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Literature summary extracted from

  • Li, D.; Fournel-Gigleux, S.; Barre, L.; Mulliert, G.; Netter, P.; Magdalou, J.; Ouzzine, M.
    Identification of aspartic acid and histidine residues mediating the reaction mechanism and the substrate specificity of the human UDP-glucuronosyltransferases 1A (2007), J. Biol. Chem., 282, 36514-36524.
    View publication on PubMed

Cloned(Commentary)

EC Number Cloned (Comment) Organism
2.4.1.17 expression of wild-type and mutant isozymes in Pichia pastoris Homo sapiens

Protein Variants

EC Number Protein Variants Comment Organism
2.4.1.17 D145A site-directed mutagenesis, mutation of isozyme UGT1A6 leading to reduced glucuronidation activity and altered kinetics compared to the wild-type enzyme Homo sapiens
2.4.1.17 D150A site-directed mutagenesis, mutation of isozyme UGT1A6, inactive mutant Homo sapiens
2.4.1.17 D357A site-directed mutagenesis, mutation of isozyme UGT1A6 leading to reduced glucuronidation activity and altered kinetics compared to the wild-type enzyme Homo sapiens
2.4.1.17 D394A site-directed mutagenesis, mutation of isozyme UGT1A6 leading to slightly reduced glucuronidation activity and altered kinetics compared to the wild-type enzyme Homo sapiens
2.4.1.17 D397A site-directed mutagenesis, mutation of isozyme UGT1A6 leading to reduced glucuronidation activity and altered kinetics compared to the wild-type enzyme Homo sapiens
2.4.1.17 D420A site-directed mutagenesis, mutation of isozyme UGT1A6 leading to reduced glucuronidation activity and altered kinetics compared to the wild-type enzyme Homo sapiens
2.4.1.17 D447A site-directed mutagenesis, mutation of isozyme UGT1A6 leading to highly reduced glucuronidation activity and altered kinetics compared to the wild-type enzyme Homo sapiens
2.4.1.17 D454A site-directed mutagenesis, mutation of isozyme UGT1A6 leading to reduced glucuronidation activity and altered kinetics compared to the wild-type enzyme Homo sapiens
2.4.1.17 D488A site-directed mutagenesis, mutation of isozyme UGT1A6, inactive mutant Homo sapiens
2.4.1.17 E287A site-directed mutagenesis, mutation of isozyme UGT1A6 leading to 1.4fold reduced glucuronidation activity compared to the wild-type enzyme Homo sapiens
2.4.1.17 E289A site-directed mutagenesis, mutation of isozyme UGT1A6 leading to 3.2fold reduced glucuronidation activity compared to the wild-type enzyme Homo sapiens
2.4.1.17 E297A site-directed mutagenesis, mutation of isozyme UGT1A6 leading to 2.0fold reduced glucuronidation activity compared to the wild-type enzyme Homo sapiens
2.4.1.17 E314A site-directed mutagenesis, mutation of isozyme UGT1A6 leading to 7.0fold reduced glucuronidation activity compared to the wild-type enzyme Homo sapiens
2.4.1.17 E378A site-directed mutagenesis, mutation of isozyme UGT1A6 leading to 150fold reduced glucuronidation activity compared to the wild-type enzyme Homo sapiens
2.4.1.17 E378D site-directed mutagenesis, mutation of isozyme UGT1A6 leading to reduced glucuronidation activity and altered kinetics compared to the wild-type enzyme Homo sapiens
2.4.1.17 E378S site-directed mutagenesis, mutation of isozyme UGT1A6 leading to reduced glucuronidation activity and altered kinetics compared to the wild-type enzyme Homo sapiens
2.4.1.17 E461A site-directed mutagenesis, mutation of isozyme UGT1A6 leading to 350fold reduced glucuronidation activity compared to the wild-type enzyme Homo sapiens
2.4.1.17 E461D site-directed mutagenesis, mutation of isozyme UGT1A6 leading to reduced glucuronidation activity and altered kinetics compared to the wild-type enzyme Homo sapiens
2.4.1.17 E461Q site-directed mutagenesis, mutation of isozyme UGT1A6 leading to reduced glucuronidation activity and altered kinetics compared to the wild-type enzyme Homo sapiens
2.4.1.17 E461S site-directed mutagenesis, mutation of isozyme UGT1A6 leading to reduced glucuronidation activity and altered kinetics compared to the wild-type enzyme Homo sapiens
2.4.1.17 H39P site-directed mutagenesis, mutation of His39 residue of isozyme UGT1A1 to proline leads to loss of glucuronidation of phenols but not of estrogens Homo sapiens
2.4.1.17 H40P site-directed mutagenesis, replacing of His40 residue of isozyme UGT1A3 with proline shifts the substrate specificity toward that of isozyme UGT1A4 with loss of glucuronidation of phenolic substrates Homo sapiens
2.4.1.17 P40H site-directed mutagenesis, replacing Pro-40 of isozyme UGT1A4 by histidine expands the glucuronidation activity of the enzyme to phenolic and carboxylic compounds, therefore, leading to UGT1A3-type isoform in terms of substrate specificity Homo sapiens

KM Value [mM]

EC Number KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
2.4.1.17 additional information
-
 additional information kinetics of wild-type UGT1A6 and mutants, overview Homo sapiens
2.4.1.17 0.00012
-
 4-Methylumbelliferone pH 7.4, 37°C, recombinant wild-type isozyme UGT1A6 Homo sapiens
2.4.1.17 0.00025
-
 UDP-D-glucuronate pH 7.4, 37°C, recombinant wild-type isozyme UGT1A6 Homo sapiens

Metals/Ions

EC Number Metals/Ions Comment Organism Structure
2.4.1.17 Mg2+
-
 Homo sapiens

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
2.4.1.17 UDP-D-glucuronate + acceptor Homo sapiens
-
 UDP + acceptor beta-D-glucuronoside
-
 ?

Organism

EC Number Organism UniProt Comment Textmining
2.4.1.17 Homo sapiens P19224 isozyme UGT1A6; diverse isozymes
-
2.4.1.17 Homo sapiens P22309 isozyme UGT1A1; isozyme UGT1A1
-
2.4.1.17 Homo sapiens P22310 isozyme UGT1A4; diverse isozymes
-
2.4.1.17 Homo sapiens P35503 isozyme UGT1A3; isozyme UGT1A3
-

Reaction

EC Number Reaction Comment Organism Reaction ID
2.4.1.17 UDP-alpha-D-glucuronate + acceptor = UDP + acceptor beta-D-glucuronoside aspartic acid residues, especially Asp150 and Asp488, and histidine residues mediate the acid-base reaction mechanism and the substrate specificity of the human subfamily of UDP-D-glucuronosyltransferases 1A catalyzing the nucleophilic attack of phenolic xenobiotics on UDP-D-glucuronic acid, leading to the formation of water-soluble glucuronides, overview Homo sapiens
a

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
2.4.1.17 additional information UGT1A1 substrate specificity, overview Homo sapiens ?
-
 ?
2.4.1.17 UDP-D-glucuronate + 1-naphthol isozyme UGT1A1 Homo sapiens UDP + 1-naphthyl beta-D-glucuronoside
-
 ?
2.4.1.17 UDP-D-glucuronate + 2-hydroxyestradiol isozyme UGT1A1 Homo sapiens UDP + 2-hydroxyestradiol beta-D-glucuronoside
-
 ?
2.4.1.17 UDP-D-glucuronate + 2-hydroxyestrone isozyme UGT1A1 Homo sapiens UDP + 2-hydroxyestrone beta-D-glucuronoside
-
 ?
2.4.1.17 UDP-D-glucuronate + 4-methylumbelliferone isozyme UGT1A1 Homo sapiens UDP + 4-methylumbelliferone beta-D-glucuronoside
-
 ?
2.4.1.17 UDP-D-glucuronate + 4-methylumbelliferone isozyme UGT1A6 Homo sapiens UDP + 4-methylumbelliferone beta-D-glucuronoside
-
 ?
2.4.1.17 UDP-D-glucuronate + 4-nitrophenol isozyme UGT1A1 Homo sapiens UDP + 4-nitrophenyl beta-D-glucuronoside
-
 ?
2.4.1.17 UDP-D-glucuronate + acceptor
-
 Homo sapiens UDP + acceptor beta-D-glucuronoside
-
 ?
2.4.1.17 UDP-D-glucuronate + beta-D-estradiol isozyme UGT1A1 Homo sapiens UDP + beta-estradiol 3-O-beta-D-glucuronoside
-
 ?
2.4.1.17 UDP-D-glucuronate + eugenol isozyme UGT1A1 Homo sapiens UDP + eugenol beta-D-glucuronoside
-
 ?
2.4.1.17 UDP-D-glucuronate + octylgallate isozyme UGT1A1 Homo sapiens UDP + octylgallate beta-D-glucuronoside
-
 ?
2.4.1.17 UDP-D-glucuronate + scopoletin isozyme UGT1A1 Homo sapiens UDP + scopoletin beta-D-glucuronoside
-
 ?

Synonyms

EC Number Synonyms Comment Organism
2.4.1.17 UDP-glucuronosyltransferase
-
 Homo sapiens
2.4.1.17 UDP-glucuronosyltransferase 1A1
-
 Homo sapiens
2.4.1.17 UGT
-
 Homo sapiens

Temperature Optimum [°C]

EC Number Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
2.4.1.17 37
-
 assay at Homo sapiens

pH Optimum

EC Number pH Optimum Minimum pH Optimum Maximum Comment Organism
2.4.1.17 7.4
-
 assay at Homo sapiens