Information on EC 1.2.1.79 - succinate-semialdehyde dehydrogenase (NADP+)

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

EC NUMBER
COMMENTARY hide
1.2.1.79
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RECOMMENDED NAME
GeneOntology No.
succinate-semialdehyde dehydrogenase (NADP+)
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
succinate semialdehyde + NADP+ + H2O = succinate + NADPH + 2 H+
show the reaction diagram
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PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
4-aminobutanoate degradation II
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4-hydroxyphenylacetate degradation
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Alanine, aspartate and glutamate metabolism
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Butanoate metabolism
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Metabolic pathways
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Nicotinate and nicotinamide metabolism
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nicotine degradation I (pyridine pathway)
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nicotine degradation II (pyrrolidine pathway)
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TCA cycle IV (2-oxoglutarate decarboxylase)
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glutamate and glutamine metabolism
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SYSTEMATIC NAME
IUBMB Comments
succinate-semialdehyde:NADP+ oxidoreductase
This enzyme participates in the degradation of glutamate and 4-aminobutyrate. It is similar to EC 1.2.1.24 [succinate-semialdehyde dehydrogenase (NAD+)], and EC 1.2.1.16 [succinate-semialdehyde dehydrogenase (NAD(P)+)], but is specific for NADP+. The enzyme from Escherichia coli is 20-fold more active with NADP+ than NAD+ [2].
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
metabolism
physiological function
gene is disrupted in a transposon-induced mutant of Ralstonia eutropha exhibiting the phenotype 4-hydroxybutyric acid-leaky
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
2,5-dioxopentanoate + NAD+ + H2O
?
show the reaction diagram
2,5-dioxopentanoate + NADP+ + H2O
?
show the reaction diagram
3-carboxybenzaldehyde + NADP+ + H2O
3-carboxybenzoate + NADPH + 2 H+
show the reaction diagram
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-
-
?
3-nitrobenzaldehyde + NADP+ + H2O
3-nitrobenzoate + NADPH + 2 H+
show the reaction diagram
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-
-
?
4-carboxybenzaldehyde + NADP+ + H2O
4-carboxybenzoate + NADPH + H+
show the reaction diagram
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-
-
?
benzaldehyde + NADP+ + H2O
benzoate + NADPH + 2 H+
show the reaction diagram
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-
-
?
malonate semialdehyde + NADP+ + H2O
malonate + NADPH + 2 H+
show the reaction diagram
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8.7% of the activity with succinate semialdehyde
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-
?
n-butanal + NADP+ + H2O
butanoate + NADPH + 2 H+
show the reaction diagram
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-
-
?
n-hexanal + NADP+ + H2O
hexanoate + NADPH + H+
show the reaction diagram
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-
-
?
n-pentanal + NADP+ + H2O
n-pentanoate + NADPH + H+
show the reaction diagram
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-
-
?
succinate semialdehyde + NAD+ + H2O
succinate + NADH + 2 H+
show the reaction diagram
succinate semialdehyde + NAD+ + H2O
succinate + NADH + H+
show the reaction diagram
succinate semialdehyde + NADP+ + H2O
succinate + NADPH + 2 H+
show the reaction diagram
succinate semialdehyde + NADP+ + H2O
succinate + NADPH + H+
show the reaction diagram
succinic semialdehyde + NADP+ + H2O
succinate + NADPH + 2 H+
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
succinate semialdehyde + NAD+ + H2O
succinate + NADH + H+
show the reaction diagram
succinate semialdehyde + NADP+ + H2O
succinate + NADPH + 2 H+
show the reaction diagram
succinate semialdehyde + NADP+ + H2O
succinate + NADPH + H+
show the reaction diagram
succinic semialdehyde + NADP+ + H2O
succinate + NADPH + 2 H+
show the reaction diagram
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
additional information
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Ca2+
2 to 3-fold activation at saturating concentration
Co2+
2 to 3-fold activation at saturating concentration
K+
-
5 mM, 10% activation
Mg2+
2 to 3-fold activation at saturating concentration
Mn2+
2 to 3-fold activation at saturating concentration
Ni2+
2 to 3-fold activation at saturating concentration
additional information
no activation with Cd2+ or Zn2+
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
3-tolualdehyde
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only the aldehyde forms and not the gem-diol forms of the inhibitor 3-tolualdehyde bind to the enzyme
5,5'-dithiobis(2-nitrobenzoic acid)
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0.01 mM, 29% residual activity
H2O2
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50 microM H2O2 sharply reduces activity to 31% of the H2O2-free enzyme and activity further decreases to 3% at 1 mM H2O2
N-ethylmaleimide
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0.1 mM, complete loss of activity
NADPH
succinate semialdehyde
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substrate inhibition above 1 mM
Succinic semialdehyde
partial substrate inhibition because velocity decreases to a non-zero value at saturating concentrations of Mg2+ and succinic semialdehyde
Zn2+
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1 mM, complete inhibition
additional information
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
2-mercaptoethanol
dithiothreitol
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.1 - 0.2
2,5-dioxopentanoate
11.1
NAD+
pH 6.5, 70C
0.0092 - 0.439
NADP+
0.001 - 1.06
succinate semialdehyde
0.003 - 0.0133
Succinic semialdehyde
additional information
additional information
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
21.2 - 27.3
2,5-dioxopentanoate
136.3
NAD+
Sulfolobus solfataricus
Q97XA5
pH 6.5, 70C
1.3 - 16.5
NADP+
16.8 - 18.4
succinate semialdehyde
1.9 - 4.7
Succinic semialdehyde
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
134.1 - 215.3
2,5-dioxopentanoate
3305
12.3
NAD+
Sulfolobus solfataricus
Q97XA5
pH 6.5, 70C
7
21 - 3066
NADP+
10
1789 - 3454
succinate semialdehyde
528
140 - 1600
Succinic semialdehyde
809
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0628
Succinic semialdehyde
partial substrate inhibition, pH 7.5 and 37C
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.08
3-tolualdehyde
Escherichia coli
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pH 8.5, 22C
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
4.1
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pH 7.8, 30C
7.9
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pH 8.7, 35C
14.9
cosubstrate NAD+, pH 11.0, 30C
34
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pH 8.5, 22C
132.1
cosubstrate NADP+, pH 11.0, 30C
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
5.5 - 10
GabD1 could not be assayed below pH 5.5, due to precipitation and loss of activity
7.4
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75% of maximum activity
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
22
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assay at
35 - 45
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LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
5022
x * 5022, calculated, x * 51000, SDS-PAGE
50000
2 * 50000, SDS-PAGE
51000
x * 5022, calculated, x * 51000, SDS-PAGE
51600
2 * 51600, calculated from sequence
60000
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x * 60000, calculated
91000
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analytical ultracentrifugation
114000
gel filtration
200000
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gel filtration
300000
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gel filtration
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
dimer
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Sp2771 monomer is composed of N-terminal cofactor binding domain, a catalytic domain and an oligomerization domain
homodimer
tetramer
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
in complex with NADP+, hanging drop vapour diffusion method, using 0.2 M ammonium tartrate, 26-31% polyethylene glycol 3350, 10 mM beta-mercaptoethanol and 0.1 M Tris (pH 7.2-7.5)
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to 1.4 A resolution. The overall structure of SSADH shares the general fold of ALDH classes 1 and 2. The SSADH monomer is composed of three domains; an N-terminal NAD(P)-binding domain of residues 1125, 148256, and 457472, a catalytic domain of residues 257456, and an oligomerization domain of residues 126147 and 473482. The catalytic loop of Escherichia coli SSADH, unlike that of human SSADH, does not undergo disulfide bond-mediated structural changes upon changes of environmental redox status. The protein is not regulated via redox-switch modulation. A difference in the conformation of the connecting loop beta15beta16 causes the formation of a water molecule-mediated hydrogen bond network between the connecting loop and the catalytic loop in Escherichia coli SSADH
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comparison to human enzyme, analysis of NADP+ binding site. Enzyme is a homotetramer with the 4 monomers related by a non-crystallographic 222 symmetry. The conserved catalytic site residues and active site residues correspond to C288 and E254 as well as R164, R282 and S445, respectively
crystal structures of SySSADH determined in their apo form, as a binary complex with NADP+ and as a ternary complex with succinic semialdehyde and NADPH, resoultion of 1.7 A for the apo form and of 1.4 A for the binary and ternary complex
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crystal structures of wild type Sp2771 at 2.1 A resolution, Sp2771 S419A mutant at 2.5 A resolution and ternary structure of non-catalytic Sp2771 C262A mutant in complex with NADP + and succinate semialdehyde at 1.7 A resolution
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pH STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
8
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rapid decrease in stability above
707580
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
18
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14 h, 78% residual activity
37
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14 h, 69% residual activity
50
10 min, stable
60
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stable up to
OXIDATION STABILITY
ORGANISM
UNIPROT
LITERATURE
GabD1 is naturally resistant to oxidation by H2O2
724115
SySSADH is an oxidation-sensitive enzyme and the formation of the NADP-cysteine adduct is a kinetically preferred event that protects the catalytic Cys-262 from H2O2-dependent oxidative stress
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725523
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-15C, 14 h, 81% residual activity
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18C, 14 h, 78% residual activity
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5C, unstable unless 30% glycerol is added
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Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
nickel chelating Sepharose column chromatography and S200 16/60 gel filtration
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recombinant enzyme
through Ni2+ affinity column chromatography, followed by a Hi-Load Superdex S-75 26/60 column chromatography
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using immobilized metal affinity chromatography, removal of N-terminal His tag, further purification by immobilized metal affinity chromatography and gel filtration using a Superdex 200 column
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Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expressed in Escherichia coli BL21(DE3) cells
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expression in Escherichia coli
insertion of the full length Sp2771 gene into pET28b vector with an N-terminal His-6 tag and expression in Escherichia coli (BL21/DE3) strain
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N-terminal His-tagged SySSADH expressed in Escherichia coli B834 (DE3) methionine auxotroph cells
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
decrease by growth of cells on gamma-aminobutanoate
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induction by growth on glutamate
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induction is highly coordinated with putrescine:2-oxoglutarate transaminase, gamma-aminobutyraldehyde dehydrogenase and gamma-aminobutyrate:2-oxoglutarate transaminase activities
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the expression of gabD is not specifically induced by either 4-hydroxybutanoic acid or gamma-aminobutanoate
the genes gabT, coding for glutamate:succinic semialdehyde transaminase, and gabD, encoding succinic semialdehyde dehydrogenase, are cotranscribed from a promoter located upstream of gabD
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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
E228Q
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active site mutation, nonfunctional because Glu-228 acts as a general base
F132A
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activity of about 1030% of the wild type enzyme, indicating a contribution of these succinic semialdehyde binding residues to the overall enzyme activity
F425A
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inactive, suggesting that Phe-425 plays an important role in substrate binding
I263A
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activity of about 1030% of the wild type enzyme, indicating a contribution of these succinic semialdehyde binding residues to the overall enzyme activity
N131A
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mutation of a residue that interacts with the O4 atom or the carboxyl group of succinic semialdehyde thus abolishing enzyme activity
N131D
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mutation of a residue that interacts with the O4 atom or the carboxyl group of succinic semialdehyde thus abolishing enzyme activity
R139K
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mutant enzyme exhibited an activity up to 80% that of the wild type enzyme, suggesting the significance of a positively charged residue in the binding of the carboxyl group of succinic semialdehyde
S157E
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mutation changes cofactor preference from NADP+ to NAD+, but enzyme activity is approximately 10fold reduced
W135A
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activity of about 1030% of the wild type enzyme, indicating a contribution of these succinic semialdehyde binding residues to the overall enzyme activity
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine
analysis of Escherichia coli SSADH structure with respect to human disease-linked mutations
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