Information on EC 1.5.1.8 - saccharopine dehydrogenase (NADP+, L-lysine-forming)

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The enzyme appears in viruses and cellular organisms

EC NUMBER
COMMENTARY hide
1.5.1.8
-
RECOMMENDED NAME
GeneOntology No.
saccharopine dehydrogenase (NADP+, L-lysine-forming)
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
N6-(L-1,3-dicarboxypropyl)-L-lysine + NADP+ + H2O = L-lysine + 2-oxoglutarate + NADPH + H+
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
oxidation
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-
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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
Biosynthesis of antibiotics
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Biosynthesis of secondary metabolites
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L-lysine degradation XI (mammalian)
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Lysine degradation
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Metabolic pathways
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lysine metabolism
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SYSTEMATIC NAME
IUBMB Comments
N6-(L-1,3-dicarboxypropyl)-L-lysine:NADP+ oxidoreductase (L-lysine-forming)
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CAS REGISTRY NUMBER
COMMENTARY hide
9031-19-0
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ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
ecotype C-24
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Manually annotated by BRENDA team
var. oleifera cv. Samourai
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-
Manually annotated by BRENDA team
mongrels
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Manually annotated by BRENDA team
tabby
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Manually annotated by BRENDA team
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-
-
Manually annotated by BRENDA team
bifunctional lysine-ketoglutarate reductase/saccharopine dehydrogenase, EC 1.5.8 and EC 1.5.9
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Manually annotated by BRENDA team
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Manually annotated by BRENDA team
IAC 165
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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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Manually annotated by BRENDA team
male Wistar strain
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-
Manually annotated by BRENDA team
Wistar strain
-
-
Manually annotated by BRENDA team
Moench
-
-
Manually annotated by BRENDA team
Moench
-
-
Manually annotated by BRENDA team
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-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
physiological function
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gene silencing by RNAi indicates that the tick LKR/SDH plays an integral role in the osmotic regulation of water balance and development of eggs in ovary of engorged females
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
DL-delta-hydroxylysine + 2-oxoglutarate + NADPH
?
show the reaction diagram
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18% of velocity with equimolar concentration of L-lysine
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-
?
L-Lys + 2-oxoglutarate + NADPH
N6-(L-1,3-dicarboxypropyl)-L-lysine + NADP+ + H2O
show the reaction diagram
L-lysine + 2-oxoglutarate + NADH + H+
N6-(L-1,3-dicarboxypropyl)-L-lysine + NAD+ + H2O
show the reaction diagram
L-lysine + 2-oxoglutarate + NADPH
N6-(L-1,3-dicarboxypropyl)-L-lysine + NADP+ + H2O
show the reaction diagram
L-lysine + 2-oxoglutarate + NADPH + H+
N6-(L-1,3-dicarboxypropyl)-L-lysine + NADP+ + H2O
show the reaction diagram
S-2-aminoethyl-L-cysteine + 2-oxoglutarate + NADPH
?
show the reaction diagram
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
L-lysine + 2-oxoglutarate + NADH + H+
N6-(L-1,3-dicarboxypropyl)-L-lysine + NAD+ + H2O
show the reaction diagram
L-lysine + 2-oxoglutarate + NADPH
N6-(L-1,3-dicarboxypropyl)-L-lysine + NADP+ + H2O
show the reaction diagram
L-lysine + 2-oxoglutarate + NADPH + H+
N6-(L-1,3-dicarboxypropyl)-L-lysine + NADP+ + H2O
show the reaction diagram
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
NADP+
additional information
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(NH4)2SO4
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1 mM, 71% inhibition
Alkaline phosphatase
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CaCl2
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3 mM, 28% loss of activity
cadaverine
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3 mM, 26% loss of activity
Calmidazolium
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0.04 mM, almost complete inhibition of Ca2+-dependent enhancement of enzyme activity, calmodulin antagonist
Carbamoylphosphate
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3 mM, 25% loss of activity
CoCl2
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1 mM, 82% loss of activity
CuSO4
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1 mM, 87% loss of activity
Detergent
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e.g. Aerosol 22, Ultrawet 60L, deoxycholic acid, cetyltrimethyl ammonium bromide, complete inactivation
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DL-pipecolic acid
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6 mM, 47% loss of activity
HgCl2
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0.01 mM, 89% loss of activity
hydroxylamine
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3 mM, 33% loss of activity
L-Glutamic acid
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3 mM, 40% loss of activity
L-Homocitrulline
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3 mM, 49% loss of activity
L-Lysine-p-nitroanilide
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inhibition noncompetitive with L-lysine, competitive with 2-oxoglutarate
L-Lysylglycine
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3 mM, 25% loss of activity
L-ornithine
leucine
MgSO4
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1 mM, 79% loss of activity
MnCl2
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1 mM, 52% loss of activity
N-(6-Aminohexyl)-5-chloro-1-naphthalenesulfonamide
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1.5 mM, almost complete inhibition of Ca2+-dependent enhancement of enzyme activity, calmodulin antagonist
S-2-aminoethyl-L-cysteine
saccharopine
tryptophan
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complete inhibition of saccharopine formation
ZnCl2
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3 mM, complete inhibition
additional information
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
abscisic acid
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0.05 mM, incubation for 12 h, significantly increased activity
EDTA
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1 mM, slight activation, effect not consistant
L-lysine
organic solvent
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polyethylene glycol 6000
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enzyme activity increases in response to an upshock osmotic stress caused by polyethylene glycol 6000 solutions of decreasing osmotic potential with values ranging from -0.1 to -3 MPa
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Tris/HCl
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enzyme activity increases 6fold when the concentration of Tris/HCl is increased from 25 to 200 mM, effect is due to decreased water activity which could induce conformational modification in LOR domain of enzyme
Triton X-100
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1%, slight activation, effect not consistant
additional information
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.79 - 3.7
2-oxoglutarate
0.4 - 13.7
L-lysine
0.032 - 0.08
NADPH
17
S-2-aminoethyl-L-cysteine
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
additional information
additional information
Oryza sativa
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lower turnover number with S-2-aminoethyl-L-cysteine as substrate than with L-lysine
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Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
2
saccharopine
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
1.273
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4.98
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lysine 2-oxoglutarate reductase activity
17.1
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additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6.5 - 7
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His-tagged LKRp, L-lysine catabolic activity
6.7 - 7
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8.4
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saccharopine formation
9
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L-lysine formation
9.5
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L-lysine anabolic activity
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6.2 - 8.6
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pH 6.2: about 50% of activity maximum, pH 8.6: about 60% of activity maximum
6.5 - 9.5
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pH 6.5: about 60% of maximal activity, pH 9.5: about 60% of maximal activity
7.2 - 8.8
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about 50% of activity maximum at pH 7.2 and 8.8
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
23
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assay at
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
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low enzyme concentration
Manually annotated by BRENDA team
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LKR mRNA is highly abundant in ovules and vascular tissue of anther filaments
Manually annotated by BRENDA team
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breast
Manually annotated by BRENDA team
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low enzyme concentration
Manually annotated by BRENDA team
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low enzyme concentration
Manually annotated by BRENDA team
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
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enzyme found only in the mitochondrial matrix
Manually annotated by BRENDA team
additional information
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not found in peroxisomes or lysosomes
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Manually annotated by BRENDA team
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
52000
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4 * 52000, enzyme clearly separated from saccharopine dehydrogenase EC 1.5.1.9, SDS-PAGE
115000
117000
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x * 117000, bifunctional protein with lysine-ketoglutarate reductase EC 1.5.1.8 and saccharopine dehydrogenase EC 1.5.1.9 activities, calculated from cDNA sequence
123000
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2 * 123000, bifunctional protein with lysine-ketoglutarate reductase EC 1.5.1.8 and saccharopine dehydrogenase EC 1.5.1.9 activities, additional 100 kDa band is a proteolytic cleavage product, SDS-PAGE
125000
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2 * 125000, bifunctional enzyme with lysine-oxoglutarate reductase EC 1.5.1.8 and saccharopine dehydrogenase EC 1.5.1.9 activities, digestion with elastase separates the functional domains into a 65 kDa polypeptide with LOR activity and a 57 kDa polypeptide with SDH activity, SDS-PAGE
190000
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bifunctional enzyme lysine 2-oxoglutarate reductase-saccharopine dehydrogenase, gel filtration
202000
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non-denaturing PAGE, bifunctional protein containing lysine-oxoglutarate reductase EC 1.5.1.8 and saccharopine dehydrogenase EC 1.5.1.9 activities, one band represents the holoenzyme and shows higher enzyme activities compared to a second band of 396 kDa with much lower enzyme activities indicating a multimeric structure
203000
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gel filtration, bifunctional protein containing lysine-oxoglutarate reductase EC 1.5.1.8 and saccharopine dehydrogenase EC 1.5.1.9 activities
230000
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gel filtration
256000
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gel filtration, bifunctional protein with lysine-ketoglutarate reductase EC 1.5.1.8 and saccharopine dehydrogenase EC 1.5.1.9 activities
260000
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bifunctional enzyme with lysine-oxoglutarate reductase EC 1.5.1.8 and saccharopine dehydrogenase EC 1.5.1.9 activities, but domains are functionally independent of each other
420000
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sedimentation equilibrium method, single protein with lysine-ketoglutarate reductase EC 1.5.1.8 and saccharopine dehydrogenase EC 1.5.1.9 activities: aminoadipic semialdehyde synthase, but reductase and dehydrogenase domains are separately folded and functionally independent of each other
467000
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gel filtration, single protein catalyzes both lysine-ketoglutarate reductase reaction EC 1.5.1.8 and saccharopine dehydrogenase reaction EC 1.5.1.9, bifunctional enzyme: aminoadipic semialdehyde synthase
468000
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gel filtration, single protein catalyzes both lysine-ketoglutarate reductase reaction EC 1.5.1.8 and saccharopine dehydrogenase reaction EC 1.5.1.9, bifunctional enzyme: aminoadipic semialdehyde synthase
480000
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gel filtration, no separation of L-lysine-ketoglutarate reductase EC 1.5.1.8 and saccharopine dehydrogenase EC 1.5.1.9
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
?
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x * 117000, bifunctional protein with lysine-ketoglutarate reductase EC 1.5.1.8 and saccharopine dehydrogenase EC 1.5.1.9 activities, calculated from cDNA sequence
homodimer
homotetramer
additional information
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phosphoprotein
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active bifunctional enzyme is a phosphoprotein, phosphorylation is essential for LKR activity, but not for SDH activity, incubation with casein kinase II results in a significant phosphorylation of the bifunctional enzyme
additional information
-
enzyme may be activated by post-translational modification
pH STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
4.4
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10 min, 50% loss of activity
392361
4.6 - 4.9
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10 min, stable
392361
7.5
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4C, in presence of 5 mM 2-mercaptoethanol and 0.1 mM EDTA, highest stability
392360
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
40
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10 min, unstable above
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
EDTA and 2-mercaptoethanol stabilize during purification
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lysine 2-oxoglutarate reductase activity is very unstable during purification, following ion-exchange chromatography
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presence of 5% w/v insoluble polyvinylpyrrolidone and 10% v/v glycerol in extraction buffer and glycerol in running buffers is crucial to maintain enzyme activity
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stabilization of holoenzyme by high salt concentrations, e.g. KCl
Triton X-100 is necessary to observe maximal enzyme activity
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very unstable during the isolation and purification procedure
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STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-20C, 1 month, 50% loss of activity
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-20C, 2 months, no loss of activity
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-25C, 1 month, stable
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-70C, 6 months, stable
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0C, 10 mM Tris-HCl buffer, pH 7.6, 5 mM 2-mercaptoethanol, 0.1 mM EDTA, stable
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4C, pH 7.5, 5 mM 2-mercaptoethanol, 0.1 mM EDTA, storage conditions which are most effective in preserving enzyme activity
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Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
1630.5fold purification of a bifunctional protein containing lysine-ketoglutarate reductase EC 1.5.1.8 and saccharopine dehydrogenase EC 1.5.1.9 activities
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300fold purification, enzyme clearly separated from saccharopine dehydrogenase EC 1.5.1.9
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38fold purification; partial purification of a single bifunctional protein with lysine-2-oxoglutarate reductase EC 1.5.1.8 and saccharopine dehydrogenase EC 1.5.1.9 activities
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44.6fold partial purification from liver
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450fold purification, no separation of lysine-ketoglutarate reductase EC 1.5.1.8 and saccharopine dehydrogenase EC 1.5.1.9
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500fold purification of a single protein with lysine-ketoglutarate reductase EC 1.5.1.8 and saccharopine dehydrogenase EC 1.5.1.9 activities
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9.6fold partial purification from liver
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partial purification
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partial purification of a recombinant bifunctional protein with lysine-2-oxoglutarate reductase EC 1.5.1.8 and saccharopine dehydrogenase EC 1.5.1.9 activities and of the monofunctional lysine-2-oxoglutarate reductase domain
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partial purification of a single bifunctional protein with lysine-2-oxoglutarate reductase EC 1.5.1.8 and saccharopine dehydrogenase EC 1.5.1.9 activities
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partial purification of bifunctional enzyme with lysine-oxoglutarate reductase EC 1.5.1.8 and saccharopine dehydrogenase EC 1.5.1.9 activities
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separation of lysine-ketoglutarate reductase and saccharopine dehydrogenase activities by limited proteolysis with elastase, chymotrypsin, and papain; single protein with lysine-ketoglutarate reductase EC 1.5.1.8 and saccharopine dehydrogenase EC 1.5.1.9 activities: aminoadipic semialdehyde synthase
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single protein with lysine-ketoglutarate reductase EC 1.5.1.8 and saccharopine dehydrogenase EC 1.5.1.9 activities: aminoadipic semialdehyde synthase
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Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
bifunctional LKR/SDH cDNA and monofunctional LKR cDNA are cloned, expression in Saccharomyces cerevisiae mutant lys1, but LKR cannot complement yeast LKR null mutant because of its uni-directional catabolic activity, overexpression in wild type yeast
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cloning of cDNA encoding the bifunctional protein with lysine 2-oxoglutarate reductase EC 1.5.1.8 and saccharopine dehydrogenase EC 1.5.1.9 activities, expression of the single gene is subject to spatial and developmental controls, expression in Escherichia coli produces no active LKR, perhaps because of a missing post-translational modification in prokaryotes, expression in Saccharomyces cerevisiae mutant lys1
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gene lys1 encoding lysine 2-oxoglutarate reductase is cloned
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genes encoding bifunctional protein with lysine 2-oxoglutarate reductase EC 1.5.1.8 and saccharopine dehydrogenase EC 1.5.1.9 activities are cloned
isolation and cloning of the cDNA and single copy gene encoding bifunctional enzyme with lysine-ketoglutarate reductase EC 1.5.1.8 and saccharopine dehydrogenase EC 1.5.1.9, no expression in Escherichia coli, gene product with amino domain corresponding to LKR and carboxy domain corresponding to SDH
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isolation of the cDNA and gene encoding bifunctional enzyme with lysine-ketoglutarate reductase EC 1.5.1.8 and saccharopine dehydrogenase EC 1.5.1.9 activities
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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine