BRENDA - Enzyme Database show

Irreversible inhibition of dihydrodipicolinate synthase by 4-oxo-heptenedioic acid analogues

Boughton, B.A.; Griffin, M.D.; ODonnell, P.A.; Dobson, R.C.; Perugini, M.A.; Gerrard, J.A.; Hutton, C.A.; Bioorg. Med. Chem. 16, 9975-9983 (2008)

Data extracted from this reference:

Inhibitors
EC Number
Inhibitors
Commentary
Organism
Structure
4.3.3.7
(2E)-4-oxohept-2-enedioic acid
-
Escherichia coli
4.3.3.7
(2E,5E)-4-oxohepta-2,5-dienedioic acid
-
Escherichia coli
4.3.3.7
diethyl (2E)-4-oxohept-2-enedioate
-
Escherichia coli
4.3.3.7
diethyl (2E,5E)-4-oxohepta-2,5-dienedioate
-
Escherichia coli
4.3.3.7
additional information
inhibition studies by using 4-oxo-heptenedioic acid analogues, determination of second-order rate constants of inactivation, substrate co-incubation studies show that the inhibitors act at the active-site, interaction analyzed by mass spectrometry, sites of enzyme alkylation determined
Escherichia coli
Organism
EC Number
Organism
Primary Accession No. (UniProt)
Commentary
Textmining
4.3.3.7
Escherichia coli
P0A6L2
-
-
Specific Activity [micromol/min/mg]
EC Number
Specific Activity Minimum [Ámol/min/mg]
Specific Activity Maximum [Ámol/min/mg]
Commentary
Organism
4.3.3.7
additional information
-
substrate protection experiments, inhibition by alkylation the active-site lysine residue (Lys161) and a surface cysteine residue, slower alkylation of other cysteine residues with lower surface accessibility, co-incubation of the enzyme with the inhibitors in the presence of pyruvate protect against active-site alkylation and cysteine residues
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
L-aspartate 4-semialdehyde + pyruvate
substrate protection and inhibition experiments
691243
Escherichia coli
dihydrodipicolinate + H2O
-
-
-
?
Ki Value [mM]
EC Number
Ki Value [mM]
Ki Value maximum [mM]
Inhibitor
Commentary
Organism
Structure
4.3.3.7
1.63
-
(2E,5E)-4-oxohepta-2,5-dienedioic acid
more potent than the corresponding mono-ene inhibitors
Escherichia coli
4.3.3.7
4.95
-
diethyl (2E,5E)-4-oxohepta-2,5-dienedioate
best inhibitor
Escherichia coli
4.3.3.7
10.9
-
diethyl (2E)-4-oxohept-2-enedioate
mono-ene inhibitor
Escherichia coli
4.3.3.7
32.4
-
(2E)-4-oxohept-2-enedioic acid
mono-ene inhibitor
Escherichia coli
Inhibitors (protein specific)
EC Number
Inhibitors
Commentary
Organism
Structure
4.3.3.7
(2E)-4-oxohept-2-enedioic acid
-
Escherichia coli
4.3.3.7
(2E,5E)-4-oxohepta-2,5-dienedioic acid
-
Escherichia coli
4.3.3.7
diethyl (2E)-4-oxohept-2-enedioate
-
Escherichia coli
4.3.3.7
diethyl (2E,5E)-4-oxohepta-2,5-dienedioate
-
Escherichia coli
4.3.3.7
additional information
inhibition studies by using 4-oxo-heptenedioic acid analogues, determination of second-order rate constants of inactivation, substrate co-incubation studies show that the inhibitors act at the active-site, interaction analyzed by mass spectrometry, sites of enzyme alkylation determined
Escherichia coli
Ki Value [mM] (protein specific)
EC Number
Ki Value [mM]
Ki Value maximum [mM]
Inhibitor
Commentary
Organism
Structure
4.3.3.7
1.63
-
(2E,5E)-4-oxohepta-2,5-dienedioic acid
more potent than the corresponding mono-ene inhibitors
Escherichia coli
4.3.3.7
4.95
-
diethyl (2E,5E)-4-oxohepta-2,5-dienedioate
best inhibitor
Escherichia coli
4.3.3.7
10.9
-
diethyl (2E)-4-oxohept-2-enedioate
mono-ene inhibitor
Escherichia coli
4.3.3.7
32.4
-
(2E)-4-oxohept-2-enedioic acid
mono-ene inhibitor
Escherichia coli
Specific Activity [micromol/min/mg] (protein specific)
EC Number
Specific Activity Minimum [Ámol/min/mg]
Specific Activity Maximum [Ámol/min/mg]
Commentary
Organism
4.3.3.7
additional information
-
substrate protection experiments, inhibition by alkylation the active-site lysine residue (Lys161) and a surface cysteine residue, slower alkylation of other cysteine residues with lower surface accessibility, co-incubation of the enzyme with the inhibitors in the presence of pyruvate protect against active-site alkylation and cysteine residues
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
L-aspartate 4-semialdehyde + pyruvate
substrate protection and inhibition experiments
691243
Escherichia coli
dihydrodipicolinate + H2O
-
-
-
?