BRENDA - Enzyme Database show

NMR studies uncover alternate substrates for dihydrodipicolinate synthase and suggest that dihydrodipicolinate reductase is also a dehydratase

Devenish, S.R.; Blunt, J.W.; Gerrard, J.A.; J. Med. Chem. 53, 4808-4812 (2010)

Data extracted from this reference:

Inhibitors
EC Number
Inhibitors
Commentary
Organism
Structure
4.3.3.7
2-oxobutyrate
competitive inhibitor of DHDPS
Escherichia coli
4.3.3.7
2-oxoglutarate
competitive inhibitor of DHDPS
Escherichia coli
4.3.3.7
3-Fluoropyruvate
competitive inhibitor of DHDPS, and a competitive substrates
Escherichia coli
4.3.3.7
3-hydroxypyruvate
competitive inhibitor of DHDPS and a competitive substrate
Escherichia coli
4.3.3.7
Bromopyruvate
is an irreversible inhibitor of DHDPS
Escherichia coli
4.3.3.7
additional information
the substrate specificity of the enzyme, two pyruvate analogues, previously classified as weak competitive inhibitors, are turned over productively by DHDPS, NMR spectroscopy, overview
Escherichia coli
Natural Substrates/ Products (Substrates)
EC Number
Natural Substrates
Organism
Commentary (Nat. Sub.)
Natural Products
Commentary (Nat. Pro.)
Organism (Nat. Pro.)
Reversibility
1.17.1.8
additional information
Escherichia coli
DHDPR accepts (4S)-4-hydroxy-2,3,4,5-tetrahydro-(2S)-dipicolinic acid as true substrate rather than dihydrodipicolinate, suggesting that DHDPR catalyzes an overall deoxygenation reaction, likely by a dehydratase-reductase route, substrate specificity, overview. A critical role is played by residue His 159 in the catalytic mechanism of DHDPR. Replacement of this residue with an alanine or a glutamine is reported to result in a 150-200fold reduction in catalytic rate as well as a 6fold increase in KM. His 159 has been proposed to act as a general acid during catalysis, providing the proton required after hydride addition. No activity with beta-hydroxypyruvate and 3-fluoropyruvate
?
-
-
-
4.3.3.7
L-aspartate 4-semialdehyde + pyruvate
Escherichia coli
-
(S)-2,3-dihydropyridine-2,6-dicarboxylate + 2 H2O
-
-
?
Organism
EC Number
Organism
Primary Accession No. (UniProt)
Commentary
Textmining
1.17.1.8
Escherichia coli
-
-
-
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
1.17.1.8
additional information
DHDPR accepts (4S)-4-hydroxy-2,3,4,5-tetrahydro-(2S)-dipicolinic acid as true substrate rather than dihydrodipicolinate, suggesting that DHDPR catalyzes an overall deoxygenation reaction, likely by a dehydratase-reductase route, substrate specificity, overview. A critical role is played by residue His 159 in the catalytic mechanism of DHDPR. Replacement of this residue with an alanine or a glutamine is reported to result in a 150-200fold reduction in catalytic rate as well as a 6fold increase in KM. His 159 has been proposed to act as a general acid during catalysis, providing the proton required after hydride addition. No activity with beta-hydroxypyruvate and 3-fluoropyruvate
712704
Escherichia coli
?
-
-
-
-
4.3.3.7
L-aspartate 4-semialdehyde + pyruvate
-
712704
Escherichia coli
(S)-2,3-dihydropyridine-2,6-dicarboxylate + 2 H2O
-
-
-
?
Subunits
EC Number
Subunits
Commentary
Organism
1.17.1.8
More
crystal structure modelling and analysis, PDB ID 1ARZ, overview
Escherichia coli
Temperature Optimum [°C]
EC Number
Temperature Optimum [°C]
Temperature Optimum Maximum [°C]
Commentary
Organism
4.3.3.7
23
-
assay at
Escherichia coli
pH Optimum
EC Number
pH Optimum Minimum
pH Optimum Maximum
Commentary
Organism
1.17.1.8
8
-
dehydration assay at
Escherichia coli
4.3.3.7
8
-
assay at
Escherichia coli
Inhibitors (protein specific)
EC Number
Inhibitors
Commentary
Organism
Structure
4.3.3.7
2-oxobutyrate
competitive inhibitor of DHDPS
Escherichia coli
4.3.3.7
2-oxoglutarate
competitive inhibitor of DHDPS
Escherichia coli
4.3.3.7
3-Fluoropyruvate
competitive inhibitor of DHDPS, and a competitive substrates
Escherichia coli
4.3.3.7
3-hydroxypyruvate
competitive inhibitor of DHDPS and a competitive substrate
Escherichia coli
4.3.3.7
Bromopyruvate
is an irreversible inhibitor of DHDPS
Escherichia coli
4.3.3.7
additional information
the substrate specificity of the enzyme, two pyruvate analogues, previously classified as weak competitive inhibitors, are turned over productively by DHDPS, NMR spectroscopy, overview
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
1.17.1.8
additional information
Escherichia coli
DHDPR accepts (4S)-4-hydroxy-2,3,4,5-tetrahydro-(2S)-dipicolinic acid as true substrate rather than dihydrodipicolinate, suggesting that DHDPR catalyzes an overall deoxygenation reaction, likely by a dehydratase-reductase route, substrate specificity, overview. A critical role is played by residue His 159 in the catalytic mechanism of DHDPR. Replacement of this residue with an alanine or a glutamine is reported to result in a 150-200fold reduction in catalytic rate as well as a 6fold increase in KM. His 159 has been proposed to act as a general acid during catalysis, providing the proton required after hydride addition. No activity with beta-hydroxypyruvate and 3-fluoropyruvate
?
-
-
-
4.3.3.7
L-aspartate 4-semialdehyde + pyruvate
Escherichia coli
-
(S)-2,3-dihydropyridine-2,6-dicarboxylate + 2 H2O
-
-
?
Substrates and Products (Substrate) (protein specific)
EC Number
Substrates
Commentary Substrates
Literature (Substrates)
Organism
Products
Commentary (Products)
Literature (Products)
Organism (Products)
Reversibility
1.17.1.8
additional information
DHDPR accepts (4S)-4-hydroxy-2,3,4,5-tetrahydro-(2S)-dipicolinic acid as true substrate rather than dihydrodipicolinate, suggesting that DHDPR catalyzes an overall deoxygenation reaction, likely by a dehydratase-reductase route, substrate specificity, overview. A critical role is played by residue His 159 in the catalytic mechanism of DHDPR. Replacement of this residue with an alanine or a glutamine is reported to result in a 150-200fold reduction in catalytic rate as well as a 6fold increase in KM. His 159 has been proposed to act as a general acid during catalysis, providing the proton required after hydride addition. No activity with beta-hydroxypyruvate and 3-fluoropyruvate
712704
Escherichia coli
?
-
-
-
-
4.3.3.7
L-aspartate 4-semialdehyde + pyruvate
-
712704
Escherichia coli
(S)-2,3-dihydropyridine-2,6-dicarboxylate + 2 H2O
-
-
-
?
Subunits (protein specific)
EC Number
Subunits
Commentary
Organism
1.17.1.8
More
crystal structure modelling and analysis, PDB ID 1ARZ, overview
Escherichia coli
Temperature Optimum [°C] (protein specific)
EC Number
Temperature Optimum [°C]
Temperature Optimum Maximum [°C]
Commentary
Organism
4.3.3.7
23
-
assay at
Escherichia coli
pH Optimum (protein specific)
EC Number
pH Optimum Minimum
pH Optimum Maximum
Commentary
Organism
1.17.1.8
8
-
dehydration assay at
Escherichia coli
4.3.3.7
8
-
assay at
Escherichia coli
General Information
EC Number
General Information
Commentary
Organism
1.17.1.8
metabolism
DHDPR is central to the diaminopimelate pathway for lysine biosynthesis
Escherichia coli
1.17.1.8
additional information
NMR studies uncover that dihydrodipicolinate reductase is also a dehydratase, overview
Escherichia coli
General Information (protein specific)
EC Number
General Information
Commentary
Organism
1.17.1.8
metabolism
DHDPR is central to the diaminopimelate pathway for lysine biosynthesis
Escherichia coli
1.17.1.8
additional information
NMR studies uncover that dihydrodipicolinate reductase is also a dehydratase, overview
Escherichia coli