Abstract
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.
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Data availability
The assignments have been deposited to the BMRB under the accession code 50789.
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Acknowledgements
This work was supported by NIH 98571, NIH 80728, LLS TRP, CIHR, and IRICoR. KLBB holds a Canada Research Chair in Molecular Biology of the Cell Nucleus.
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Osborne, M.J., Rahardjo, A.K., Volpon, L. et al. 1H, 13C and 15N chemical shift assignments of the C-terminal domain of human UDP-Glucuronosyltransferase 2B7 (UGT2B7-C). Biomol NMR Assign 15, 323–328 (2021). https://doi.org/10.1007/s12104-021-10024-9
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DOI: https://doi.org/10.1007/s12104-021-10024-9