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L-cystine inhibits aspartate-beta-semialdehyde dehydrogenase by covalently binding to the essential 135Cys of the enzyme

Alvarez, E.; Ramon, F.; Magan, C.; Diez, E.; Biochim. Biophys. Acta 1696, 23-29 (2004)

Data extracted from this reference:

Inhibitors
EC Number
Inhibitors
Commentary
Organism
Structure
1.2.1.11
D-Cystine
70% inhibition at 0.01 mM, binds via the cysteine moiety covalently to the catalytic Cys135 of the enzyme, pH-dependent proces, optimal at pH 7.0-7.5, inhibition is reversible by DTT, dithioerythritol, 2-mercaptoethanol, dimercaptopropanol, and reduced glutathione, no protection by aspartate-beta-semialdehyde, NADP+ or NADPH, inhibition mechanism and kinetics
Escherichia coli
1.2.1.11
DTNB
reversible by DTT, dithioerythritol, 2-mercaptoethanol, dimercaptopropanol, and reduced glutathione
Escherichia coli
1.2.1.11
GSSG
oxidized glutathione
Escherichia coli
1.2.1.11
L-2-Amino-4-oxo-5-chloropentanoic acid
substrate analogue, irreversible inactivation, pseudo-first-order kinetics
Escherichia coli
1.2.1.11
L-cystine
complete inhibition at 0.01 mM, binds via the cysteine moiety covalently to the catalytic Cys135 of the enzyme, pH-dependent process, optimal at pH 7.0-7.5, inhibition is reversible by DTT, dithioerythritol, 2-mercaptoethanol, dimercaptopropanol, and reduced glutathione, no protection by aspartate-beta-semialdehyde, NADP+ or NADPH, inhibition mechanism and kinetics
Escherichia coli
1.2.1.11
L-cystine diethyl ester
68% inhibition at 0.01 mM, reversible by DTT, dithioerythritol, 2-mercaptoethanol, dimercaptopropanol, and reduced glutathione
Escherichia coli
1.2.1.11
L-cystine dimethyl ester
67% inhibition at 0.01 mM, reversible by DTT, dithioerythritol, 2-mercaptoethanol, dimercaptopropanol, and reduced glutathione
Escherichia coli
1.2.1.11
L-cystine hydroxamate
20% inhibition at 0.01 mM, reversible by DTT, dithioerythritol, 2-mercaptoethanol, dimercaptopropanol, and reduced glutathione
Escherichia coli
1.2.1.11
additional information
no inhibition by N,N'-diacetyl-L-cystine, L-cystine di-beta-naphthylamide, disulfiram, N-acetyl-L-cystine, 2,2-dithiodipyridine, 4,4-dithiodipyridine, L- and D-cysteine, and oxidized and reduced coenzyme A
Escherichia coli
Organism
EC Number
Organism
Primary Accession No. (UniProt)
Commentary
Textmining
1.2.1.11
Escherichia coli
-
-
-
Reaction
EC Number
Reaction
Commentary
Organism
1.2.1.11
L-aspartate 4-semialdehyde + phosphate + NADP+ = L-4-aspartyl phosphate + NADPH + H+
catalytic Cys135 is essential for activity
Escherichia coli
Substrates and Products (Substrate)
EC Number
Substrates
Commentary Substrates
Literature (Substrates)
Organism
Products
Commentary (Products)
Literature (Products)
Organism (Products)
Reversibility
1.2.1.11
L-aspartate-4-semialdehyde + phosphate + NADP+
-
654891
Escherichia coli
L-4-aspartyl phosphate + NADPH
reverse reaction: reductive dephosphorylation
-
-
r
Temperature Optimum [°C]
EC Number
Temperature Optimum [°C]
Temperature Optimum Maximum [°C]
Commentary
Organism
1.2.1.11
30
-
assay at
Escherichia coli
pH Optimum
EC Number
pH Optimum Minimum
pH Optimum Maximum
Commentary
Organism
1.2.1.11
7.5
-
assay at
Escherichia coli
Cofactor
EC Number
Cofactor
Commentary
Organism
Structure
1.2.1.11
NADP+
-
Escherichia coli
1.2.1.11
NADPH
-
Escherichia coli
Ki Value [mM]
EC Number
Ki Value [mM]
Ki Value maximum [mM]
Inhibitor
Commentary
Organism
Structure
1.2.1.11
additional information
-
additional information
inhibition kinetics at 21°C and pH 7.5
Escherichia coli
Cofactor (protein specific)
EC Number
Cofactor
Commentary
Organism
Structure
1.2.1.11
NADP+
-
Escherichia coli
1.2.1.11
NADPH
-
Escherichia coli
Inhibitors (protein specific)
EC Number
Inhibitors
Commentary
Organism
Structure
1.2.1.11
D-Cystine
70% inhibition at 0.01 mM, binds via the cysteine moiety covalently to the catalytic Cys135 of the enzyme, pH-dependent proces, optimal at pH 7.0-7.5, inhibition is reversible by DTT, dithioerythritol, 2-mercaptoethanol, dimercaptopropanol, and reduced glutathione, no protection by aspartate-beta-semialdehyde, NADP+ or NADPH, inhibition mechanism and kinetics
Escherichia coli
1.2.1.11
DTNB
reversible by DTT, dithioerythritol, 2-mercaptoethanol, dimercaptopropanol, and reduced glutathione
Escherichia coli
1.2.1.11
GSSG
oxidized glutathione
Escherichia coli
1.2.1.11
L-2-Amino-4-oxo-5-chloropentanoic acid
substrate analogue, irreversible inactivation, pseudo-first-order kinetics
Escherichia coli
1.2.1.11
L-cystine
complete inhibition at 0.01 mM, binds via the cysteine moiety covalently to the catalytic Cys135 of the enzyme, pH-dependent process, optimal at pH 7.0-7.5, inhibition is reversible by DTT, dithioerythritol, 2-mercaptoethanol, dimercaptopropanol, and reduced glutathione, no protection by aspartate-beta-semialdehyde, NADP+ or NADPH, inhibition mechanism and kinetics
Escherichia coli
1.2.1.11
L-cystine diethyl ester
68% inhibition at 0.01 mM, reversible by DTT, dithioerythritol, 2-mercaptoethanol, dimercaptopropanol, and reduced glutathione
Escherichia coli
1.2.1.11
L-cystine dimethyl ester
67% inhibition at 0.01 mM, reversible by DTT, dithioerythritol, 2-mercaptoethanol, dimercaptopropanol, and reduced glutathione
Escherichia coli
1.2.1.11
L-cystine hydroxamate
20% inhibition at 0.01 mM, reversible by DTT, dithioerythritol, 2-mercaptoethanol, dimercaptopropanol, and reduced glutathione
Escherichia coli
1.2.1.11
additional information
no inhibition by N,N'-diacetyl-L-cystine, L-cystine di-beta-naphthylamide, disulfiram, N-acetyl-L-cystine, 2,2-dithiodipyridine, 4,4-dithiodipyridine, L- and D-cysteine, and oxidized and reduced coenzyme A
Escherichia coli
Ki Value [mM] (protein specific)
EC Number
Ki Value [mM]
Ki Value maximum [mM]
Inhibitor
Commentary
Organism
Structure
1.2.1.11
additional information
-
additional information
inhibition kinetics at 21°C and pH 7.5
Escherichia coli
Substrates and Products (Substrate) (protein specific)
EC Number
Substrates
Commentary Substrates
Literature (Substrates)
Organism
Products
Commentary (Products)
Literature (Products)
Organism (Products)
Reversibility
1.2.1.11
L-aspartate-4-semialdehyde + phosphate + NADP+
-
654891
Escherichia coli
L-4-aspartyl phosphate + NADPH
reverse reaction: reductive dephosphorylation
-
-
r
Temperature Optimum [°C] (protein specific)
EC Number
Temperature Optimum [°C]
Temperature Optimum Maximum [°C]
Commentary
Organism
1.2.1.11
30
-
assay at
Escherichia coli
pH Optimum (protein specific)
EC Number
pH Optimum Minimum
pH Optimum Maximum
Commentary
Organism
1.2.1.11
7.5
-
assay at
Escherichia coli