1.2.1.79: succinate-semialdehyde dehydrogenase (NADP+)
This is an abbreviated version!
For detailed information about succinate-semialdehyde dehydrogenase (NADP+), go to the full flat file.
Word Map on EC 1.2.1.79
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1.2.1.79
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ssadhs
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nad+
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dehydrogenases
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tricarboxylic
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cyanobacterium
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2-oxoglutarate
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adduct
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moss
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tca
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syntrichia
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shunt
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synechococcus
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medicine
- 1.2.1.79
- ssadhs
- nad+
- dehydrogenases
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tricarboxylic
- cyanobacterium
- 2-oxoglutarate
- adduct
-
moss
- tca
-
syntrichia
-
shunt
- synechococcus
- medicine
Reaction
Synonyms
AbSSADH, ALDH21, all3556, ApSSADH, gabD, GabD1, NADP+-dependent SSADH, NADP+-dependent succinic semialdehyde dehydrogenase, NADP-dependent succinic semialdehyde dehydrogenase, PpSSALDH, slr0370, Sp2771, SpSSADH, SSADH, SSADH-II, SSALDH, SSO1842, succinic semialdehy de dehydrogenase, succinic semialdehyde dehydrogenase, SYNPCC7002_A2771, SySSADH
ECTree
1.2.1.79 succinate-semialdehyde dehydrogenase (NADP+)Advanced search results
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General Information on EC 1.2.1.79 - succinate-semialdehyde dehydrogenase (NADP+)
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GENERAL INFORMATION 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
evolution
malfunction
both R121A and R457A variants are almost inactive, demonstrating a key role of each arginine in catalysis
metabolism
physiological function
additional information
evolution
SSADH belongs to the aldehyde dehydrogenase (ALDH) superfamily
evolution
sequence analysis of AbSSADH reveals its high degree of sequence similarity to other enzymes in the two-cysteine GabD family
evolution
SSADH belongs to the aldehyde dehydrogenase (ALDH) superfamily, which is a kind of NAD(P)+-dependent oxidoreductase using a wide range of aldehydes as its substrate
evolution
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SSADH belongs to the aldehyde dehydrogenase (ALDH) superfamily
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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
SySSADH catalyzes one of the NAD(P)H generating reactions in the oxidative TCA cycle. The oxidative TCA cycle is a pathway with low efficiency in NADPH generation in Synechocystis sp. 6803. Similar to isocitrate dehydrogenase from Synechocystis sp. 6803, SySSADH specifically catalyzes the NADPH-generating reaction and is not inhibited by citrate. To avoid NADPH overproduction, the oxidative pentose phosphate (OPP) pathway dehydrogenase activity is repressed when the flow of the oxidative TCA cycle increases in Synechocystis sp. 6803. Metabolic map around the OPP pathway, overview
metabolism
the enzyme is involved in the GABA shunt pathway, GABA shunt reactions from glutamate to succinate might appear in cytosol in addition to mitochondria making the GABA shunt pathway much more diverse
metabolism
the ssadh gene from Acinetobacter baumannii is part of the 4-hydroxyphenylacetate (4-HPA) degradation pathway in which SSADH converts SSA to succinic acid before entering the main metabolic TCA cycle
metabolism
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enzyme catalyzes the last step of the gamma-aminobutyrate degradation
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metabolism
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SSADH plays an essential role in the metabolism of the inhibitory neurotransmitter c-aminobutyric acid
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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
ALDH21 from the moss Physcomitrella patens codes for a tetrameric NADP+-dependent succinic semialdehyde dehydrogenase (SSALDH), which converts succinate semialdehyde, an intermediate of the gamma-aminobutyric acid (GABA) shunt pathway, into succinate in the cytosol
physiological function
production of glutaric acid depends on the expression of native gabT (EC 2.6.1.48) and gabD of Corynebacterium glutamicum, or on heterologous expression of davT (EC 2.6.1.48) and davD (EC 1.2.1.20) from Pseudomonas putida encoding 5-aminovalerate aminotransferase, and glutarate semialdehyde, respectively
physiological function
succinic semialdehyde dehydrogenase (SSADH) from Synechocystis 6803 (SySSADH) catalyzes one of the NAD(P)H generating reactions in the oxidative TCA cycle. Similar to isocitrate dehydrogenase from Synechocystis sp. 6803, SySSADH specifically catalyzes the NADPH-generating reaction and is not inhibited by citrate. The activity of SySSADH is lower than that of other bacterial SSADHs
physiological function
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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
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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
AbSSADH contains a total of five cysteine residues in one subunit (Cys175, Cys245, Cys289, Cys291 and Cys479), the enzyme has two conserved cysteines, Cys289 and Cys291. Cys289 is the active residue participating in catalysis. Method devlopment to specifically measure the active site cysteine pKa without interference from other cysteines, overview. As the magnitude of burst kinetics represents the amount of NADPH formed during the first turnover, it is directly dependent on the amount of the deprotonated form of cysteine. The pKa of Cys289 was calculated from a plot of the burst magnitude vs. pH as 7.4. The Cys289 pKa is also measured based on the ability of AbSSADH to form an NADP-cysteine adduct, which can be detected by the increase of absorbance at about 330 nm as 7.9. The lowering of the catalytic cysteine pKa by 0.6-1.0 unit renders the catalytic thiol more nucleophilic, which facilitates AbSSADH catalysis under physiological conditions. Deprotonation of the ligand or an active site residue is required for the SSADH reaction
additional information
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AbSSADH contains a total of five cysteine residues in one subunit (Cys175, Cys245, Cys289, Cys291 and Cys479), the enzyme has two conserved cysteines, Cys289 and Cys291. Cys289 is the active residue participating in catalysis. Method devlopment to specifically measure the active site cysteine pKa without interference from other cysteines, overview. As the magnitude of burst kinetics represents the amount of NADPH formed during the first turnover, it is directly dependent on the amount of the deprotonated form of cysteine. The pKa of Cys289 was calculated from a plot of the burst magnitude vs. pH as 7.4. The Cys289 pKa is also measured based on the ability of AbSSADH to form an NADP-cysteine adduct, which can be detected by the increase of absorbance at about 330 nm as 7.9. The lowering of the catalytic cysteine pKa by 0.6-1.0 unit renders the catalytic thiol more nucleophilic, which facilitates AbSSADH catalysis under physiological conditions. Deprotonation of the ligand or an active site residue is required for the SSADH reaction
additional information
the catalytic active center harbors residues such as Cys262, Glu228, Asn131, Arg139 and Ser420. Structure homology modeling of ApSSADH based on the crystal structure of enzyme SpSSADH (PDB ID 3VZ3) from Synechocystis sp. PCC6803. The residues of Cys262 and Asn131 interact with the carbonyl oxygen atom of SSA through the backbone NH group via hydrogen bond. Meanwhile, the side chains of Ser420 and Arg139 interact with the carboxyl oxygen of SSA directly. In addition, the side chains of Arg139 and Glu228 residues interact with the amide group of NADP+
additional information
the crystal structure with the bound product succinate shows that its carboxylate group establishes salt bridges with both Arg121 and Arg457, and a hydrogen bond with Tyr296. While both arginine residues are pre-formed for substrate/product binding, Tyr296 moves by more than 1.0 A. Key role of R121 and R457 residues in catalysis. Structure-function analysis, overview
additional information
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the crystal structure with the bound product succinate shows that its carboxylate group establishes salt bridges with both Arg121 and Arg457, and a hydrogen bond with Tyr296. While both arginine residues are pre-formed for substrate/product binding, Tyr296 moves by more than 1.0 A. Key role of R121 and R457 residues in catalysis. Structure-function analysis, overview
additional information
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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
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