
Abramovitz
M
M
Peretz
M
M
Listowsky
I
I
D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D001483:Base Sequence; D001921:Brain / Q000201:enzymology*; D002648:Child; D002675:Child, Preschool; D003001:Cloning, Molecular; D005982:Glutathione Transferase / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007223:Infant; D007526:Isoelectric Point; D007527:Isoenzymes / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009693:Nucleic Acid Hybridization; D010449:Peptide Mapping; D012333:RNA, Messenger / Q000235:genetics; D012689:Sequence Homology, Nucleic Acid; D013737:Testis / Q000201:enzymology*
D007527:Isoenzymes; D012333:RNA, Messenger; D005982:Glutathione Transferase