Publication — IRIC

1H, 13C and 15N chemical shift assignments of the C-terminal domain of human UDP-Glucuronosyltransferase 2B7 (UGT2B7-C).

The human UDP-glucuronosyltransferase (UGT) family of enzymes catalyze the covalent addition of glucuronic acid to a wide range of compounds, generally rendering them inactive. Although important for clearance of environmental toxins and metabolites, UGT activation can lead to inappropriate glucuronidation of therapeutics underlying drug resistance. Indeed, 50% of medications are glucuronidated. To better understand this mode of resistance, we studied the UGT2B7 enzyme associated with glucuronidation of cancer drugs such as Tamoxifen and Sorafenib. We report 1H, 13C and 15N backbone (> 90%) and side-chain assignments (~ 78% completeness according to CYANA) for the C-terminal domain of UGT2B7 (UGT2B7-C). Given the biomedical importance of this family of enzymes, our assignments will provide a key tool for improving understanding of the biochemical basis for substrate selectivity and other aspects of enzyme activity. This in turn will inform on drug design to overcome UGT-related drug resistance.

Date de publication
1er octobre 2021
Chercheurs
Osborne MJ, Rahardjo AK, Volpon L, Borden K
Référence PubMed
Biomol NMR Assign 2021;15(2):323-328
ID PubMed
33870481
Affiliation
Department of Pathology and Cell Biology, Institute of Research in Immunology and Cancer (IRIC), Université de Montréal, Pavillion Marcelle-Coutu, Chemin Polytechnique, Montreal, QC, Canada.