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Literature summary for 2.4.1.17 extracted from

  • Fujiwara, R.; Nakajima, M.; Yamanaka, H.; Yokoi, T.
    Key amino acid residues responsible for the differences in substrate specificity of human UDP-glucuronosyltransferase (UGT) 1A9 and UGT1A8 (2009), Drug Metab. Dispos., 37, 41-46.
    View publication on PubMed

Cloned(Commentary)

Cloned (Comment) Organism
expression in HEK-293 cell Homo sapiens
expression in insect cell Homo sapiens
expression of wild-type isozyme UGT1A10 in insect cells, overview Homo sapiens
expression of wild-type isozyme UGT1A7 in insect cells, overview Homo sapiens
expression of wild-type isozyme UGT1A8 in insect cells, overview Homo sapiens
expression of wild-type isozyme UGT1A9 and mutants in HEK-293 cells, expression of wild-type isozyme UGT1A9 in insect cells, expression levels, overview Homo sapiens

Protein Variants

Protein Variants Comment Organism
D152A site-directed mutagenesis, exchange of a conserved residue from isozyme UGT1A9 for the corresponding residue in isozyme UGT1A8, the mutant shows altered substrate specificity compared to wild-type isozyme UGT1A9, the mutant is active with the substrate 3-hydroxydesloratadine specific for isozyme UGT1A8 Homo sapiens
E241A site-directed mutagenesis, exchange of a conserved residue from isozyme UGT1A9 for the corresponding residue in isozyme UGT1A8, the mutant shows altered substrate specificity compared to wild-type isozyme UGT1A9 Homo sapiens
E241A replacement of amino acid to corresponding residue of isoform UGT1A8 Homo sapiens
K91M/A92D site-directed mutagenesis, exchange of conserved residues from isozyme UGT1A9 for the corresponding residues in isozyme UGT1A8, the mutant shows altered substrate specificity compared to wild-type isozyme UGT1A9 Homo sapiens
K91M/A92D replacement of amino acid to corresponding residue of isoform UGT1A8 Homo sapiens
L173A site-directed mutagenesis, exchange of a conserved residue from isozyme UGT1A9 for the corresponding residue in isozyme UGT1A8, the mutant shows altered substrate specificity compared to wild-type isozyme UGT1A9 Homo sapiens
L173A replacement of amino acid to corresponding residue of isoform UGT1A8 Homo sapiens
L219F/H221Q/R222Y site-directed mutagenesis, exchange of conserved residues from isozyme UGT1A9 for the corresponding residues in isozyme UGT1A8, the mutant shows altered substrate specificity compared to wild-type isozyme UGT1A9 Homo sapiens
L219F/H221Q/R222Y replacement of amino acid to corresponding residue of isoform UGT1A8 Homo sapiens
N152A replacement of amino acid to corresponding residue of isoform UGT1A8, increase in Km and Vmax values for substrates 4-methylumbelliferone and 4-nitrophenol. Active against substrate 3-hydroxydesloratadine, specifc substrate of isoform UGT1A8 Homo sapiens
R42Q site-directed mutagenesis, exchange of a conserved residue from isozyme UGT1A9 for the corresponding residue in isozyme UGT1A8, the mutant shows altered substrate specificity compared to wild-type isozyme UGT1A9 Homo sapiens
R42Q replacement of amino acid to corresponding residue of isoform UGT1A8, increase in Km value for substrates 4-methylumbelliferone and 4-nitrophenol Homo sapiens
Y106F/G111S/D115G site-directed mutagenesis, exchange of conserved residues from isozyme UGT1A9 for the corresponding residues in isozyme UGT1A8, the mutant shows altered substrate specificity compared to wild-type isozyme UGT1A9 Homo sapiens
Y106F/G111S/D115G replacement of amino acid to corresponding residue of isoform UGT1A8, increase in Vmax value for substrates 4-methylumbelliferone and 4-nitrophenol Homo sapiens

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
additional information
-
additional information kinetic analysis of wild-type isozyme UGT1A9 and mutants expressed in HEK293 cells, overview Homo sapiens
0.0021
-
4-Methylumbelliferone mutant L173A, pH 7.4, 37°C Homo sapiens
0.0036
-
4-Methylumbelliferone mutant K91M/A92D, pH 7.4, 37°C Homo sapiens
0.0044
-
4-Methylumbelliferone wild-type, pH 7.4, 37°C Homo sapiens
0.0044
-
4-Methylumbelliferone mutant E241A, pH 7.4, 37°C Homo sapiens
0.0056
-
4-Methylumbelliferone mutant Y106F/G111S/D115G, pH 7.4, 37°C Homo sapiens
0.0059
-
4-Methylumbelliferone mutant L219F/H221Q/R222Y, pH 7.4, 37°C Homo sapiens
0.0091
-
4-Methylumbelliferone mutant N152A, pH 7.4, 37°C Homo sapiens
0.0101
-
4-Methylumbelliferone mutant R42Q, pH 7.4, 37°C Homo sapiens
0.0102
-
4-nitrophenol mutant Y106F/G111S/D115G, pH 7.4, 37°C Homo sapiens
0.0152
-
4-nitrophenol mutant L219F/H221Q/R222Y, pH 7.4, 37°C Homo sapiens
0.0157
-
4-nitrophenol mutant L173A, pH 7.4, 37°C Homo sapiens
0.0169
-
4-nitrophenol wild-type, pH 7.4, 37°C Homo sapiens
0.0178
-
4-nitrophenol mutant K91M/A92D, pH 7.4, 37°C Homo sapiens
0.0188
-
4-nitrophenol mutant E241A, pH 7.4, 37°C Homo sapiens
0.03
-
4-nitrophenol mutant R42Q, pH 7.4, 37°C Homo sapiens
0.0492
-
4-nitrophenol mutant N152A, pH 7.4, 37°C Homo sapiens
0.1917
-
4-Methylumbelliferone isoform UGT1A8, pH 7.4, 37°C 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 + 3-hydroxydesloratadine Homo sapiens specific substrate of isozyme UGT1A8 UDP + 3-hydroxydesloratadine beta-O-D-glucuronoside
-
?
UDP-D-glucuronate + acceptor Homo sapiens the enzyme plays a key role in the metabolism of endogenous and exogenous compounds UDP + acceptor beta-D-glucuronoside
-
?

Organism

Organism UniProt Comment Textmining
Homo sapiens
-
isoform UGT1A8
-
Homo sapiens
-
isoform UGT1A9
-
Homo sapiens O60656 isozyme UGT1A9; isozyme UGT1A9
-
Homo sapiens Q9HAW7 isozyme UGT1A7; isozyme UGT1A7
-
Homo sapiens Q9HAW8 isozyme UGT1A10; isozyme UGT1A10
-
Homo sapiens Q9HAW9 isozyme UGT1A8; isozyme UGT1A8
-

Source Tissue

Source Tissue Comment Organism Textmining
liver
-
Homo sapiens
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
3-hydroxydesloratadine + UDP-glucuronate specific substrate of isoform UGT1A8 Homo sapiens UDP + 3-hydroxydesloratadinyl-O-glucuronide
-
?
3-hydroxydesloratadine + UDP-glucuronate specific substrate of isoform UGT1A8, substrate of isoform UGT1A9 mutant N152A Homo sapiens UDP + 3-hydroxydesloratadinyl-O-glucuronide
-
?
4-methylumbelliferone + UDP-glucuronate
-
Homo sapiens UDP + 4-methylumbelliferyl-7-O-beta-D-glucuronide
-
?
4-nitrophenol + UDP-glucuronate
-
Homo sapiens 4-nitrophenyl beta-D-glucuronide + UDP
-
?
additional information key amino acid residues responsible for the differences in substrate specificity of isozymes UGT1A9 and UGT1A8, overview Homo sapiens ?
-
?
additional information no substrate of isoform UGT1A8: 4-nitrophenol Homo sapiens ?
-
?
UDP-D-glucuronate + 3-hydroxydesloratadine specific substrate of isozyme UGT1A8 Homo sapiens UDP + 3-hydroxydesloratadine beta-O-D-glucuronoside
-
?
UDP-D-glucuronate + 4-methylumbelliferone
-
Homo sapiens UDP + 4-methylumbelliferyl beta-O-glucuronoside
-
?
UDP-D-glucuronate + 4-nitrophenol
-
Homo sapiens UDP + 4-nitrophenyl beta-O-D-glucuronoside
-
?
UDP-D-glucuronate + acceptor the enzyme plays a key role in the metabolism of endogenous and exogenous compounds Homo sapiens UDP + acceptor beta-D-glucuronoside
-
?

Subunits

Subunits Comment Organism
dimer
-
Homo sapiens

Synonyms

Synonyms Comment Organism
UDP-glucuronosyltransferase
-
Homo sapiens
UGT1A8
-
Homo sapiens
UGT1A9
-
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