Information on EC 1.1.1.138 - mannitol 2-dehydrogenase (NADP+)

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

EC NUMBER
COMMENTARY hide
1.1.1.138
-
RECOMMENDED NAME
GeneOntology No.
mannitol 2-dehydrogenase (NADP+)
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
D-mannitol + NADP+ = D-fructose + NADPH + H+
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
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
Fructose and mannose metabolism
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SYSTEMATIC NAME
IUBMB Comments
D-mannitol:NADP+ 2-oxidoreductase
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CAS REGISTRY NUMBER
COMMENTARY hide
37250-68-3
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ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
strain A5
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Manually annotated by BRENDA team
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-
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Manually annotated by BRENDA team
strain HH-01, KCCM-10252
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Manually annotated by BRENDA team
Cenococcum graniforme
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-
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Manually annotated by BRENDA team
Ceratocystis multiannulata
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-
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Manually annotated by BRENDA team
Diplodia viticola Desm.
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-
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Manually annotated by BRENDA team
strain IFO 12528
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Manually annotated by BRENDA team
NRRL B-3693, enzyme production depends on growth on fructose or sucrose
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Manually annotated by BRENDA team
strain ATCC 53608, gene mdh
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Manually annotated by BRENDA team
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-
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Manually annotated by BRENDA team
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Manually annotated by BRENDA team
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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
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-
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Manually annotated by BRENDA team
strain QM9414 (ATCC 26921), synonym Trichoderma reesei
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Manually annotated by BRENDA team
strain QM9414 (ATCC 26921), synonym Trichoderma reesei
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Manually annotated by BRENDA team
plant symbiotic ascomycete fungus, strain MYA-1019
UniProt
Manually annotated by BRENDA team
biotrophic plant pathogenic rust fungus, gene MAD1
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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-deoxy-6-methyl-D-glucitol + NADP+
1-deoxy-6-methyl-D-glucose + NADPH
show the reaction diagram
-
poorer substrate than D-glucitol
-
?
1-deoxy-6-methyl-D-mannitol + NADP+
1-deoxy-6-methyl-D-fructose + NADPH
show the reaction diagram
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poorer substrate than D-mannitol
-
?
1-deoxy-D-glucitol + NADP+
1-deoxy-D-glucose + NADPH
show the reaction diagram
-
poorer substrate than glucitol
-
?
1-deoxy-D-mannitol + NADP+
1-deoxy-D-fructose + NADPH
show the reaction diagram
-
poorer substrate than D-mannitol
-
?
arabinose + NADPH + H+
arabinitol + NADP+
show the reaction diagram
-
-
-
-
r
D-arabinitol + NADP+
D-xylulose + NADPH + H+
show the reaction diagram
D-fructose + NADPH
D-mannitol + NADP+
show the reaction diagram
D-fructose + NADPH + H+
D-mannitol + NADP+
show the reaction diagram
D-mannitol + 3-acetylpyridine adenine dinucleotide phosphate
D-fructose + 3-acetylpyridine adenine dinucleotide phosphate(H)
show the reaction diagram
-
7.5% of the activity compared to NADP+
-
?
D-mannitol + NAD(P)+
D-fructose + NAD(P)H + H+
show the reaction diagram
D-mannitol + NAD+
D-fructose + NADH + H+
show the reaction diagram
D-mannitol + NADP+
D-fructose + NADPH + H+
show the reaction diagram
D-mannitol + thio-NADP+
D-fructose + thio-NADPH
show the reaction diagram
-
30% of the activity compared to NADP+
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?
D-mannose + NADPH + H+
D-mannitol + NADP+
show the reaction diagram
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-
-
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r
D-sorbitol + NADP+
D-sorbose + NADPH + H+
show the reaction diagram
L-arabinitol + NADP+
L-xylulose + NADPH + H+
show the reaction diagram
L-sorbitol + NADP+
L-sorbose + NADPH
show the reaction diagram
L-sorbitol + NADP+
L-sorbose + NADPH + H+
show the reaction diagram
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21% of the activity with D-mannitol
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r
perseitol + NADP+
? + NADPH
show the reaction diagram
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6% of the activity compared to D-mannitol
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?
ribose + NADPH + H+
ribitol + NADP+
show the reaction diagram
-
-
-
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r
xylose + NADPH + H+
xylitol + NADP+
show the reaction diagram
-
-
-
-
r
additional information
?
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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
D-fructose + NADPH
D-mannitol + NADP+
show the reaction diagram
D-mannitol + NAD(P)+
D-fructose + NAD(P)H + H+
show the reaction diagram
-
-
-
-
r
D-mannitol + NADP+
D-fructose + NADPH + H+
show the reaction diagram
additional information
?
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
NAD(P)+
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NADP+ is the preferred cofactor in the forward reaction
NAD(P)H
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NADPH is the preferred cofactor in the reverse reaction
NAD+
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5-10% of the activity with NADP+
NADH
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5-10% of the activity with NADPH
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Ba2+
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37% activation at 5 mM only in D-mannitol oxidation
Ca2+
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52% activation at 5 mM up to 140% at 10 mM only in D-mannitol oxidation
Cu2+
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increases the intracellular activity of mannitol dehydrogenase 1.6fold
Mn2+
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15% activation at 5 mM only in D-mannitol oxidation
additional information
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1,10-phenanthroline
inhibits 96% at 4 mM, reduction reaction
2-mercaptoethanol
Ca2+
inhibits 21% at 1 mM, reduction reaction
D-fructose
D-mannitol
dithiothreitol
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0.5 mM, complete inhibition
DTT
inhibits 89% at 0.5 mM, reduction reaction
Fe2+
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86% inhibition at 1 mM
glutathione
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0.5 mM, complete inhibition
KCl
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half Vmax/Km at less than 0.1 M due to general ionic strength effect
KNO3
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half Vmax/Km at less than 0.1 M due to general ionic strength effect
L-cysteine
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0.5 mM, complete inhibition
Mg2+
inhibits 19% at 1 mM, reduction reaction
NaCl
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half Vmax/Km at less than 0.1 M due to general ionic strength effect
NADP+
NADPH
p-chloromercuribenzoate
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0.2 mM, complete inhibition
Sn2+
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29% inhibition at 1 mM
additional information
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
EDTA
activates 5% at 5 mM, reduction reaction
additional information
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
385
arabinose
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pH 7.5, 37C
190
D-arabinitol
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0.804 - 1200
D-fructose
560
D-glucitol
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0.46 - 680
D-mannitol
352
D-mannose
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pH 7.5, 37C
9
NAD+
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pH 6.2, 37C, recombinant enzyme
0.24 - 0.612
NADH
0.014 - 0.35
NADP+
0.00525 - 0.1
NADPH
212
ribose
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pH 7.5, 37C
402
xylose
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pH 7.5, 37C
additional information
additional information
-
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0011
Cu2+
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pH 7.5, 37C
183
D-mannitol
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pH 7.5, 37C
188
mannitol
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pH 7.5, 37C
0.18 - 0.21
NADP+
additional information
additional information
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.4
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recombinant enzyme, forward reaction
0.5 - 0.9
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crude enzyme extract, optimization of culture conditions, overview
0.54
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pH 9.0, 30C
0.61
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crude recombinant Escherichia coli cell extract
1
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recombinant enzyme, reverse reaction
3.1
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substrate D-fructose + NADH, pH 7.5, 37C
3.2
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substrate arabinose, pH 7.5, 37C
5.1
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substrate xylose, pH 7.5, 37C
5.2
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substrate ribose, pH 7.5, 37C
6.1
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substrate D-mannose, pH 7.5, 37C
9.1
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substrate D-mannitol, pH 7.5, 37C
124.6
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purified recombinant enzyme
277
purified native enzyme
315
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substrate D-fructose + NADPH, pH 7.5, 37C
331
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pH 5.5, 30C
350
purified native enzyme
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
5.4
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reverse reaction, recombinant enzyme
5.5
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reduction of D-fructose
6 - 8
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reduction of D-fructose
6
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reverse reaction, recombinant enzyme
6.2
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forward reaction, recombinant enzyme
7.3
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50 mM MOPS-KOH buffer
7.5 - 8
reduction reaction
7.8
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assay at
7.9 - 8.1
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D-fructose reduction
7.9 - 8.3
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D-mannitol oxidation
8
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assay at, both reaction directions
8.7 - 8.8
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D-mannitol oxidation
9
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D-mannitol oxidation
9 - 10
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oxidation of D-mannitol
9
oxidation reaction
10
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oxidation of fructose
10.25
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D-mannitol oxidation
10.5
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forward reaction, recombinant enzyme
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
5
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reduction of D-fructose, 35% of maximum activity
5 - 7
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reverse reaction, 81% of maximal activity at pH 5.0, 22% at pH 7.0, 72% at pH 5.6, and 60% at pH 7.4
6 - 9.5
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95% of its maximal activity for 5 min
6.5
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reduction of D-fructose, 50% of maximum activity
8.5 - 11
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sharp decline below pH 8.5 and above pH 11.0, forward reaction, recombinant enzyme
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
22
assay at room temperature, forward reaction
25
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assay at, both reaction directions
35
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reduction of D-fructose
37 - 40
both reaction directions
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
50
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reduction of D-fructose, 44% of maximum activity
60
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reduction of D-fructose, 15% of maximum activity
pI VALUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
4.9
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isoelectric focusing
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
28500
monomer, blue native gel electrophoresis
36400
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PAGE
40000
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gel filtration
50000
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gel filtration
75000
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recombinant enzyme, gel filtration
110000
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gel filtration
112000
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dynamic light scattering
114000
tetramer, blue native gel electrophoresis
115000 - 130000
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gel filtration, rate zonal ultracentrifugation
140000
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gel filtration
142000
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gel filtration
160000
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gel filtration
163000
gel filtration
170000
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gel filtration
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
?
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x * 29000, SDS-PAGE
heterotetramer
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2 * 43000 + 2 * 34500, SDS-PAGE, both subunits have the same amino-terminal amino acid sequence
monomer
tetramer
additional information
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structure-function analysis of enzyme and the family of polyol-specific long-chain dehydrogenases/reductases. G33 is in the N-terminal coenzyme-binding domain, D230 and K295 are at an interdomain segment contributing to the active site in which K295 likely functions as the catalytic general acid/base
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
1.8-2.8 A resolution
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binary complex with NADP+; binary complex with NADP+ at 1.5 A resolution, catalytic triad is assigned to Ser149, Tyr169 and Lys173
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crystal structures of Cladosporium herbarum MtDH in two different conformations is determined
ammonium sulfate precipitation
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pH STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
3.5 - 9.5
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stable within
285855
4.5 - 8
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655118
6
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50 mM MOPS-KOH buffer, after an initial loss of 25% of activity stable for 5 days at 30C
285860
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
30
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50 mM MOPS-KOH buffer, pH 6.0, stable for 5 days
35
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stable up to
53
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20-50% retaining activity after 20 min
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-20C, 10 mM Tris-HCl, pH 7.5, 10 mM 2-mercaptoethanol, 0.05 mM PMSF, 50%, v/v, glycerol, 1 month
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-80C, 50 mM MOPS, pH 7.5, 1 mM DTT, 50 mM NaCl, several weeks
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4C, no loss of activity within 1 month
Diplodia viticola Desm.
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Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
native enzyme 13.4fold by ammonium sulfate fractionation, hydrophobic interaction chromatography, and anion exchange chromatography; purified by standard chromatographic methods
native enzyme from mycelia 368fold by anion exchange chromatography, ultrafiltration, and 2',5'-ADP affinity chromatography
partial
recombinant His6-tagged enzyme from Escherichia coli strain BL21(DE3) by nickel affinity chromatography and ultratfiltration
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to crystalline state, chromatography techniques, crystallization
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to homogeneity, affinity chromatography
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to homogeneity, chromatography techniques
to homogeneity, chromatography techniques, affinity chromatography
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Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
DNA and amino acid sequence determination and analysis, the enzyme shows a carbon responsive transcriptional pattern and is up-regulated when mycelia are transferred to a culture medium containing D-mannitol or D-fructose, quantitative expression and phylogenetic analysis
expressed in E. coli; gene MtDH, DNA and amino acid sequence determination and analysis, expression of His6-tagged enzyme in Escherichia coli strain BL21(DE3)
expressed in Escherichia coli
expression in Escherichia coli
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expression in Pichia pastoris, gene cloning in Escherichia coli
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expression of mutant enzymes in Escherichia coli strain JM109
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gene MAD1, expression analysis in fungal tissue, recombinant expression in yeast
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gene mdh, DNA and amino acid sequence determination and compiational amnipulation, expression of C-terminally His6-tagged enzyme in Escherichia coli strain BL21(DE3)
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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
D69A
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site-directed mutagenesis, the mutant shows an altered cofactor specificity compared to the wild-type enzyme, cf. EC 1.1.1.67, which is switched to NADP(H), NADP(H) is equally utilized as NAD(H)
E68K
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site-directed mutagenesis, the mutant shows an altered cofactor specificity compared to the wild-type enzyme, cf. EC 1.1.1.67, which is switched to NADP(H), NADP(H) is preferred by 10fold over NAD(H)
additional information
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
analysis
biotechnology
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optimization of culture conditions for production of mannitol, best conditions give 213 g/l mannitol from 250 g/l fructose
synthesis