Information on EC 1.5.1.7 - saccharopine dehydrogenase (NAD+, L-lysine-forming)

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The enzyme appears in viruses and cellular organisms

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EC NUMBER
COMMENTARY hide
1.5.1.7
-
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RECOMMENDED NAME
GeneOntology No.
saccharopine dehydrogenase (NAD+, L-lysine-forming)
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REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
N6-(L-1,3-dicarboxypropyl)-L-lysine + NAD+ + H2O = L-lysine + 2-oxoglutarate + NADH + H+
show the reaction diagram
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
oxidation
-
-
-
-
redox reaction
-
-
-
-
reduction
-
-
-
-
reductive condensation
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PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
L-lysine biosynthesis IV
-
-
lysine metabolism
-
-
Lysine biosynthesis
-
-
Lysine degradation
-
-
Metabolic pathways
-
-
Biosynthesis of secondary metabolites
-
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Biosynthesis of antibiotics
-
-
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SYSTEMATIC NAME
IUBMB Comments
N6-(L-1,3-dicarboxypropyl)-L-lysine:NAD+ oxidoreductase (L-lysine-forming)
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CAS REGISTRY NUMBER
COMMENTARY hide
9073-96-5
-
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
metabolism
-
saccharopine dehydrogenase is the last enzyme in the alpha-aminoadipate pathway of L-lysine biosynthesis
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SUBSTRATE
PRODUCT                       
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
N6-(L-1,3-dicarboxypropyl)-L-lysine + NAD+ + 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 + alpha-ketoadipate + NADH
?
show the reaction diagram
-
-
-
-
?
L-lysine + alpha-ketobutyrate + NADH
?
show the reaction diagram
-
-
-
-
?
L-lysine + alpha-ketomalonate + NADH
?
show the reaction diagram
-
-
-
-
?
L-lysine + alpha-ketovalerate + NADH
?
show the reaction diagram
-
-
-
-
?
L-lysine + glyoxylate + NADH
?
show the reaction diagram
-
-
-
-
?
L-lysine + pyruvate + NADH
?
show the reaction diagram
-
-
-
-
?
N6-(L-1,3-dicarboxypropyl)-L-lysine + NAD+ + H2O
L-lysine + 2-oxoglutarate + NADH
show the reaction diagram
N6-(L-1,3-dicarboxypropyl)-L-lysine + NAD+ + H2O
L-lysine + 2-oxoglutarate + NADH + H+
show the reaction diagram
additional information
?
-
-
3-acetylpyridine adenine dinucleotide, 3-pyridinealdehyde adenine dinucleotide, and thionicotinamide adenine dinucleotide can serve as a substrate in the oxidative deamination reaction, as can glyoxylate, pyruvate, alpha-ketobutyrate, alpha-ketovalerate, alpha-ketomalonate, and alpha-ketoadipate in the reverse reaction
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-
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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
N6-(L-1,3-dicarboxypropyl)-L-lysine + NAD+ + H2O
show the reaction diagram
-
-
-
-
r
L-lysine + 2-oxoglutarate + NADH + H+
N6-(L-1,3-dicarboxypropyl)-L-lysine + NAD+ + H2O
show the reaction diagram
-
-
-
-
r
N6-(L-1,3-dicarboxypropyl)-L-lysine + NAD+ + H2O
L-lysine + 2-oxoglutarate + NADH
show the reaction diagram
N6-(L-1,3-dicarboxypropyl)-L-lysine + NAD+ + H2O
L-lysine + 2-oxoglutarate + NADH + H+
show the reaction diagram
-
-
-
-
r
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
NADPH
-
NADPH can substitute for NADH
additional information
-
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Cu2+
-
4% of control activity at 1 mM
Hg2+
-
complete inhibition at 1 mM
Mn2+
-
46% of control activity at 1 mM
Sn2+
-
11% of control activity at 1 mM
Zn2+
-
66% of control activity at 1 mM
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INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
2',3'-cyclic NADP
-
-
2',3'-cyclic NADP+
-
-
2,3-Butanedione
-
protection by L-leucine, NADH and 2-oxoglutarate
2-oxoglutarate
5,5'-dithiobis(2-nitrobenzoate)
-
-
adenosine
alpha-ketoadipate
-
-
alpha-ketoglutarate
alpha-ketoisovalerate
-
-
alpha-ketomalonate
-
-
alpha-ketopimelate
-
-
amino acids
diethyldicarbonate
-
-
iodoacetamide
-
-
iodoacetate
L-isoleucine
L-leucine
L-lysine
L-methionine
-
-
L-norleucine
L-ornithine
lysine
-
substrate inhibition
N-Butylmaleimide
-
-
N-ethylmaleimide
-
-
NADP+
-
NADP+ is competitive versus NADPH when NADPH serves as the coenzyme
o-Iodosobenzoate
-
-
oxaloacetate
-
-
oxalylglycine
p-chloromercuribenzoate
-
-
p-hydroxymercuribenzoate
pyridine 2,3-dicarboxylate
-
-
Pyridine 2,4-dicarboxylate
-
-
pyridoxal 5'-phosphate
-
reversible inactivation
saccharopine
-
product inhibition, uncompetitive versus NADH
additional information
-
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.11 - 267
2-oxoglutarate
5.3
alpha-ketoadipate
-
at pH 7.0
153
alpha-Ketobutyrate
-
at pH 7.0
24
alpha-ketomalonate
-
at pH 7.0
94
alpha-ketovalerate
-
at pH 7.0
6.4
glyoxylate
-
at pH 7.0
0.62 - 267
L-lysine
0.2 - 14
N6-(L-1,3-Dicarboxypropyl)-L-lysine
0.1 - 3.3
NAD+
0.01 - 0.46
NADH
4.1
pyruvate
-
at pH 7.0
1.67
saccharopine
-
-
additional information
additional information
-
detailed kinetic analysis including pH-dependance and deuterium kinetic effects
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
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Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1.5
2',3'-cyclic NADP
-
at pH 7.0
0.42
adenosine
-
at pH 7.0
50
adipate
-
at pH 7.0
0.093
ADP
-
at pH 7.0
0.29
ADP-ribose
-
at pH 7.0
5.3
alpha-ketoadipate
-
at pH 7.0
0.6 - 28
alpha-ketoglutarate
36
alpha-ketoisovalerate
-
at pH 7.0
24
alpha-ketomalonate
-
at pH 7.0
18
alpha-ketopimelate
-
at pH 7.0
0.055
AMP
-
at pH 7.0
5.5
D-Lysine
-
at pH 7.0
1
Glutarate
-
at pH 7.0
16.4
L-arginine
-
at pH 7.0
16
L-glutamine
-
at pH 7.0
22
L-isoleucine
-
at pH 7.0
0.125 - 5.6
L-leucine
1.1 - 27.8
L-lysine
3.12
L-methionine
-
at pH 7.0
1.13
L-norvaline
-
at pH 7.0
5
L-ornithine
-
at pH 7.0
140
L-valine
-
at pH 7.0
24
malonate
-
at pH 7.0
0.5 - 1.9
NAD+
0.015 - 0.038
NADH
1.2
NADP
-
at pH 7.0
3.5
NADP+
-
at pH 7.0
7.2
NMN
-
at pH 7.0
36
oxalate
-
at pH 7.0
6.4
oxaloacetate
-
at pH 7.0
0.1
oxalylglycine
-
at pH 7.0
18.3
pyridine 2,3-dicarboxylate
-
at pH 7.0
1.1
Pyridine 2,4-dicarboxylate
-
at pH 7.0
21
succinate
-
at pH 7.0
additional information
additional information
-
inhibition studies with substrates analogues
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.1
-
crude extract
0.381
-
crude extract, strain Wis 54-1255
0.402
-
crude extract, strain HS1
0.45
-
crude extract, mutant strain 7.2
0.571
-
crude extract, mutant strain 10.25
24.6
-
after purification
106
-
after purification
additional information
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6.8
-
L-lysine + 2-oxoglutarate + NADH
7.1
-
saccharopine + NAD+ + H2O
10
-
or higher, saccharopine + NAD+ + H2O
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pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
5.2 - 9
-
half-maximal activities at pH 5.2 and 9.0, L-lysine + 2-oxoglutarate + NADH
5.6 - 7.8
-
half-maximal activities at pH 5.6 and 7.8
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
40
-
increase of activity from 20°C to 40°C
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TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
20 - 40
-
increase of activity from 20°C to 40°C
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PDB
SCOP
CATH
ORGANISM
UNIPROT
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Streptococcus pneumoniae serotype 2 (strain D39 / NCTC 7466)
Wolinella succinogenes (strain ATCC 29543 / DSM 1740 / LMG 7466 / NCTC 11488 / FDC 602W)
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MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
38000 - 40000
-
gel filtration, sedimentation equilibrium centrifugation, SDS-PAGE
39000
-
1 * 39000, SDS-PAGE
41464
-
x * 41464, calculated from amino acid sequence
49000
-
sucrose density gradient centrifugation
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SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
?
-
x * 41464, calculated from amino acid sequence
monomer
-
1 * 39000, SDS-PAGE
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Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
in complex with NAD+ and saccharopine, hanging drop vapour diffusion method in 20% (w/v) PEG 8000, 0.1 M MES (pH 6.0), and 0.2 M Ca(OAc)2
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mutant enzyme C205S, hanging drop vapor diffusion method, using 100 mM Tris (pH 7.0), 30% (w/v) PEG-MME 2000 at 4°C
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the apo-enzyme is obtained using the hanging drop vapour diffusion method with 100 mM Tris (pH 7.0) and 22% (w/v) PEG 8000, sulfate-, AMP-, and oxalylglycine-bound enzyme crystals are obtained by the hanging drop vapour diffusion method with 26% (w/v) PEG-MME 2000 in 100 mM Tris (pH 7.0) containing 200 mM (NH4)2SO4, or with 24% (w/v) PEG-MME 2000 in 100 mM Bis-Tris, pH 6.5, or with 24% (w/v) PEG-MME 2000 in 100 mM Tris, pH 8.0, at 4°C, respectively
-
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pH STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
5 - 8
-
-
396553
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GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
2-mercaptoethanol, 1 mM, stabilizes
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bovine serum albumin stabilizes
-
high salt concentration stabilizes
-
KCl, above 0.1 M stablizes
-
unstable at enzyme concentration below 0.1 mg protein/ml
-
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STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-20°C, protein concentration above 0.1 mg/ml, pH 6.8, 1 mM EDTA, several months
-
4°C, His-tagged mutant enzymes in 100 mM HEPES, 300 mM KCl and 300 mM imidazole at pH 8.0, several months, the mutant enzymes maintain stability and remain active
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4°C, mutant enzymes in 100 mM HEPES, 300 mM KCl, and 300 mM imidazole at pH 8.0, several months, no loss of activity
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Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
glutathione Sepharose column chromatography
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Ni-NTA affinity column chromatography
-
Ni-NTA column chromatography
-
Ni2+-NTA column chromatography
-
Ni–NTA affinity column chromatography
-
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Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expressed in Escherichia coli B834(DE3) cells
-
expressed in Escherichia coli BL21 (DE3)-RIL cells
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expressed in Escherichia coli BL21(DE3)-RIL cells
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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
C205S
-
the Km for N6-(L-1,3-dicarboxypropyl)-L-lysine decreases by more than 30fold for the C205S mutant
C205V
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the Km for N6-(L-1,3-dicarboxypropyl)-L-lysine decreases by 5fold for the C205V mutant
E122A
-
mutation increases the positive charge of the active site and affects the pKa value of the catalytic group. Kinetic mechanism similar to wild-type
E122Q
-
mutation increases the positive charge of the active site and affects the pKa value of the catalytic group. Kinetic mechanism similar to wild-type
E16Q/C205S
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the mutation decreases the turnover number by about 15fold
E78A
-
mutation increases the positive charge of the active site and affects the pKa value of the catalytic group. Kinetic mechanism differs from wild-type, 2-oxoglutarate binds to enzyme and enzyme-NADH
E78A/E122A
-
mutation increases the positive charge of the active site and affects the pKa value of the catalytic group. Kinetic mechanism similar to wild-type
E78Q
-
mutation increases the positive charge of the active site and affects the pKa value of the catalytic group. Kinetic mechanism similar to wild-type
E78Q/E122Q
-
mutation increases the positive charge of the active site and affects the pKa value of the catalytic group. Kinetic mechanism similar to wild-type
H96Q
-
the mutation results in 100 and more than 1000fold increases in Km values for L-lysine and 2-oxoglutarate, respectively
K13M/C205S
-
the mutation decreases the turnover number by about 15fold
K77M
-
the mutation results in 28 and 90fold increases in Km values for L-lysine and 2-oxoglutarate, respectively
K77M/H96Q
-
the mutations result in 300 and 80fold increases in Km values for L-lysine and 2-oxoglutarate, respectively
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine
-
target for antimicrobial drug development
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Show AA Sequence (1120 entries)
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LINKS TO OTHER DATABASES (specific for EC-Number 1.5.1.7)
ExplorEnz
ExPASy
KEGG
MetaCyc
SABIO-RK
NCBI: PubMed, Protein, Nucleotide, Structure, Genome, OMIM
IUBMB Enzyme Nomenclature
PROSITE Database of protein families and domains
InterPro (database of protein families, domains and functional sites)