Critical roles of residues 36 and 40 in the phenol and tertiary amine aglycone substrate selectivities of UDP-glucuronosyltransferases 1A3 and 1A4

T Kubota, BC Lewis, DJ Elliot, PI Mackenzie…

Index: Kubota, Takahiro; Lewis, Benjamin C.; Elliot, David J.; Mackenzie, Peter I.; Miners, John O. Molecular Pharmacology, 2007 , vol. 72, # 4 p. 1054 - 1062

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Citation Number: 45

Abstract

Abstract Despite high sequence identity, UGT1A3 and UGT1A4 differ in terms of substrate selectivity. UGT1A3 glucuronidates the planar phenols 1-naphthol (1-NP) and 4- methylumbelliferone (4-MU), whereas UGT1A4 converts the tertiary amines lamotrigine (LTG) and trifluoperazine (TFP) to quaternary ammonium glucuronides. Residues 45 to 154 (which incorporate 21 of the 35 amino acid differences) and 45 to 535 were exchanged ...