title: Understanding substrate selectivity of human UDP-glucuronosyltransferases through QSAR modeling and analysis of homologous enzymes.
abstract: The UDP-glucuronosyltransferase (UGT) enzyme catalyzes the glucuronidation reaction which is a major metabolic and detoxification pathway in humans. Understanding the mechanisms for substrate recognition by UGT assumes great importance in an attempt to predict its contribution to xenobiotic/drug disposition in vivo.        Spurred on by this interest, 2D/3D-quantitative structure activity relationships and pharmacophore models have been established in the absence of a complete mammalian UGT crystal structure.        This review discusses the recent progress in modeling human UGT substrates including those with multiple sites of glucuronidation. A better understanding of UGT active site contributing to substrate selectivity (and regioselectivity) from the homologous enzymes (i.e. plant and bacterial UGTs, all belong to family 1 of glycosyltransferase (GT1)) is also highlighted, as these enzymes share a common catalytic mechanism and/or overlapping substrate selectivity.
authors.affiliation: Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX 77030, USA.
authors.forename: Dong
authors.initials: D
authors.lastname: Dong
authors.forename: Roland
authors.initials: R
authors.lastname: Ako
authors.forename: Ming
authors.initials: M
authors.lastname: Hu
authors.forename: Baojian
authors.initials: B
authors.lastname: Wu
mesh_terms: D000595:Amino Acid Sequence; D055162:Biocatalysis; D014453:Glucuronosyltransferase / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D021281:Quantitative Structure-Activity Relationship; D040681:Structural Homology, Protein; D013379:Substrate Specificity
chemical_list: D014453:Glucuronosyltransferase