Information on EC 1.14.11.11 - hyoscyamine (6S)-dioxygenase

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The enzyme appears in viruses and cellular organisms

EC NUMBER
COMMENTARY hide
1.14.11.11
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RECOMMENDED NAME
GeneOntology No.
hyoscyamine (6S)-dioxygenase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
L-hyoscyamine + 2-oxoglutarate + O2 = (6S)-hydroxyhyoscyamine + succinate + CO2
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
decarboxylation
-
-
-
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epoxidation
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-
-
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hydroxylation
oxidation
-
-
-
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redox reaction
-
-
-
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reduction
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-
-
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PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
hyoscyamine and scopolamine biosynthesis
-
-
superpathway of hyoscyamine and scopolamine biosynthesis
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-
Tropane, piperidine and pyridine alkaloid biosynthesis
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Metabolic pathways
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Biosynthesis of secondary metabolites
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SYSTEMATIC NAME
IUBMB Comments
L-hyoscyamine,2-oxoglutarate:oxygen oxidoreductase ((6S)-hydroxylating)
Requires Fe2+ and ascorbate.
CAS REGISTRY NUMBER
COMMENTARY hide
103865-33-4
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ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
SwissProt
Manually annotated by BRENDA team
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UniProt
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
Hyoscyamus gyorffi
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-
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Manually annotated by BRENDA team
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-
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Manually annotated by BRENDA team
gene h6h
UniProt
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
evolution
metabolism
additional information
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
(6S)-6-hydroxyhyoscyamine + 2-oxoglutarate + O2
scopolamine + succinate + CO2
show the reaction diagram
2-hydroxy-3-phenylpropionyltropine + 2-oxoglutarate + O2
2-hydroxy-3-phenylpropionyl-6-hydroxytropine + succinate + CO2
show the reaction diagram
-
15% of the activity with L-hyoscyamine
-
?
2-oxoglutarate + p-hydroxyatropine + O2
?
show the reaction diagram
-
26% of the activity with L-hyoscyamine
-
-
?
2-oxoglutarate + trans-cinnamoyltropine + O2
succinate + trans-cinnamoyl-6-hydroxytropine + CO2
show the reaction diagram
-
39% of the activity with L-hyoscyamine
-
?
3-hydroxy-3-phenylpropionyltropine + 2-oxoglutarate + O2
3-hydroxy-3-phenylpropionyl-6-hydroxytropine + succinate + CO2
show the reaction diagram
-
56% of the activity with L-hyoscyamine
-
?
6,7-dehydrohyoscyamine + 2-oxoglutarate + O2
scopolamine + succinate + CO2
show the reaction diagram
-
119% of the activity with L-hyoscyamine
-
?
6beta-hydroxyhyoscyamine
scopolamine
show the reaction diagram
-
weak epoxidase activity, 2-5% of the hydroxylase activity
-
-
?
6beta-hydroxyhyoscyamine + ?
scopolamine + ?
show the reaction diagram
-
-
-
?
8-methyl-8-azabicyclo[3.2.1]octan-3-yl 2-(4-(dimethylamino)phenyl)acetate + 2-oxoglutarate + O2
?
show the reaction diagram
-
-
-
-
?
8-methyl-8-azabicyclo[3.2.1]octan-3-yl benzoate + 2-oxoglutarate + O2
?
show the reaction diagram
-
-
-
-
?
apoatropine + 2-oxoglutarate + O2
6-hydroxyapoatropine + succinate + CO2
show the reaction diagram
-
45% of the activity with L-hyoscyamine
-
?
hyoscyamine + O2 + 2-oxoglutarate + O2
scopolamine + succinate + CO2
show the reaction diagram
-
-
-
-
?
isobutyltropine + 2-oxoglutarate + O2
?
show the reaction diagram
-
15% of the activity with L-hyoscyamine
-
-
?
L-homatropine + 2-oxoglutarate + O2
6-hydroxyhomatropine + succinate + CO2
show the reaction diagram
-
81% of the activity with L-hyoscyamine
-
?
L-hyoscyamine + 2-oxoglutarate + O2
(6S)-hydroxyhyoscyamine + succinate + CO2
show the reaction diagram
L-hyoscyamine + 2-oxoglutarate + O2
6beta-hydroxyhyoscyamine + succinate + CO2
show the reaction diagram
L-norhyoscyamine + 2-oxoglutarate + O2
6-hydroxynorhyoscyamine + succinate + CO2
show the reaction diagram
-
81% of the activity with L-hyoscyamine
-
?
noratropine-N-acetic acid + 2-oxoglutarate + O2
?
show the reaction diagram
-
17% of the activity with L-hyoscyamine
-
-
?
phenylacetyltropine + 2-oxoglutarate + O2
6-hydroxyphenylacetyltropine + succinate + CO2
show the reaction diagram
-
81% of the activity with L-hyoscyamine
-
?
phenylalanyltropine + 2-oxoglutarate + O2
?
show the reaction diagram
-
8% of the activity with L-hyoscyamine
-
-
?
additional information
?
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
(6S)-6-hydroxyhyoscyamine + 2-oxoglutarate + O2
scopolamine + succinate + CO2
show the reaction diagram
L-hyoscyamine + 2-oxoglutarate + O2
(6S)-hydroxyhyoscyamine + succinate + CO2
show the reaction diagram
L-hyoscyamine + 2-oxoglutarate + O2
6beta-hydroxyhyoscyamine + succinate + CO2
show the reaction diagram
additional information
?
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(1R,2R,4S,5S,7s)-7-{[(2S)-3-hydroxy-2-phenylpropanoyl]oxy}-9,9-dimethyl-3-oxa-9-azoniatricyclo[3.3.1.02,4]nonane
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; slight inhibition by the substrate analogue
1,10-phenanthroline
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0.1 mM, 35% inhibition
1-methylpiperidin-4-yl 2-phenylacetate
-
-
2,2'-dipyridyl
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0.1 mM, 15% inhibition
3,4-dihydroxybenzoate
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-
3,4-dihydroxycinnamate
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3,4-dihydroxymandelate
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3,4-Dihydroxyphenylacetate
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3,4-Dihydroxyphenylpropionate
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3-oxoglutaric acid
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-
5,7-dehydrohyoscyamine
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6,7-Dehydrohyoscyamine
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8-methyl-8-azabicyclo[3.2.1]octan-3-yl 2-(4-(dimethylamino)phenyl)acetate
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8-methyl-8-azabicyclo[3.2.1]octan-3-yl 3-phenylpropanoate
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8-methyl-8-azabicyclo[3.2.1]octan-3-yl benzoate
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8-oxabicyclo[3.2.1]octan-3-yl 2-phenylacetate
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-
Apoatropine
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-
Bathocuproine
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0.1 mM, 27% inhibition
Cd2+
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0.4 mM, complete inhibition
Co2+
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0.4 mM, complete inhibition
diethyldithiocarbamate
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0.1 mM, 37% inhibition
fumarate
-
-
Hg2+
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0.4 mM, 96% inhibition
L-Homatropine
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-
Mg2+
5 mM, 14% inhibition
nitroblue tetrazolium
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-
Noratropine-N-acetic acid
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-
Phenylacetyltropine
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pyridine 2,3-dicarboxylate
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competitive with respect to 2-oxoglutarate
Pyridine 2,4-dicarboxylate
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competitive with respect to 2-oxoglutarate
Pyridine 3,4-dicarboxylate
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Tiron
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0.1 mM, 44% inhibition
additional information
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synthesis and inhibitory potencies of substrate analogues, overview. No inhibition by substrate analogues 1-methylpiperidin-4-yl 2-phenylacetate, 8-methyl-8-azabicyclo[3.2.1]octan-3-yl 3-phenylpropanoate, and 8-oxabicyclo[3.2.1]octan-3-yl 2-phenylacetate
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
5,7-dimethyl-5,6,7,8-tetrahydropterin
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partial activation
acetone
ascorbate
catalase
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dehydroascorbate
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partial activation
dithiothreitol
isoascorbate
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partial activation
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.043 - 0.057
2-oxoglutarate
0.01
6,7-Dehydrohyoscyamine
-
-
0.017
6beta-hydroxyhyosyamine
pH 7.4
0.0151
hyoscyamine
pH 7.4
0.017 - 0.0521
L-hyoscyamine
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.009
Pyridine 2,4-dicarboxylate
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-
0.09
Pyridine 3,4-dicarboxylate
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
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-
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.6
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recombinant enzyme
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
5 - 7.4
pH 5.0: 20% of maximal activity, pH 7.4: optimum
6 - 9
-
about 50% of maximal activity at pH 6.0 and pH 9.0
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
34
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recombinant enzyme
pI VALUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
5.08
sequence calculation
5.1
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calculated
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
additional information
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
41000
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gel filtration
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
monomer
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1 * 39238, recombinant enzyme, mass spectrometry, 1 * 39369, sequence calculation
ORGANIC SOLVENT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Acetone
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-20C, purified recombinant enzyme, 20 mM phosphate, 2 months, loss of approximately 20% of activity
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-20C, stable for more than 3 months
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4C, purified recombinant enzyme, 20 mM phosphate, 4 days, loss of over 50% activity
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Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
recombinant enzyme
recombinant His-tagged enzyme from Escherichia coli by nickel affinity chromatography
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recombinant N- or C-terminally His-tagged from Escherichia coli by nickel affinity chromatography
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recombinant N-terminally His- or GST-tagged enzyme from Escherichia coli strain BL21 (DE3) by nickel or glutathione affinity chromatography, respectively
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Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
cDNA from Hyoscyamus niger is simultaneously introduced into Nicotiana tabacum using particle bombardment and expressed under the control of the CaMV 35S promoter
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DmH6H gene, expression of the His-tagged enzyme in Escherichia coli
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DNA and amino acid sequence determination and analysis, overexpression of N- or C-terminally His-tagged enzyme in Escherichia coli strain BL21 (DE3), AbH6H loses of the first amino acid methionine during transcription
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DNA and amino acid sequence determination and analysis, overexpression of N-terminally His- or GST-tagged enzyme in Escherichia coli strain BL21 (DE3)
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expressed in Atropa baetica
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expressed in Duboisia leichhardtii
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expressed in Nicotiana tabacum and Hyoscyamus muticus
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expression in Escherichia coli
expression in Escherichia coli as a fusion protein to maltose-binding protein
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expression in Escherichia coli XL1B
expression in Saccharomyces cerevisiae in tagged and untagged form
gene h6h, DNA and amino acid sequence determination and analysis, sequence comparisons and phylogenetic tree, gene expression profiling and real-time RT-PCR analysis
overexpression of the enzyme in hairy roots of transgenic Anisodus acutangulus using Agrobacterium tumefaciens strain C58C1 transfection method, coexpression with tropinone reductase I
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the gene encoding hyosyamine 6-hydroxylase is placed under the regulation of the CaMV 35S promoter and introduced into the genome of a scopolamine-rich Duboisia hybrid by a binary vector system using Agrobacterium rhizogenes strain LBA9402. The scopolamine levels in the resulting engineered hairy root lines increases up to three times compared to wild-type hairy roots, but there is no clear increase in the engineered regenerated plants
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transformation through Agrobacterium rhizogenes infection
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
trivalent chromium, as KCr(SO4)2, induces the enzyme expression at 1 mM
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
D219H
-
inactive mutant enzyme
D219N
-
inactive mutant enzyme
H217Q
-
inactive mutant enzyme
H66Q
-
mutant enzyme has 97% of the activity of the wild-type enzyme
S274Q
-
inactive mutant enzyme
additional information
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
pharmacology
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tropane alkaloids including hyoscyamine, anisodamine, scopolamine and anisodine, are used medicinally as anticholinergic agents with increasing market demand, improvement of production by metabolic engineering introduction of genes encoding the branch-controlling enzyme tropinone reductase I and the downstream rate-limiting enzyme hyoscyamine-6beta-hydroxylase