Premium
Substrate specificity of the human UDP‐glucuronosyltransferase UGT2B4 and UGT2B7
Author(s) -
Barre Lydia,
FournelGigleux Sylvie,
Finel Moshe,
Netter Patrick,
Magdalou Jacques,
Ouzzine Mohamed
Publication year - 2007
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2007.05670.x
Subject(s) - ugt2b7 , chemistry , glucuronidation , tyrosine , phenylalanine , leucine , biochemistry , valine , amino acid , enzyme , microsome
The human UDP‐glucuronosyltransferase (UGT) isoforms UGT2B4 and UGT2B7 play a major role in the detoxification of bile acids, steroids and phenols. These two isoforms present distinct but overlapping substrate specificity, sharing common substrates such as the bile acid hyodeoxycholic acid (HDCA) and catechol‐estrogens. Here, we show that in UGT2B4, substitution of phenylalanine 33 by leucine suppressed the activity towards HDCA, and impaired the glucuronidation of several substrates, including 4‐hydroxyestrone and 17‐epiestriol. On the other hand, the substrate specificity of the mutant UGT2B4F33Y, in which phenylalanine was replaced by tyrosine, as found at position 33 of UGT2B7, was similar to wild‐type UGT2B4. In the case of UGT2B7, replacement of tyrosine 33 by leucine strongly reduced the activity towards all the tested substrates, with the exception of 17‐epiestriol. In contrast, mutation of tyrosine 33 by phenylalanine exhibited similar or even somewhat higher activities than wild‐type UGT2B7. Hence, the results strongly indicated that the presence of an aromatic residue at position 33 is important for the activity and substrate specificity of both UGT2B4 and UGT2B7.