BRENDA - Enzyme Database show

1,3-Phenylene bis(ketoacid) derivatives as inhibitors of Escherichia coli dihydrodipicolinate synthase

Boughton, B.A.; Hor, L.; Gerrard, J.A.; Hutton, C.A.; Bioorg. Med. Chem. 20, 2419-2426 (2012)

Data extracted from this reference:

Inhibitors
EC Number
Inhibitors
Commentary
Organism
Structure
4.3.3.7
2,2'-(2-hydroxy-1,3-phenylene)bis(2-oxoacetic acid)
slow-tight inhibition
Escherichia coli
4.3.3.7
2,2'-benzene-1,3-diylbis(oxoacetic acid)
slow inhibition
Escherichia coli
4.3.3.7
dimethyl-(2E,2'E)-2,2'-benzene-1,3-diylbis[(hydroxyimino)ethanoate]
slow inhibition
Escherichia coli
4.3.3.7
dimethyl-2,2'-(2-hydroxy-1,3-phenylene)bis(2-oxoacetate)
slow-tight inhibition
Escherichia coli
4.3.3.7
additional information
1,3-phenylene bis(ketoacid) derivatives as enzyme inhibitors, overview. Ketoacid derivatives act as slow and slow-tight binding inhibitors with either an encounter complex or a condensation product for the slow and slow-tight binding inhibitors, respectively, modeling, overview. No or poor inhibition by dimethyl 2,2'-benzene-1,3-diylbis(oxoacetate), (2E,2'E)-2,2'-benzene-1,3-diylbis[(hydroxyimino)ethanoic acid], and dimethyl-2,2'-(2-methoxy-1,3-phenylene)bis(2-oxoacetate)
Escherichia coli
Natural Substrates/ Products (Substrates)
EC Number
Natural Substrates
Organism
Commentary (Nat. Sub.)
Natural Products
Commentary (Nat. Pro.)
Organism (Nat. Pro.)
Reversibility
4.3.3.7
(S)-aspartate-4-semialdehyde + pyruvate
Escherichia coli
the enzyme-catalyzed reaction is initiated by condensation of pyruvate with an active site Lys161 forming a Schiff base. Subsequent tautomerization to the enamine and aldol-type reaction with (S)-aspartate-4-semialdehyde then generates an acyclic enzyme-bound intermediate. Transimination of the acyclic intermediate yields the cyclic alcohol (4S)-4-hydroxy-2,3,4,5-tetrahydro-(2S)-dipicolinic acid, with simultaneous release of the active site lysine residue
(2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinic acid + H2O
-
-
?
Organism
EC Number
Organism
Primary Accession No. (UniProt)
Commentary
Textmining
4.3.3.7
Escherichia coli
-
-
-
Substrates and Products (Substrate)
EC Number
Substrates
Commentary Substrates
Literature (Substrates)
Organism
Products
Commentary (Products)
Literature (Products)
Organism (Products)
Reversibility
4.3.3.7
(S)-aspartate-4-semialdehyde + pyruvate
-
729385
Escherichia coli
(2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinic acid + H2O
-
-
-
?
4.3.3.7
(S)-aspartate-4-semialdehyde + pyruvate
the enzyme-catalyzed reaction is initiated by condensation of pyruvate with an active site Lys161 forming a Schiff base. Subsequent tautomerization to the enamine and aldol-type reaction with (S)-aspartate-4-semialdehyde then generates an acyclic enzyme-bound intermediate. Transimination of the acyclic intermediate yields the cyclic alcohol (4S)-4-hydroxy-2,3,4,5-tetrahydro-(2S)-dipicolinic acid, with simultaneous release of the active site lysine residue
729385
Escherichia coli
(2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinic acid + H2O
-
-
-
?
Temperature Optimum [°C]
EC Number
Temperature Optimum [°C]
Temperature Optimum Maximum [°C]
Commentary
Organism
4.3.3.7
30
-
assay at
Escherichia coli
pH Optimum
EC Number
pH Optimum Minimum
pH Optimum Maximum
Commentary
Organism
4.3.3.7
8
-
assay at
Escherichia coli
Ki Value [mM]
EC Number
Ki Value [mM]
Ki Value maximum [mM]
Inhibitor
Commentary
Organism
Structure
4.3.3.7
0.04
-
dimethyl-2,2'-(2-hydroxy-1,3-phenylene)bis(2-oxoacetate)
pH 8.0, 30°C
Escherichia coli
4.3.3.7
0.29
-
2,2'-(2-hydroxy-1,3-phenylene)bis(2-oxoacetic acid)
pH 8.0, 30°C
Escherichia coli
4.3.3.7
0.33
-
dimethyl-(2E,2'E)-2,2'-benzene-1,3-diylbis[(hydroxyimino)ethanoate]
pH 8.0, 30°C
Escherichia coli
4.3.3.7
2.96
-
2,2'-benzene-1,3-diylbis(oxoacetic acid)
pH 8.0, 30°C
Escherichia coli
Inhibitors (protein specific)
EC Number
Inhibitors
Commentary
Organism
Structure
4.3.3.7
2,2'-(2-hydroxy-1,3-phenylene)bis(2-oxoacetic acid)
slow-tight inhibition
Escherichia coli
4.3.3.7
2,2'-benzene-1,3-diylbis(oxoacetic acid)
slow inhibition
Escherichia coli
4.3.3.7
dimethyl-(2E,2'E)-2,2'-benzene-1,3-diylbis[(hydroxyimino)ethanoate]
slow inhibition
Escherichia coli
4.3.3.7
dimethyl-2,2'-(2-hydroxy-1,3-phenylene)bis(2-oxoacetate)
slow-tight inhibition
Escherichia coli
4.3.3.7
additional information
1,3-phenylene bis(ketoacid) derivatives as enzyme inhibitors, overview. Ketoacid derivatives act as slow and slow-tight binding inhibitors with either an encounter complex or a condensation product for the slow and slow-tight binding inhibitors, respectively, modeling, overview. No or poor inhibition by dimethyl 2,2'-benzene-1,3-diylbis(oxoacetate), (2E,2'E)-2,2'-benzene-1,3-diylbis[(hydroxyimino)ethanoic acid], and dimethyl-2,2'-(2-methoxy-1,3-phenylene)bis(2-oxoacetate)
Escherichia coli
Ki Value [mM] (protein specific)
EC Number
Ki Value [mM]
Ki Value maximum [mM]
Inhibitor
Commentary
Organism
Structure
4.3.3.7
0.04
-
dimethyl-2,2'-(2-hydroxy-1,3-phenylene)bis(2-oxoacetate)
pH 8.0, 30°C
Escherichia coli
4.3.3.7
0.29
-
2,2'-(2-hydroxy-1,3-phenylene)bis(2-oxoacetic acid)
pH 8.0, 30°C
Escherichia coli
4.3.3.7
0.33
-
dimethyl-(2E,2'E)-2,2'-benzene-1,3-diylbis[(hydroxyimino)ethanoate]
pH 8.0, 30°C
Escherichia coli
4.3.3.7
2.96
-
2,2'-benzene-1,3-diylbis(oxoacetic acid)
pH 8.0, 30°C
Escherichia coli
Natural Substrates/ Products (Substrates) (protein specific)
EC Number
Natural Substrates
Organism
Commentary (Nat. Sub.)
Natural Products
Commentary (Nat. Pro.)
Organism (Nat. Pro.)
Reversibility
4.3.3.7
(S)-aspartate-4-semialdehyde + pyruvate
Escherichia coli
the enzyme-catalyzed reaction is initiated by condensation of pyruvate with an active site Lys161 forming a Schiff base. Subsequent tautomerization to the enamine and aldol-type reaction with (S)-aspartate-4-semialdehyde then generates an acyclic enzyme-bound intermediate. Transimination of the acyclic intermediate yields the cyclic alcohol (4S)-4-hydroxy-2,3,4,5-tetrahydro-(2S)-dipicolinic acid, with simultaneous release of the active site lysine residue
(2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinic acid + H2O
-
-
?
Substrates and Products (Substrate) (protein specific)
EC Number
Substrates
Commentary Substrates
Literature (Substrates)
Organism
Products
Commentary (Products)
Literature (Products)
Organism (Products)
Reversibility
4.3.3.7
(S)-aspartate-4-semialdehyde + pyruvate
-
729385
Escherichia coli
(2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinic acid + H2O
-
-
-
?
4.3.3.7
(S)-aspartate-4-semialdehyde + pyruvate
the enzyme-catalyzed reaction is initiated by condensation of pyruvate with an active site Lys161 forming a Schiff base. Subsequent tautomerization to the enamine and aldol-type reaction with (S)-aspartate-4-semialdehyde then generates an acyclic enzyme-bound intermediate. Transimination of the acyclic intermediate yields the cyclic alcohol (4S)-4-hydroxy-2,3,4,5-tetrahydro-(2S)-dipicolinic acid, with simultaneous release of the active site lysine residue
729385
Escherichia coli
(2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinic acid + H2O
-
-
-
?
Temperature Optimum [°C] (protein specific)
EC Number
Temperature Optimum [°C]
Temperature Optimum Maximum [°C]
Commentary
Organism
4.3.3.7
30
-
assay at
Escherichia coli
pH Optimum (protein specific)
EC Number
pH Optimum Minimum
pH Optimum Maximum
Commentary
Organism
4.3.3.7
8
-
assay at
Escherichia coli
General Information
EC Number
General Information
Commentary
Organism
4.3.3.7
metabolism
dihydrodipicolinate synthase is a key enzyme in the lysine biosynthesis pathway that catalyzes the condensation of pyruvate and aspartate semi-aldehyde
Escherichia coli
General Information (protein specific)
EC Number
General Information
Commentary
Organism
4.3.3.7
metabolism
dihydrodipicolinate synthase is a key enzyme in the lysine biosynthesis pathway that catalyzes the condensation of pyruvate and aspartate semi-aldehyde
Escherichia coli