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Information on EC 1.2.1.79 - succinate-semialdehyde dehydrogenase (NADP+)
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1.2.1.79 succinate-semialdehyde dehydrogenase (NADP+)IUBMB Comments
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+ .
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Word Map
- 1.2.1.79
- ssadhs
- nad+
- dehydrogenases
-
tricarboxylic
- cyanobacterium
- 2-oxoglutarate
- adduct
-
moss
- tca
-
syntrichia
-
shunt
- synechococcus
- medicine
The expected taxonomic range for this enzyme is: Bacteria, Archaea, Eukaryota
Synonyms
gabD, GabD1, NADP+-dependent succinic semialdehyde dehydrogenase, Sp2771, SpSSADH, SSADH, SSADH-II, SSO1842, succinic semialdehy de dehydrogenase, succinic semialdehyde dehydrogenase, 
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
gabD
GabD1
NADP+-dependent succinic semialdehyde dehydrogenase
Sp2771
SpSSADH
SSADH
SSADH-II
SSO1842
succinic semialdehyde dehydrogenase
SySSADH
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
succinate semialdehyde + NADP+ + H2O = succinate + NADPH + 2 H+
-
-
-
-
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PATHWAY SOURCE
PATHWAYS
KEGG
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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].
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
3-carboxybenzaldehyde + NADP+ + H2O
3-carboxybenzoate + NADPH + 2 H+
-
-
-
?
3-nitrobenzaldehyde + NADP+ + H2O
3-nitrobenzoate + NADPH + 2 H+
-
-
-
?
4-carboxybenzaldehyde + NADP+ + H2O
4-carboxybenzoate + NADPH + H+
-
-
-
?
malonate semialdehyde + NADP+ + H2O
malonate + NADPH + 2 H+
-
8.7% of the activity with succinate semialdehyde
-
-
?
succinate semialdehyde + NAD+ + H2O
succinate + NADH + 2 H+
about 11% of the activity with NADP+
-
-
?
succinate semialdehyde + NAD+ + H2O
succinate + NADH + 2 H+
kcat/Km for NADP+ is 250fold higher compared to kcat/Km for NAD+
-
-
?
succinate semialdehyde + NAD+ + H2O
succinate + NADH + 2 H+
kcat/Km for NADP+ is 250fold higher compared to kcat/Km for NAD+
-
-
?
succinate semialdehyde + NAD+ + H2O
succinate + NADH + 2 H+
-
-
-
?
succinate semialdehyde + NAD+ + H2O
succinate + NADH + 2 H+
-
-
-
?
succinate semialdehyde + NAD+ + H2O
succinate + NADH + H+
the enzyme activity in the presence of NADP+ is approximately 20fold higher than that measured in the presence of NAD+
-
-
?
succinate semialdehyde + NAD+ + H2O
succinate + NADH + H+
the enzyme activity in the presence of NADP+ is approximately 20fold higher than that measured in the presence of NAD+
-
-
?
succinate semialdehyde + NADP+ + H2O
succinate + NADPH + 2 H+
-
-
-
?
succinate semialdehyde + NADP+ + H2O
succinate + NADPH + 2 H+
-
-
-
?
succinate semialdehyde + NADP+ + H2O
succinate + NADPH + 2 H+
-
-
-
-
?
succinate semialdehyde + NADP+ + H2O
succinate + NADPH + 2 H+
-
-
-
?
succinate semialdehyde + NADP+ + H2O
succinate + NADPH + 2 H+
-
-
-
-
?
succinate semialdehyde + NADP+ + H2O
succinate + NADPH + 2 H+
kcat/Km for NADP+ is 250fold higher compared to kcat/Km for NAD+
-
-
?
succinate semialdehyde + NADP+ + H2O
succinate + NADPH + 2 H+
kcat/Km for NADP+ is 250fold higher compared to kcat/Km for NAD+
-
-
?
succinate semialdehyde + NADP+ + H2O
succinate + NADPH + 2 H+
-
-
-
?
succinate semialdehyde + NADP+ + H2O
succinate + NADPH + 2 H+
-
-
-
?
succinate semialdehyde + NADP+ + H2O
succinate + NADPH + 2 H+
-
-
-
?
succinate semialdehyde + NADP+ + H2O
succinate + NADPH + 2 H+
-
-
-
?
succinate semialdehyde + NADP+ + H2O
succinate + NADPH + 2 H+
-
-
-
r
succinate semialdehyde + NADP+ + H2O
succinate + NADPH + 2 H+
data from crystal structures provide details about the catalytic mechanism by revealing a covalent adduct of a cofactor with the catalytic cysteine in the binary complex and a proposed thiohemiacetal intermediate in the ternary complex
-
-
?
succinate semialdehyde + NADP+ + H2O
succinate + NADPH + 2 H+
binding structure, overview
-
-
r
succinate semialdehyde + NADP+ + H2O
succinate + NADPH + 2 H+
-
-
-
r
succinate semialdehyde + NADP+ + H2O
succinate + NADPH + 2 H+
binding structure, overview
-
-
r
succinate semialdehyde + NADP+ + H2O
succinate + NADPH + 2 H+
-
-
-
?
succinate semialdehyde + NADP+ + H2O
succinate + NADPH + H+
the enzyme activity in the presence of NADP+ is approximately 20fold higher than that measured in the presence of NAD+
-
-
?
succinate semialdehyde + NADP+ + H2O
succinate + NADPH + H+
the enzyme activity in the presence of NADP+ is approximately 20fold higher than that measured in the presence of NAD+
-
-
?
succinic semialdehyde + NADP+ + H2O
succinate + NADPH + 2 H+
chemical mechanism based on functional data and structural information proposed, 1H-NMR to probe the stereospecificity of GabD1 show a transfer of the deuteride to the pro-R position of NADP+ indicating GabD1 has A-type stereospecificity
-
-
ir
succinic semialdehyde + NADP+ + H2O
succinate + NADPH + 2 H+
chemical mechanism based on functional data and structural information proposed, 1H-NMR to probe the stereospecificity of GabD1 show a transfer of the deuteride to the pro-R position of NADP+ indicating GabD1 has A-type stereospecificity
-
-
ir
additional information
?
-
only the aldehyde forms and not the gem-diol forms of the specific substrate succinic semialdehyde , of selected aldehyde substrates, and of the inhibitor 3-tolualdehyde bind to the enzyme
-
-
?
additional information
?
-
-
no substrate: n-butanal, formaldehyde, acetaldehyde, glyoxal, glyoxalate, propanal, glutaraldehyde, benzaldehyde, and anisaldehyde
-
-
?
additional information
?
-
-
no substrate: glyoxylic acid, formic acid, formaldehyde, acetaldehyde, glyoxal, furfural and acrolein
-
-
?
additional information
?
-
other aldehydes, such as formaldehyde, acetaldehyde and glutaraldehyde, are very poor substrates showing a narrow substrate specificity of GabD1
-
-
?
additional information
?
-
other aldehydes, such as formaldehyde, acetaldehyde and glutaraldehyde, are very poor substrates showing a narrow substrate specificity of GabD1
-
-
?
additional information
?
-
in the binary enzyme-succinate semialdehyde-complex of SpSSADH, the succinate semialdehyde shows a tightly bound bent form nearby the catalytic residues, which may be caused by reduction of the cavity volume for substrate binding, compared with other SSADHs. Structural comparison of the tertiary enzyme-succinate semialdehyde-NADP+-complex with a binary complex + of SpSSADH with NADP indicates that the substrate inhibition is induced by the binding of inhibitory succinate semialdehyde in the cofactor-binding site, instead of NADP+. In the active site of enzyme SpSSADH, SSA is buried inside of the substrate-binding pocket formed by Phe133, Tyr136, Val262, Trp418 and Phe426 residues, substrate binding structure, overview
-
-
?
additional information
?
-
in the binary enzyme-succinate semialdehyde-complex of SpSSADH, the succinate semialdehyde shows a tightly bound bent form nearby the catalytic residues, which may be caused by reduction of the cavity volume for substrate binding, compared with other SSADHs. Structural comparison of the tertiary enzyme-succinate semialdehyde-NADP+-complex with a binary complex + of SpSSADH with NADP indicates that the substrate inhibition is induced by the binding of inhibitory succinate semialdehyde in the cofactor-binding site, instead of NADP+. In the active site of enzyme SpSSADH, SSA is buried inside of the substrate-binding pocket formed by Phe133, Tyr136, Val262, Trp418 and Phe426 residues, substrate binding structure, overview
-
-
?
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NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
succinate semialdehyde + NAD+ + H2O
succinate + NADH + H+
the enzyme activity in the presence of NADP+ is approximately 20fold higher than that measured in the presence of NAD+
-
-
?
succinate semialdehyde + NAD+ + H2O
succinate + NADH + H+
the enzyme activity in the presence of NADP+ is approximately 20fold higher than that measured in the presence of NAD+
-
-
?
succinate semialdehyde + NADP+ + H2O
succinate + NADPH + 2 H+
-
-
-
?
succinate semialdehyde + NADP+ + H2O
succinate + NADPH + 2 H+
-
-
-
?
succinate semialdehyde + NADP+ + H2O
succinate + NADPH + 2 H+
-
-
-
?
succinate semialdehyde + NADP+ + H2O
succinate + NADPH + 2 H+
-
-
-
r
succinate semialdehyde + NADP+ + H2O
succinate + NADPH + 2 H+
data from crystal structures provide details about the catalytic mechanism by revealing a covalent adduct of a cofactor with the catalytic cysteine in the binary complex and a proposed thiohemiacetal intermediate in the ternary complex
-
-
?
succinate semialdehyde + NADP+ + H2O
succinate + NADPH + 2 H+
-
-
-
r
succinate semialdehyde + NADP+ + H2O
succinate + NADPH + 2 H+
-
-
-
?
succinate semialdehyde + NADP+ + H2O
succinate + NADPH + H+
the enzyme activity in the presence of NADP+ is approximately 20fold higher than that measured in the presence of NAD+
-
-
?
succinate semialdehyde + NADP+ + H2O
succinate + NADPH + H+
the enzyme activity in the presence of NADP+ is approximately 20fold higher than that measured in the presence of NAD+
-
-
?
succinic semialdehyde + NADP+ + H2O
succinate + NADPH + 2 H+
chemical mechanism based on functional data and structural information proposed, 1H-NMR to probe the stereospecificity of GabD1 show a transfer of the deuteride to the pro-R position of NADP+ indicating GabD1 has A-type stereospecificity
-
-
ir
succinic semialdehyde + NADP+ + H2O
succinate + NADPH + 2 H+
chemical mechanism based on functional data and structural information proposed, 1H-NMR to probe the stereospecificity of GabD1 show a transfer of the deuteride to the pro-R position of NADP+ indicating GabD1 has A-type stereospecificity
-
-
ir
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
NAD+
NAD+ acts as cosubstrate, but the reaction rates are more than 20fold lower than those with NADP+
NAD+
the enzyme activity in the presence of NADP+ is approximately 20fold higher than that measured in the presence of NAD+
NAD+
kcat/Km for NADP+ is 250fold higher compared to kcat/Km for NAD+
NADP+
electron density analysis of binding site. The enzyme activity measured in the presence of NADP+ is approximately 20fold higher than that measured in the presence of NAD+
NADP+
NAD+ also acts as cosubstrate, but the reaction rates are more than 20fold lower than those with NADP+
NADP+
the enzyme activity in the presence of NADP+ is approximately 20fold higher than that measured in the presence of NAD+
NADP+
kcat/Km for NADP+ is 250fold higher compared to kcat/Km for NAD+
NADP+
enzyme activity increases significantly, and the enzyme becomes resistant to oxidative stress in presence of NADP+ and DTT
NADP+
Ser157 residue in Sp2771 plays a critical structural role in determining NADP+ preference for Sp2771, whereas size and distribution of hydrophobic residues along the substrate binding funnel determine substrate selection
additional information
no detectable activity by using NAD+ as cofactor
-
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
3-tolualdehyde
only the aldehyde forms and not the gem-diol forms of the inhibitor 3-tolualdehyde bind to the enzyme
H2O2
50 microM H2O2 sharply reduces activity to 31% of the H2O2-free enzyme and activity further decreases to 3% at 1 mM H2O2
Succinic semialdehyde
partial substrate inhibition because velocity decreases to a non-zero value at saturating concentrations of Mg2+ and succinic semialdehyde
succinate semialdehyde
uncompetitive substrate inhibition above 0.02 mM, in the presence of NADP+. Substrate inhibition is induced by the binding of inhibitory succinate semialdehyde in the cofactor-binding site, instead of NADP+
succinate semialdehyde
complete uncompetitive substrate inhibition. Structural comparison of the tertiary enzyme-succinate semialdehyde-NADP+-complex with a binary complex of SpSSADH with NADP indicates that the substrate inhibition is induced by the binding of inhibitory succinate semialdehyde in the cofactor-binding site, instead of NADP+
additional information
analysis of the kinetic inhibitory parameters revealed significant substrate inhibition in the presence of NADP+ at concentrations of succinate semialdehyde higher than 0.02 mM, which exhibits complete uncompetitive substrate inhibition, structure-based molecular insights into the substrate inhibition mechanism of SpSSADH, overview
-
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
DTT
enzyme activity increases significantly, and the enzyme becomes resistant to oxidative stress in presence of NADP+ and DTT
2-mercaptoethanol
-
loss of about 80% of original acitivity after exhaustive dialysis, renaturation in presence of 2-mercaptoethanol
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0092
NADP+
steady-state parameter, 50 microM NADP+ and 10 mM Mg2+, at pH 7.5 and 37°C
0.0613
NADP+
steady-state parameter, 50 microM NADP+, at pH 7.5 and 37°C
0.00395
succinate semialdehyde
recombinant enzyme, pH 7.0, 30°C
0.01694
succinate semialdehyde
in 100 mM sodium phosphate buffer, pH 8.0, 30°C
0.003
Succinic semialdehyde
steady-state parameter, 200 microM succinic semialdehyde and 10 mM Mg2+, at pH 7.5 and 37°C
0.0133
Succinic semialdehyde
steady-state parameter, 200 microM succinic semialdehyde, at pH 7.5 and 37°C
additional information
additional information
Michaelis-Menten kinetics
-
additional information
additional information
enzyme does not obey Michaelis-Menten kinetics
-
additional information
additional information
the Km-value of succinate semialdehyde estimated to be far less than 0.05 mM
-
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
1.3
NADP+
steady-state parameter, 50 microM NADP+, at pH 7.5 and 37°C
2.7
NADP+
steady-state parameter, 50 microM NADP+ and 10 mM Mg2+, at pH 7.5 and 37°C
1.69
succinate semialdehyde
recombinant enzyme, pH 7.0, 30°C
1.9
Succinic semialdehyde
steady-state parameter, 200 microM succinic semialdehyde, at pH 7.5 and 37°C
4.7
Succinic semialdehyde
steady-state parameter, 200 microM succinic semialdehyde and 10 mM Mg2+, at pH 7.5 and 37°C
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kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
21
NADP+
steady-state parameter, 50 microM NADP+, at pH 7.5 and 37°C
290
NADP+
steady-state parameter, 50 microM NADP+ and 10 mM Mg2+, at pH 7.5 and 37°C
426
succinate semialdehyde
recombinant enzyme, pH 7.0, 30°C
140
Succinic semialdehyde
steady-state parameter, 200 microM succinic semialdehyde, at pH 7.5 and 37°C
1600
Succinic semialdehyde
steady-state parameter, 200 microM succinic semialdehyde and 10 mM Mg2+, at pH 7.5 and 37°C
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Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0628
Succinic semialdehyde
partial substrate inhibition, pH 7.5 and 37°C
0.1
succinate semialdehyde
recombinant enzyme, pH 7.0, 30°C
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IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
5.5 - 10
GabD1 could not be assayed below pH 5.5, due to precipitation and loss of activity
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
22
30
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
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LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
metabolism
physiological function
additional information
evolution
SSADH belongs to the aldehyde dehydrogenase (ALDH) superfamily
evolution
-
SSADH belongs to the aldehyde dehydrogenase (ALDH) superfamily
-
metabolism
SSADH plays an essential role in the metabolism of the inhibitory neurotransmitter c-aminobutyric acid
metabolism
enzyme catalyzes the last step of the gamma-aminobutyrate degradation
metabolism
Sp2771 enzyme completes together with a novel 2-oxoglutarate decarboxylase a non-canonical tricarboxylic acid cycle
metabolism
succinic semialdehyde dehydrogenase from Synechococcus is an essential enzyme in the tricarboxylic acid cycle of cyanobacteria
metabolism
-
enzyme catalyzes the last step of the gamma-aminobutyrate degradation
-
metabolism
-
SSADH plays an essential role in the metabolism of the inhibitory neurotransmitter c-aminobutyric acid
-
physiological function
gene is disrupted in a transposon-induced mutant of Ralstonia eutropha exhibiting the phenotype 4-hydroxybutyric acid-leaky
physiological function
succinic semialdehyde dehydrogenase from Synechococcus is an essential enzyme in the tricarboxylic acid, TCA, cycle of cyanobacteria. It completes a 2-oxoglutarate dehydrogenase-deficient cyanobacterial TCA cycle through a detour metabolic pathway. SySSADH produces succinate in an NADP+ -dependent manner with a single cysteine acting as the catalytic residue in the catalytic loop
physiological function
-
succinic semialdehyde dehydrogenase from Synechococcus is an essential enzyme in the tricarboxylic acid, TCA, cycle of cyanobacteria. It completes a 2-oxoglutarate dehydrogenase-deficient cyanobacterial TCA cycle through a detour metabolic pathway. SySSADH produces succinate in an NADP+ -dependent manner with a single cysteine acting as the catalytic residue in the catalytic loop
-
additional information
Ser157 residue in Sp2771 plays a critical structural role in determining NADP+ preference for Sp2771, whereas size and distribution of hydrophobic residues along the substrate binding funnel determine substrate selection. Enzyme Sp2771 structure modelling comprising residues 2-454, active site and substrate binding structures, overview
additional information
structure analysis of the enzyme in binary and ternary with NADP(H) and/or substrate reveals that the enzyme forms a distinct reaction intermediate in each complex: a covalent adduct of a cofactor with the catalytic cysteine in the binary complex and a proposed thiohemiacetal intermediate in the ternary complex. SySSADH produces succinate in an NADP+ -dependent manner with a single cysteine acting as the catalytic residue in the catalytic loop, catalytic mechanism, overview. The formation of the NADP-cysteine adduct is a kinetically preferred event that protects the catalytic cysteine from H2O2-dependent oxidative stress. SySSADH shows a cofactor-dependent oxidation protection in 1-Cys SSADH, which is unique relative to other 2-Cys SSADHs employing a redox-dependent formation of a disulfide bridge. The catalytic cysteine preferentially forms an NADP-cysteine adduct if NADP+ is present
additional information
-
structure analysis of the enzyme in binary and ternary with NADP(H) and/or substrate reveals that the enzyme forms a distinct reaction intermediate in each complex: a covalent adduct of a cofactor with the catalytic cysteine in the binary complex and a proposed thiohemiacetal intermediate in the ternary complex. SySSADH produces succinate in an NADP+ -dependent manner with a single cysteine acting as the catalytic residue in the catalytic loop, catalytic mechanism, overview. The formation of the NADP-cysteine adduct is a kinetically preferred event that protects the catalytic cysteine from H2O2-dependent oxidative stress. SySSADH shows a cofactor-dependent oxidation protection in 1-Cys SSADH, which is unique relative to other 2-Cys SSADHs employing a redox-dependent formation of a disulfide bridge. The catalytic cysteine preferentially forms an NADP-cysteine adduct if NADP+ is present
-
Show AA Sequence and Transmembrane Helices (4344 entries)
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PDB
SCOP
CATH
UNIPROT
ORGANISM
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MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
Sp2771 monomer is composed of N-terminal cofactor binding domain, a catalytic domain and an oligomerization domain
homodimer
tetramer
additional information
the central parts of both cofactor binding domain and catalytic domain contain atypical alpha/beta structure. The catalytic domain consists of a seven stranded beta-sheet flanked by two alpha-helices on one side and three alpha-helices on the other side.The cofactor binding domain displays the two tandem Rossmann folds for NADP+ binding . The oligomerization domain contains three-stranded antiparallel beta-sheets protruding across the center of the dimer interface, while the NADP+ binding site is on the opposite side of the dimer interface
homodimer
gel filtration, SySSADH monomer consists of three segments - alpha/beta-fold N- and C-domains for a cofactor binding and a catalytic domain, and three antiparallel beta-strands constituting a dimerization domain
homodimer
the overall structure of monomeric SySSADH is reminiscent of an ALDH fold. It is made up of three segments: alpha/beta-fold N- and C-domains for a cofactor binding and a catalytic domain, respectively, and three antiparallel beta-strands constituting a dimerization domain
homodimer
-
the overall structure of monomeric SySSADH is reminiscent of an ALDH fold. It is made up of three segments: alpha/beta-fold N- and C-domains for a cofactor binding and a catalytic domain, respectively, and three antiparallel beta-strands constituting a dimerization domain
-
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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)
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 1â125, 148â256, and 457â472, a catalytic domain of residues 257â456, and an oligomerization domain of residues 126â147 and 473â482. 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 beta15âbeta16 causes the formation of a water molecule-mediated hydrogen bond network between the connecting loop and the catalytic loop in Escherichia coli SSADH
-
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
enzyme SpSSADH in a binary complex with succinate semialdehyde as the substrate and a ternary complex with succinate semialdehyde and NADP+, hanging-drop vapor diffusion method, mixing of mixture of 0.001 ml of protein solution with 0.001 ml of reservoir solution, for the binary complex crystal, SpSSADH is pre-incubated with succinate semialdehyde at the molar ratio of 1:2, and the protein-substrate mixture is crystallized over 00.5 ml of reservoir solution containing 0.1 M sodium acetate trihydrate, pH 4.6, and 2.0 M ammonium sulfate, the trinary complex is obtained by soaking the pre-grown NADP+ co-crystallized crystal with a 1:10 molar ratio of succinate semialdehyde under the same reservoir conditions, 22°C, X-ray diffraction structure determination and analysis at 2.4 A resolution, molecular replacement method with the apo-structure of SpSSADH, PDB ID 4OGD, as the search model
structures in a binary complex with succinic semialdehyde as the substrate and a ternary complex with the substrate succinic semialdehyde and the inhibitory succinate semialdehyde, at 2.4 A resolution for both structures
structures in apo-form and in a binary complex with NADP+ at 1.6 A and 2.1 A resolutions, respectively. Both structures show dimeric conformation and contain a single cysteine residue in the catalytic loop of each subunit. Residues Ser158 and Tyr188 participate in the stabilization of the 2'-phosphate group of adenine-side ribose in NADP+
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
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
purified recombinant enzyme in apo form, in a binary complex with NADP+, and in a ternary complex with succinic semialdehyde and NADPH, sitting drop vapor diffusion method, using a crystallization buffer of 0.05 M potassium phosphate monobasic, 20% w/v PEG 8000, and 2 mM CaCl2, 22°C, for the binary and tertiary complexes, a pre-grown crystals of SySSADH are soaked for 60 min in a solution of 0.05 M potassium phosphate monobasic, 20% w/v PEG8000, 30% v/v ethylene glycol, and 50 mM NADPH or 50 mM NADPH and 50 mM succinate semialdehyde, respectively, X-ray diffraction structure determination and analysis at 1.4-1.7 A resolution, single-wavelength diffraction, modelling
purified recombinant His6-tagged wild-type Sp2771, and Sp2771 S419A and Sp2771 C262A mutants in ternary complex with NADP+ and succinate semialdehyde, mixing of 0.001 ml of protein solution and reservoir solution each, the latter containing 15% PEG 5000 MME , 1 mM DTT, 3% tascimate, and 100 mM HEPES, pH 6.8 for the wild-type enzyme and the mutants, for Sp2771 mutants in complex with NADP+ and succinate semialdehyde, NAD+ and succinate semialdehyde are incubated with proteins for 15 min at room temperature before crystallization, 20°C, 3 days, X-ray diffraction structure determination and analysis at 1.7-2.5 A resolution, molecular replacement using Escherichia coli SSADH structure, PDB ID 3JZ4, as search model
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
C262A
E228A
E228Q
active site mutation, nonfunctional because Glu-228 acts as a general base
F132A
activity of about 10â30% of the wild type enzyme, indicating a contribution of these succinic semialdehyde binding residues to the overall enzyme activity
F425A
inactive, suggesting that Phe-425 plays an important role in substrate binding
I263A
activity of about 10â30% of the wild type enzyme, indicating a contribution of these succinic semialdehyde binding residues to the overall enzyme activity
N131A
mutation of a residue that interacts with the O4 atom or the carboxyl group of succinic semialdehyde thus abolishing enzyme activity
N131D
mutation of a residue that interacts with the O4 atom or the carboxyl group of succinic semialdehyde thus abolishing enzyme activity
R139A
R139K
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
mutation changes cofactor preference from NADP+ to NAD+, but enzyme activity is approximately 10fold reduced
S419A
W135A
activity of about 10â30% of the wild type enzyme, indicating a contribution of these succinic semialdehyde binding residues to the overall enzyme activity
C262A
site-directed mutagenesis, Sp2771 mutant structure analysis and comparison to the wild-type structure
S419A
site-directed mutagenesis, Sp2771 mutant structure analysis and comparison to the wild-type structure
C262A
active site mutation, nonfunctional because Cys-262 acts as a nucleophilel
E228A
active site mutation, nonfunctional because Glu-228 acts as a general base
R139A
90% reduced catalytic activity, residue is involved in substrate binding
R139A
activity of about 10â30% of the wild type enzyme, indicating a contribution of these succinic semialdehyde binding residues to the overall enzyme activity
S419A
80% reduced catalytic activity, residue is involved in substrate binding
S419A
mutation of a residue that interacts with the O4 atom or the carboxyl group of succinic semialdehyde thus abolishing enzyme activity
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pH STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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OXIDATION STABILITY
ORGANISM
UNIPROT
LITERATURE
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
725523
SySSADH is an oxidation-sensitive enzyme, the formation of the NADP-cysteine adduct is a kinetically preferred event that protects the catalytic cysteine from H2O2-dependent oxidative stress. Over 70% of the original SySSADH activity is maintained with 0.005-0.25 mM H2O2 with a further drop of activity to 40% at 1 m H2O2. Comparable or even higher enzyme activity is observed when SySSADH is preincubated for 10 min with 2.5 mM NADP+ followed by H2O2 treatment for 60 min
742844
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STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
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PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
nickel chelating Sepharose column chromatography and S200 16/60 gel filtration
recombinant His6-tagged wild-type and mutant enzymes from Escherichia coli strain BL21(DE3) by nickel affinity chromatography, gel filtration, and ultrafiltration
recombinant N-terminally His-tagged SySSADH from Escherichia coli strain B834(DE3) by nickel affinity chromatography, dialysis and cleavge fo the His-tag by tobacco etch mosaic virus protease, followed by another step of immobilized metal affinity chromatography and gel filtration. Recombinant His-tagged enzyme mutants from Escherichia coli strain coli BL21(DE3) by immobilized metal affinity chromatography and dialysis
through Ni2+ affinity column chromatography, followed by a Hi-Load Superdex S-75 26/60 column chromatography
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
expression in Escherichia coli
gene ssadh, recombinant expression in Escherichia coli strain BL21(DE3)
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
N-terminal His-tagged SySSADH expressed in Escherichia coli B834 (DE3) methionine auxotroph cells
recombinant expression of His6-tagged wild-type and mutant enzymes in Escherichia coli strain BL21/DE3
recombinant expression of N-terminally His-tagged SySSADH (residues Met1 to Lys454) in Escherichia coli methionine-auxotrophic strain B834(DE3), recombinant expression of His-tagged enzyme mutants in Escherichia coli strain coli BL21(DE3). Juxtaposition of the N- and C-domains generates an active site tunnel between the two domains that is accessible from both ends. The catalytic residues are located in the middle of the tunnel. A nucleophile Cys262 is located in the catalytic loop between alphaa8 and beta11 of the C-domain, and a general base Glu228 is located in an interdomain-connecting loop between beta9 and beta10. Dimerization is mediated largely by N-domain alpha7 and the three antiparallel beta-strands (beta3, beta4, beta17) protruding from the N- and C-domains
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
induction is highly coordinated with putrescine:2-oxoglutarate transaminase, gamma-aminobutyraldehyde dehydrogenase and gamma-aminobutyrate:2-oxoglutarate transaminase activities
-
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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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
analysis of Escherichia coli SSADH structure with respect to human disease-linked mutations
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REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Sanchez, M.; Fernandez, J.; Martin, M.; Gibello, A.; Garrido-Pertierra, A.
Purification and properties of two succinic semialdehyde dehydrogenases from Klebsiella pneumoniae
Biochim. Biophys. Acta
990
225-231
1989
Klebsiella pneumoniae
brenda
Tokunaga, M.; Nakano, Y.; Kitaoka, S.
Separation and properties of the NAD-linked and NADP-linked isozymes of succinic semialdehyde dehydrogenase in Euglena gracilis z
Biochim. Biophys. Acta
429
55-62
1976
Euglena gracilis
brenda
Lutke-Eversloh, T.; Steinbuchel, A.
Biochemical and molecular characterization of a succinate semialdehyde dehydrogenase involved in the catabolism of 4-hydroxybutyric acid in Ralstonia eutropha
FEMS Microbiol. Lett.
181
63-71
1999
Cupriavidus necator (Q9RBF6)
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Jaeger, M.; Rothacker, B.; Ilg, T.
Saturation transfer difference NMR studies on substrates and inhibitors of succinic semialdehyde dehydrogenases
Biochem. Biophys. Res. Commun.
372
400-406
2008
Escherichia coli (P25526)
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Ahn, J.-W.; Kim, Y.-G.; Kim, K.-J.
Crystal structure of non-redox regulated SSADH from Escherichia coli
Biochem. Biophys. Res. Commun.
392
106-111
2010
Escherichia coli
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Cozzani, I.; Fazio, A.M.; Felici, E.; Barletta, G.
Separation and characterization of NAD- and NADP-specific succinate-semialdehyde dehydrogenase from Escherichia coli K-12 3300
Biochim. Biophys. Acta
613
309-317
1980
Escherichia coli K-12
brenda
Sanchez, M.; Alvarez, M.A.; Balana, R.; Garrido-Pertierra, A.
Properties and functions of two succinic-semialdehyde dehydrogenases from Pseudomonas putida
Biochim. Biophys. Acta
953
249-257
1988
Pseudomonas putida
brenda
Bartsch, K.; von Johnn-Marteville, A.; Schulz, A.
Molecular analysis of two genes of the Escherichia coli gab cluster: nucleotide sequence of the glutamate:succinic semialdehyde transaminase gene (gabT) and characterization of the succinic semialdehyde dehydrogenase gene (gabD)
J. Bacteriol.
172
7035-7042
1990
Escherichia coli
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Langendorf, C.G.; Key, T.L.; Fenalti, G.; Kan, W.T.; Buckle, A.M.; Caradoc-Davies, T.; Tuck, K.L.; Law, R.H.; Whisstock, J.C.
The X-ray crystal structure of Escherichia coli succinic semialdehyde dehydrogenase; structural insights into NADP+/enzyme interactions
PLoS One
5
e9280
2010
Escherichia coli (P25526), Escherichia coli K-12 (P25526), Escherichia coli MC1061 (P25526)
brenda
Esser, D.; Kouril, T.; Talfournier, F.; Polkowska, J.; Schrader, T.; Bräsen, C.; Siebers, B.
Unraveling the function of paralogs of the aldehyde dehydrogenase super family from Sulfolobus solfataricus
Extremophiles
17
205-216
2013
Saccharolobus solfataricus (Q97XA5), Saccharolobus solfataricus P2 (Q97XA5)
brenda
de Carvalho, L.P.; Ling, Y.; Shen, C.; Warren, J.D.; Rhee, K.Y.
On the chemical mechanism of succinic semialdehyde dehydrogenase (GabD1) from Mycobacterium tuberculosis
Arch. Biochem. Biophys.
509
90-99
2011
Mycobacterium tuberculosis (P9WNX9), Mycobacterium tuberculosis H37Rv (P9WNX9)
brenda
Park, J.; Rhee, S.
Structural basis for a cofactor-dependent oxidation protection and catalysis of cyanobacterial succinic semialdehyde dehydrogenase
J. Biol. Chem.
288
15760-15770
2013
Synechococcus sp. (B1XMM6)
brenda
Yuan, Z.; Yin, B.; Wei, D.; Yuan, Y.R.
Structural basis for cofactor and substrate selection by cyanobacterium succinic semialdehyde dehydrogenase
J. Struct. Biol.
182
125-135
2013
Synechococcus sp. (B1XMM6)
brenda
Jang, E.H.; Park, S.A.; Chi, Y.M.; Lee, K.S.
Structural insight into the substrate inhibition mechanism of NADP(+)-dependent succinic semialdehyde dehydrogenase from Streptococcus pyogenes
Biochem. Biophys. Res. Commun.
461
487-493
2015
Streptococcus pyogenes (A0A0J9X1M8), Streptococcus pyogenes MGAS1882 (A0A0J9X1M8)
brenda
Jang, E.H.; Park, S.A.; Chi, Y.M.; Lee, K.S.
Kinetic and structural characterization for cofactor preference of succinic semialdehyde dehydrogenase from Streptococcus pyogenes
Mol. Cells
37
719-726
2014
Streptococcus pyogenes (A0A0J9X1M8), Streptococcus pyogenes MGAS1882 (A0A0J9X1M8)
brenda
Jang, E.H.; Park, S.A.; Chi, Y.M.; Lee, K.S.
Structural insight into the substrate inhibition mechanism of NADP+-dependent succinic semialdehyde dehydrogenase from Streptococcus pyogenes
Biochem. Biophys. Res. Commun.
461
487-493
2015
Streptococcus pyogenes (A0A0J9X1M8), Streptococcus pyogenes MG-AS1882 (A0A0J9X1M8)
brenda
Park, J.; Rhee, S.
Structural basis for a cofactor-dependent oxidation protection and catalysis of cyanobacterial succinic semialdehyde dehydrogenase
J. Biol. Chem.
288
15760-15770
2013
Synechococcus sp. (B1XMM6), Synechococcus sp. ATCC 27264 (B1XMM6)
brenda
Yuan, Z.; Yin, B.; Wei, D.; Yuan, Y.R.
Structural basis for cofactor and substrate selection by cyanobacterium succinic semialdehyde dehydrogenase
J. Struct. Biol.
182
125-135
2013
Synechococcus sp. PCC 7002 (B1XMM6)
brenda
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