BRENDA - Enzyme Database show

Conformationally constrained diketopimelic acid analogues as inhibitors of dihydrodipicolinate synthase

Boughton, B.A.; Dobson, R.C.; Gerrard, J.A.; Hutton, C.A.; Bioorg. Med. Chem. Lett. 18, 460-463 (2008)

Data extracted from this reference:

Inhibitors
EC Number
Inhibitors
Commentary
Organism
Structure
4.3.3.7
2,2'-benzene-1,3-diylbis(oxoacetic acid)
-
Escherichia coli
4.3.3.7
dimethyl 2,2'-benzene-1,3-diylbis[(hydroxyimino)ethanoate]
-
Escherichia coli
4.3.3.7
additional information
new constrained inhibitors of DHDPS identified and tested, time-dependent inhibition and substrate protection, dimethyl 2,2'-benzene-1,3-diylbis[(hydroxyimino)ethanoate] discovered as a relatively potent inhibitor of DHDPS enzyme, validates constrained acyclic-intermediate model as a potential inhibitor lead, modifications of the aromatic ring are possible and may result in improvements in activity
Escherichia coli
Organism
EC Number
Organism
Primary Accession No. (UniProt)
Commentary
Textmining
4.3.3.7
Escherichia coli
P0A6L2
-
-
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
diketopimelic acid derivatives designed as mimics of the acyclic enzyme-bound condensation product of (S)-aspartate 4-semialdehyde and pyruvate, inhibition analysis
691294
Escherichia coli
dihydrodipicolinate + H2O
-
-
-
?
Ki Value [mM]
EC Number
Ki Value [mM]
Ki Value maximum [mM]
Inhibitor
Commentary
Organism
Structure
4.3.3.7
0.33
-
dimethyl 2,2'-benzene-1,3-diylbis[(hydroxyimino)ethanoate]
15% inhibition at 1 mM, binding with the active site lysine residue, kinetic analysis corresponds to slow-binding model of inhibition
Escherichia coli
4.3.3.7
2.96
-
2,2'-benzene-1,3-diylbis(oxoacetic acid)
49% inhibition at 5 mM, mimics the substrate pyruvate, binding with the active site lysine residue, slow inhibition
Escherichia coli
Inhibitors (protein specific)
EC Number
Inhibitors
Commentary
Organism
Structure
4.3.3.7
2,2'-benzene-1,3-diylbis(oxoacetic acid)
-
Escherichia coli
4.3.3.7
dimethyl 2,2'-benzene-1,3-diylbis[(hydroxyimino)ethanoate]
-
Escherichia coli
4.3.3.7
additional information
new constrained inhibitors of DHDPS identified and tested, time-dependent inhibition and substrate protection, dimethyl 2,2'-benzene-1,3-diylbis[(hydroxyimino)ethanoate] discovered as a relatively potent inhibitor of DHDPS enzyme, validates constrained acyclic-intermediate model as a potential inhibitor lead, modifications of the aromatic ring are possible and may result in improvements in activity
Escherichia coli
Ki Value [mM] (protein specific)
EC Number
Ki Value [mM]
Ki Value maximum [mM]
Inhibitor
Commentary
Organism
Structure
4.3.3.7
0.33
-
dimethyl 2,2'-benzene-1,3-diylbis[(hydroxyimino)ethanoate]
15% inhibition at 1 mM, binding with the active site lysine residue, kinetic analysis corresponds to slow-binding model of inhibition
Escherichia coli
4.3.3.7
2.96
-
2,2'-benzene-1,3-diylbis(oxoacetic acid)
49% inhibition at 5 mM, mimics the substrate pyruvate, binding with the active site lysine residue, slow inhibition
Escherichia coli
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
diketopimelic acid derivatives designed as mimics of the acyclic enzyme-bound condensation product of (S)-aspartate 4-semialdehyde and pyruvate, inhibition analysis
691294
Escherichia coli
dihydrodipicolinate + H2O
-
-
-
?