Information on EC 1.4.1.18 - lysine 6-dehydrogenase

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

EC NUMBER
COMMENTARY hide
1.4.1.18
-
RECOMMENDED NAME
GeneOntology No.
lysine 6-dehydrogenase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
L-lysine + NAD+ + H2O = (S)-2-amino-6-oxohexanoate + NADH + H+ + NH3
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
oxidation
-
-
-
-
redox reaction
-
-
-
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reduction
-
-
-
-
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
Biosynthesis of secondary metabolites
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Metabolic pathways
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Tropane, piperidine and pyridine alkaloid biosynthesis
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lysine metabolism
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SYSTEMATIC NAME
IUBMB Comments
L-lysine:NAD+ 6-oxidoreductase (deaminating)
The enzyme is highly specific for L-lysine as substrate, although S-(2-aminoethyl)-L-cysteine can act as a substrate, but more slowly. While the enzyme from Agrobacterium tumefaciens can use only NAD+, that from the thermophilic bacterium Geobacillus stearothermophilus can also use NADP+, but more slowly [1,4].
CAS REGISTRY NUMBER
COMMENTARY hide
89400-30-6
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
traces of activity
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Manually annotated by BRENDA team
-
-
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Manually annotated by BRENDA team
low activity
-
-
Manually annotated by BRENDA team
traces of activity
-
-
Manually annotated by BRENDA team
Bacterium cadaveris, traces of activity
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-
Manually annotated by BRENDA team
Aerobacter aerogenes ICR 0220 and IFO 12059, traces of activity with strain IFO 3319
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-
Manually annotated by BRENDA team
traces of activity in Micrococcus roseus and Micrococcus flavus
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-
Manually annotated by BRENDA team
no activity in Bos taurus
liver
-
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Manually annotated by BRENDA team
no activity in yeast
more than 20 different yeast tested for activity
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-
Manually annotated by BRENDA team
traces of activity
-
-
Manually annotated by BRENDA team
traces of activity
-
-
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
(S)-2-aminoadipate 6-semialdehyde
(S)-2,3,4,5-tetrahydropiperidine-2-carboxylate + H2O
show the reaction diagram
L-lysine + 3-acetylpyridine-NAD+ + H2O
alpha-aminoadipate delta-semialdehyde + NH3 + 3-acetylpyridine-NADH
show the reaction diagram
L-lysine + deamino-NAD+ + H2O
alpha-aminoadipate delta-semialdehyde + NH3 + deamino-NADH
show the reaction diagram
L-lysine + NAD(P)+ + H2O
(S)-2-aminoadipate 6-semialdehyde + NAD(P)H + H+ + NH3
show the reaction diagram
L-lysine + NAD+
alpha-aminoadipate delta-semialdehyde + NH3 + NADH
show the reaction diagram
L-lysine + NAD+ + H2O
2-aminoadipate-6-semialdehyde + NADH + H+ + NH3
show the reaction diagram
-
cyclizes nonenzymatically to DELTA1-piperidine-6-carboxylate
-
?
L-lysine + NAD+ + H2O
alpha-aminoadipate delta-semialdehyde + NH3 + NADH
show the reaction diagram
-
-
-
?
L-lysine + NADP+
2-aminoadipate-6-semialdehyde + NADPH
show the reaction diagram
22% of activity with NAD+
cyclizes nonenzymatically to DELTA1-piperidine-6-carboxylate
-
?
L-lysine + nicotinamide guanine dinucleotide + H2O
alpha-aminoadipate delta-semialdehyde + NH3 + nicotinamide guanine dinucleotide
show the reaction diagram
-
-
-
?
S-(beta-aminoethyl)-L-cysteine + NAD+
?
show the reaction diagram
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
(S)-2-aminoadipate 6-semialdehyde
(S)-2,3,4,5-tetrahydropiperidine-2-carboxylate + H2O
show the reaction diagram
L-lysine + NAD(P)+ + H2O
(S)-2-aminoadipate 6-semialdehyde + NAD(P)H + H+ + NH3
show the reaction diagram
L-lysine + NAD+
alpha-aminoadipate delta-semialdehyde + NH3 + NADH
show the reaction diagram
L-lysine + NAD+ + H2O
2-aminoadipate-6-semialdehyde + NADH + H+ + NH3
show the reaction diagram
Q9AJC6
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cyclizes nonenzymatically to DELTA1-piperidine-6-carboxylate
-
?
additional information
?
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
3-acetylpyridine-NAD+
deamino-NAD+
nicotinamide guanine dinucleotide
-
additional information
-
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
6-amino-n-caproate
inhibition 20% by 10 mM 6-amino-n-caproate
DTNB
-
almost complete inhibition in presence of NAD+, 40% inhibition in presence of L-lysine
HgCl2
L-leucine
inhibition 50% by 10 mM L-leucine
L-norleucine
inhibition 20% by 10 mM L-norleucine
L-ornithine
inhibition 10% by 10 mM L-ornithine
N-ethylmaleimide
p-chloromercuribenzoate
Pb(acetate)2
1 mM, 37% inhibition
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
6-aminocaproate
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D,L-Homolysine
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L-lysine
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increased activity after 10 min preincubation
additional information
-
activiated by many amino acids
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1.32 - 3.13
3-acetylpyridine-NAD+
0.11 - 1.85
deamino-NAD+
0.73 - 5
L-lysine
0.059 - 0.09
NAD+
0.48
NADP+
50C, pH 10.0
0.37
nicotinamide guanine dinucleotide
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Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
4.54
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purified enzyme
7.5
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preincubation in absence of L-lysine
15.7
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preincubation in presence of L-lysine
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7 - 10.8
approx. 35% of maximal activity at pH 7.0, approx. 50% of maximal activity at pH 10.5
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
95
about, recombinant enzyme
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
50 - 95
maximum activity at about 95C and an extraordinary drop off in activity with reduction in temperature, the activity at 50C is only about 1/170th of that at 95C
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
PDB
SCOP
CATH
ORGANISM
UNIPROT
Pyrococcus horikoshii (strain ATCC 700860 / DSM 12428 / JCM 9974 / NBRC 100139 / OT-3)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
39360
predicted from cDNA
42089
2 * 42600, recombinant enzyme, SDS-PAGE, 2 * 42089, amino acid sequence
42239
x * 42239, deduced from nucleotide sequence
42600
2 * 42600, recombinant enzyme, SDS-PAGE, 2 * 42089, amino acid sequence
70000
-
gel filtration
80000
gel filtration, homodimer
97200
recombinant enzyme, gel filtration
160000
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ultracentrifugation in presence of L-lysine
165000
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gel filtration in presence of L-lysine
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
?
x * 42239, deduced from nucleotide sequence
hexamer
6 * 40000 Da, gel filtration, enzyme elutes as a hexamer when a high concentration of L-lysine (10 mM) is supplemented to both the enzyme and the elution buffer
homodimer
2 * 40000 Da, gel filtration
tetramer
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gel filtration and centrifugation in presence of L-lysine
additional information
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
using the hanging drop method
purified recombinant enzyme complexed with NAD+ and a sulfate ion, sitting drop vapor diffusion method, 0.001 ml of 10 mg/ml protein in 100 mM citrate, pH 5.8, 2.1 M ammonium sulfate, and 1 mM NAD+, is mixed with 0.001 ml of reservoir solution, 20C, X-ray diffraction structure determination and analysis at 2.44 A resolution
pH STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
5 - 7.5
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most stable
391533
5 - 12
the purified recombinant enzyme is stable over a wide range of pH values, losing no activity when incubated at pH values between 5.0 and 12 for 30 min at 50C, most stable at pH 10.0
712491
6 - 9
no loss of activity after 30 min at 50C
654286
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
30
at 30C enzyme activity is kept for 3 days and 70% of the activity remains after 7 days
40
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stable for 10 min in absence of L-lysine, unstable above 40C
60
no loss of activity after 10 min at pH 7.2
65
approx. 25% loss of activity after 10 min at pH 7.2 in the absence of 5 mM lysine, no loss of activity in the presence of 5 mM lysine
70
approx. 55% loss of activity after 10 min at pH 7.2
80
complete loss of activity after 10 min at pH 7.2
100
purified recombinant enzyme, half-life is 180 min, the enzyme is highly thermostable and retaining full activity even after incubation for 50 min at 100C at pH 7.5
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
L-lysine stabilizes
-
most stable after preincubation at 40C, pH 5.5-7 for 10 min
-
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
4C, full activity is maintained for 2 months
4C, more than 3 months, no loss of activity
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
enzyme is purified approximately 100fold to homogeneity with a 15% yield
native LysDH, SuperQ-Toyopearl, Red-Sepharose, Gigapite, Cellulofine, recombinant LysDH, Red-Sepharose
refolded recombinant His-tagged wild-type and mutant LysDHs from Escherichia coli strain Rosettagami (DE3) by gel filtration and nickel affinity chromatography
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
cloned and overexpressed in Escherichia coli
expression in Escherichia coli
expression of His-tagged wild-type and mutant LysDHs in Escherichia coli strain Rosettagami (DE3)
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
E168A
site-directed mutagenesis
E168Q
site-directed mutagenesis
R226K
site-directed mutagenesis
Y156F
site-directed mutagenesis
E168A
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site-directed mutagenesis
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E168Q
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site-directed mutagenesis
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R226K
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site-directed mutagenesis
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Y156F
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site-directed mutagenesis
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Renatured/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
His-tagged wild-type and mutant LysDHs after recombinant expression in Escherichia coli inclusion bodies are suspended in 20 mM Tris-HCl, pH 7.5, containing 5 mM 2-mercaptoethanol and 4% Triton X-100, and disrupted by sonication, followed by solubilization in 50 mM Tris-HCl, pH 7.5, containing 5 mM 2-mercaptoethanol, 6 M guanidine HCl, 0.2 M NaCl, and 1 mM EDTA. Refolding in buffer containing 0.1 M Tris-HCl, pH 7.5, 5 mM 2-mercaptoethanol, 0.4 M arginine, 2 mM EDTA, and 0.1 mM phenylmethylsulfonyl fluoride and incubation for 36 h at 4C. Refolded LysDH is heated at 80C for 10 min and clarified by centrifugation
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
analysis
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highly specific determination of L-lysine concentration in serum