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Literature summary for 2.4.1.17 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)

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

Protein Variants

Protein Variants Comment Organism
D145A site-directed mutagenesis, mutation of isozyme UGT1A6 leading to reduced glucuronidation activity and altered kinetics compared to the wild-type enzyme Homo sapiens
D150A site-directed mutagenesis, mutation of isozyme UGT1A6, inactive mutant Homo sapiens
D357A site-directed mutagenesis, mutation of isozyme UGT1A6 leading to reduced glucuronidation activity and altered kinetics compared to the wild-type enzyme Homo sapiens
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
D397A site-directed mutagenesis, mutation of isozyme UGT1A6 leading to reduced glucuronidation activity and altered kinetics compared to the wild-type enzyme Homo sapiens
D420A site-directed mutagenesis, mutation of isozyme UGT1A6 leading to reduced glucuronidation activity and altered kinetics compared to the wild-type enzyme Homo sapiens
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
D454A site-directed mutagenesis, mutation of isozyme UGT1A6 leading to reduced glucuronidation activity and altered kinetics compared to the wild-type enzyme Homo sapiens
D488A site-directed mutagenesis, mutation of isozyme UGT1A6, inactive mutant Homo sapiens
E287A site-directed mutagenesis, mutation of isozyme UGT1A6 leading to 1.4fold reduced glucuronidation activity compared to the wild-type enzyme Homo sapiens
E289A site-directed mutagenesis, mutation of isozyme UGT1A6 leading to 3.2fold reduced glucuronidation activity compared to the wild-type enzyme Homo sapiens
E297A site-directed mutagenesis, mutation of isozyme UGT1A6 leading to 2.0fold reduced glucuronidation activity compared to the wild-type enzyme Homo sapiens
E314A site-directed mutagenesis, mutation of isozyme UGT1A6 leading to 7.0fold reduced glucuronidation activity compared to the wild-type enzyme Homo sapiens
E378A site-directed mutagenesis, mutation of isozyme UGT1A6 leading to 150fold reduced glucuronidation activity compared to the wild-type enzyme Homo sapiens
E378D site-directed mutagenesis, mutation of isozyme UGT1A6 leading to reduced glucuronidation activity and altered kinetics compared to the wild-type enzyme Homo sapiens
E378S site-directed mutagenesis, mutation of isozyme UGT1A6 leading to reduced glucuronidation activity and altered kinetics compared to the wild-type enzyme Homo sapiens
E461A site-directed mutagenesis, mutation of isozyme UGT1A6 leading to 350fold reduced glucuronidation activity compared to the wild-type enzyme Homo sapiens
E461D site-directed mutagenesis, mutation of isozyme UGT1A6 leading to reduced glucuronidation activity and altered kinetics compared to the wild-type enzyme Homo sapiens
E461Q site-directed mutagenesis, mutation of isozyme UGT1A6 leading to reduced glucuronidation activity and altered kinetics compared to the wild-type enzyme Homo sapiens
E461S site-directed mutagenesis, mutation of isozyme UGT1A6 leading to reduced glucuronidation activity and altered kinetics compared to the wild-type enzyme Homo sapiens
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
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
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]

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

Metals/Ions

Metals/Ions Comment Organism Structure
Mg2+
-
Homo sapiens

Natural Substrates/ Products (Substrates)

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

Organism

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

Reaction

Reaction Comment Organism Reaction ID
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

Substrates and Products (Substrate)

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

Synonyms

Synonyms Comment Organism
UDP-glucuronosyltransferase
-
Homo sapiens
UDP-glucuronosyltransferase 1A1
-
Homo sapiens
UGT
-
Homo sapiens

Temperature Optimum [°C]

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

pH Optimum

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