Information on EC 1.1.1.218 - morphine 6-dehydrogenase

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The expected taxonomic range for this enzyme is: Eukaryota, Bacteria

EC NUMBER
COMMENTARY hide
1.1.1.218
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RECOMMENDED NAME
GeneOntology No.
morphine 6-dehydrogenase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
morphine + NAD(P)+ = morphinone + NAD(P)H + H+
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
dehydrogenation
-
-
-
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oxidation
-
-
-
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redox reaction
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-
-
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reduction
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-
-
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PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
morphine biosynthesis
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Isoquinoline alkaloid biosynthesis
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Biosynthesis of secondary metabolites
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SYSTEMATIC NAME
IUBMB Comments
morphine:NAD(P)+ 6-oxidoreductase
Also acts on some other alkaloids, including codeine, normorphine and ethylmorphine, but only very slowly on 7,8-saturated derivatives such as dihydromorphine and dihydrocodeine. In the reverse direction, also reduces naloxone to the 6alpha-hydroxy analogue. Activated by 2-mercaptoethanol.
CAS REGISTRY NUMBER
COMMENTARY hide
106640-77-1
deleted Reg.No.
97002-71-6
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ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
strain Hartley
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Manually annotated by BRENDA team
strain Hartley
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-
Manually annotated by BRENDA team
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-
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Manually annotated by BRENDA team
Syrian hamster
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Manually annotated by BRENDA team
Japanese white rabbit
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-
Manually annotated by BRENDA team
Wistar
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-
Manually annotated by BRENDA team
Wistar
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-
Manually annotated by BRENDA team
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
1-indanol + NADP+
1-indanone + NADPH
show the reaction diagram
-
-
-
-
?
3-hydroxyhexobarbital + NADP+
?
show the reaction diagram
-
does not serve as a substrate for guinea pig enzyme
-
-
?
benzenedihydrodiol + NADP+
?
show the reaction diagram
-
-
-
-
?
codeine + NAD(P)+
codeinone + NAD(P)H
show the reaction diagram
codeine + NADP+
codeinone + NADPH
show the reaction diagram
cyclohexene-2-ol + NADP+
cyclohexene-2-one + NADPH
show the reaction diagram
-
-
-
-
?
dihydrocodeine + NADP+
dihydrocodeinone + NADPH
show the reaction diagram
ethylmorphine + NAD(P)+
?
show the reaction diagram
morphine + NAD(P)+
morphinone + NAD(P)H
show the reaction diagram
-
-
-
-
ir
morphine + NADP+
morphinone + NADPH
show the reaction diagram
morphine + NADP+
morphinone + NADPH + H+
show the reaction diagram
nalorphine + NAD(P)+
(5alpha)-3-hydroxy-17-(prop-2-en-1-yl)-7,8-didehydro-4,5-epoxymorphinan-6-one + NAD(P)H + H+
show the reaction diagram
naloxone + NAD(P)H
6alpha-naloxol + NADP+
show the reaction diagram
normorphine + NAD(P)+
?
show the reaction diagram
trans-1,4-decalindiol + NADP+
?
show the reaction diagram
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about 30% of the activity observed with morphine
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-
?
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
codeine + NADP+
codeinone + NADPH
show the reaction diagram
morphine + NADP+
morphinone + NADPH
show the reaction diagram
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
NAD(P)+
NAD(P)H
NADP+
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the Pseudomonas enzyme acts only with NADP+
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1,10-phenanthroline
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-
2,2'-dipyridyl
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5alpha-dihydrotestosterone
5beta-dihydrotestosterone
androsterone
Barbital
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1mM, 68% inhibition
CdCl2
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dithiol modifier, strong competitive inhibitor to cofactor
chenodeoxycholic acid
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0.1 mM, 24% inhibition
cholic acid
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0.1 mM, 10% inhibition
CuSO4
epiandrosterone
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0.1 mM, 77% inhibition
estradiol
indomethacin
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1 mM, 84% inhibition
iodoacetate
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-
Ketamine
lithocholic acid
naloxone
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1mM, 61% inhibition
p-chloromercuribenzoic acid
Phenylarsine oxide
prostaglandin E1
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-
pyrazole
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1 mM, 20% inhibition
quercetin
quercitrin
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testosterone
additional information
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
2-mercaptoethanol
-
reversible
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.12
1-Indanol
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cosubstrate NAD+
0.92
3-hydroxyhexobarbital
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cosubstrate NAD+
0.002
5alpha-androstan-17beta-ol-3-one
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similar values of other 17beta-hydroxysteroids
1.75
benzenedihydrodiol
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cosubstrate NAD+
0.033 - 0.45
codeine
0.12
codeinone
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cosubstrate NADPH
0.54
cyclohexene-2-ol
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cosubstrate NAD+
0.39 - 2.91
Dihydrocodeine
0.4 - 1.54
ethylmorphine
0.12 - 5.5
morphine
0.0022
NADH
-
-
0.35
NADP+
-
-
0.0065
NADPH
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-
0.015 - 0.048
nalorphine
0.27 - 0.44
naloxone
0.044 - 0.64
normorphine
0.009
testosterone
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cosubstrate NAD+
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.08
-
morphine, NADP+
0.21
-
morphine, NAD+
0.43
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morphine, NAD+
0.53
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morphine, NAD+
0.86
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morphine, NADP+
0.9
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naloxone, NADPH
2.67
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morphine, NADP+
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6.2
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with NADH als cofactor, 67 mM sodium phosphate buffer
6.5
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in presence of NADPH reduction of codeinone to codeine, in MOPS buffer
6.8
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with NADPH as cofactor, 67 mM sodium phosphate buffer
8.6
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with NADP+ as cofactor, in glycine-NaCl-NaOH buffer
9.1
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with NADP+ as cofactor, in tricine-NaOH buffer
9.4
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with NAD+ as cofactor, in glycine-NaCl-NaOH buffer
9.5
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with NADP+ as cofactor, in glycine-NaOH buffer, oxidizing the C-6 hydroxy group of morphine and codeine
9.7
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with NAD+ as cofactor, in glycine-NaCl-NaOH buffer
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
30
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enzyme assay
37
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enzyme assay, reduction of naloxone
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
PDB
SCOP
CATH
ORGANISM
UNIPROT
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
29000
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gel filtration
31990
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based on sequence data
36000
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denatured enzyme, SDS-PAGE
38000
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denatured enzyme, SDS-PAGE
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
monomer
pH STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
8
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in 50 mM sodium phosphate buffer + 100 mM 2-mercaptoethanol + NAD+ at least for a week stable at 2-4C
286281
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
2-mercaptoethanol stabilizes
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2-mercaptoethanol stabilizes during purification and storage, removal inactivates, reversible
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dithiothreitol stabilizes
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enzyme stable without 2-mercaptoethanol
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STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-80C, 10% loss of activity over 2 months
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-80C, 20% glycerol, v/v, stable at least four months
2-4C, 50 mM sodium phosphate buffer + 100 mM 2-mercaptoethanol, pH 6., 90% of the activity retained with both NAD+ and NADP+ for a week
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4C, 80% of the activity after a week in 50 mM sodium phosphate buffer, pH 6.0, 100 mM 2-mercaptoethanol, more stable at pH 6.0 than at pH 8.0
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Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
gel filtration, various chromatographic techniques
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
gene encoding morphine dehydrogenase on natural plasmid, expressed in Escherichia coli
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plasmid containing the gene for morphine dehydrogenase: pMDH1.7
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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
C80S
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change of cysteine to serine: significantly improved stability
D47N
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residue modified by site-directed mutagenesis, resulting in substantial loss of activity
K76M
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residue modified by site-directed mutagenesis, resulting in substantial loss of activity
C80S
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change of cysteine to serine: significantly improved stability
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D47N
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residue modified by site-directed mutagenesis, resulting in substantial loss of activity
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K76M
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residue modified by site-directed mutagenesis, resulting in substantial loss of activity
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Y52F
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F is incapable of acting as proton donor /aim: NAD+-dependent morphine dehydrogenase for biotransformation morphine-morphinone-hydromorphine, codeine-hydrocodone respectively (medically useful semisynthetic opiates); residue modified by site-directed mutagenesis, resulting in substantial loss of activity
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