Related Experiment Video
Updated: Jun 13, 2026

Modification and Functionalization of the Guanidine Group by Tailor-made Precursors
Published on: April 27, 2017
Ligand orientation governs conjugation capacity of UDP-glucuronosyltransferase 1A1
Yutaka Takaoka1, Mika Ohta, Atsuko Takeuchi
1Division of Applied Genome Science and Bioinformatics, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan. ytakaoka@med.kobe-u.ac.jp
Abstract:
UDP-glucuronosyltransferase 1A1 (UGT1A1) is an endoplasmic reticulum membrane protein that catalyses glucuronidation. Mutant UGT1A1 possesses a different conjugation capacity, and the molecular mechanisms regulating these conjugation reactions are as yet unclear. To elucidate these molecular mechanisms, we simulated and analysed the glucuronidation of wild-type UGT1A1 and six UGT1A1 mutants, with bilirubin as the substrate. We found that only the orientation of the substrates correlated with the conjugation capacity in in vitro experiments. Inasmuch as glucuronidation is an intermolecular rearrangement reaction, we find that the conjugation reaction proceeds only when the hydroxyl group of the substrate is oriented towards the coenzyme, which allows the proton transfer to occur.
More Related Videos
Related Concept Videos
Phase II Reactions: Glucuronidation
Ligand Binding Sites
Protein-ligand interactions are quite specific; even though numerous potential ligands surround a cellular protein at any given time, only a particular ligand can bind to that protein. Moreover, a ligand binds only to a dedicated area on the surface of the protein, known as the...
Ligand Binding Sites
Protein-ligand interactions are quite specific; even though numerous potential ligands surround a cellular protein at any given time, only a particular ligand can bind to that protein. Moreover, a ligand binds only to a dedicated area on the surface of the protein, known as the...
Ligand Binding and Linkage
Ligand Binding and Linkage
Drug Metabolism: Phase II Reactions

