Literature summary extracted from
Sridharan, U.; Ebihara, A.; Kuramitsu, S.; Yokoyama, S.; Kumarevel, T.; Ponnuraj, K.
Crystal structure and in silico studies of dihydrodipicolinate synthase (DHDPS) from Aquifex aeolicus (2014), Extremophiles, 18, 973-985.
Application
| EC Number |
Application |
Comment |
Organism |
|---|
| 4.3.3.7 |
drug development |
the enzyme is an attractive target for rational antibiotic and herbicide design |
Aquifex aeolicus |
| 4.3.3.7 |
synthesis |
the enzyme can be commercially exploited for high-yield production of (S)-lysine |
Aquifex aeolicus |
Cloned(Commentary)
| EC Number |
Cloned (Comment) |
Organism |
|---|
| 4.3.3.7 |
gene dapA or Aq_1143, sequence comparisons, recombinant enzyme expression in Escherichia coli strain BL21-CodonPlus (DE3)-RIL |
Aquifex aeolicus |
Crystallization (Commentary)
| EC Number |
Crystallization (Comment) |
Organism |
|---|
| 4.3.3.7 |
purified recombinant enzyme, sitting drop vapour diffusion method, mixing of 0.001 ml of 21.8 mg/ml protein in 20 mM Tris-HCl at pH 8.0 and 0.2 M NaCl, with 0.001 ml of reservoir solution containing 4 M sodium phosphate, 0.1 M imidazole, and 0.2 M NaCl at pH 8.0, 18°C, 1 week, X-ray diffraction structure determination and analysis at 1.90 A resolution, molecular replacement |
Aquifex aeolicus |
Protein Variants
| EC Number |
Protein Variants |
Comment |
Organism |
|---|
| 4.3.3.7 |
C139A |
site-directed in silico mutation |
Aquifex aeolicus |
General Stability
| EC Number |
General Stability |
Organism |
|---|
| 4.3.3.7 |
molecular dynamics simulation to analyze the stability of the enzyme |
Aquifex aeolicus |
Inhibitors
| EC Number |
Inhibitors |
Comment |
Organism |
Structure |
|---|
| 4.3.3.7 |
(S)-lysine |
feedback inhibitor, docking study with enzyme crystals |
Aquifex aeolicus |
|
Natural Substrates/ Products (Substrates)
| EC Number |
Natural Substrates |
Organism |
Comment (Nat. Sub.) |
Natural Products |
Comment (Nat. Pro.) |
Rev. |
Reac. |
|---|
| 4.3.3.7 |
(S)-aspartate-4-semialdehyde + pyruvate |
Aquifex aeolicus |
- |
(2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinic acid + H2O |
- |
? |
|
Organism
| EC Number |
Organism |
UniProt |
Comment |
Textmining |
|---|
| 4.3.3.7 |
Aquifex aeolicus |
O67216 |
gene dapA or Aq_1143 |
- |
Purification (Commentary)
| EC Number |
Purification (Comment) |
Organism |
|---|
| 4.3.3.7 |
recombinant enzyme from Escherichia coli strain BL21-CodonPlus (DE3)-RIL by two different steps of anion exchange chromatography, dialysis, hydroxyapatite chromatography, another step of anion exchange chromatography, and gel filtration, to homogeneity |
Aquifex aeolicus |
Reaction
| EC Number |
Reaction |
Comment |
Organism |
Reaction ID |
|---|
| 4.3.3.7 |
pyruvate + L-aspartate-4-semialdehyde = (2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinate + H2O |
reaction steps, overview |
Aquifex aeolicus |
|
Substrates and Products (Substrate)
| EC Number |
Substrates |
Comment Substrates |
Organism |
Products |
Comment (Products) |
Rev. |
Reac. |
|---|
| 4.3.3.7 |
(S)-aspartate-4-semialdehyde + pyruvate |
- |
Aquifex aeolicus |
(2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinic acid + H2O |
- |
? |
|
Subunits
| EC Number |
Subunits |
Comment |
Organism |
|---|
| 4.3.3.7 |
tetramer |
the overall quaternary structure of the enzyme consists of four crystallographically independent molecules (A, C, D, and E) forming dimer of dimers. The monomer exhibits a TIM barrel fold and comprises of 11 alpha helices built by 146 amino acids out of which the first 8 helices form the TIM barrel domain and remaining three helices present in the C-terminal. The monomer also has 10 beta strands composed of 42 amino acids. The enzyme molecule has two types of dimer interfaces, weak-dimer interface and tight-dimer interfaces, structure model, overview |
Aquifex aeolicus |
Synonyms
| EC Number |
Synonyms |
Comment |
Organism |
|---|
| 4.3.3.7 |
Aq_1143 |
- |
Aquifex aeolicus |
| 4.3.3.7 |
DHDPS |
- |
Aquifex aeolicus |
| 4.3.3.7 |
dihydrodipicolinate synthase |
- |
Aquifex aeolicus |
Temperature Stability [°C]
| EC Number |
Temperature Stability Minimum [°C] |
Temperature Stability Maximum [°C] |
Comment |
Organism |
|---|
| 4.3.3.7 |
90 |
- |
the enzyme is stable up to, high-temperature molecular dynamics simulation of the wild-type and mutant enzymes |
Aquifex aeolicus |
General Information
| EC Number |
General Information |
Comment |
Organism |
|---|
| 4.3.3.7 |
metabolism |
the enzyme catalyses the first committed step in the lysine biosynthesis pathway, the condensation of pyruvate and (S)-aspartate semialdehyde to form (4S)-4-hydroxy-2,3,4,5-tetrahydro-(2S)-dipicolinic acid |
Aquifex aeolicus |
| 4.3.3.7 |
additional information |
the enzyme has unique disulfide linkage which is critical for the stability of the enzyme tetramer, but is not conserved in homologous enzymes, molecular dynamics simulation of the native structure of the enzyme tetramer and dimeric units containing complexes of enzyme-pyruvate or enzyme-lysine, enzyme structure comparisons and ligand docking analysis, overview |
Aquifex aeolicus |
| 4.3.3.7 |
physiological function |
the enzyme catalyzes a rate-limiting step in the (S)-lysine biosynthetic pathway, which is regulated by a feedback mechanism through lysine |
Aquifex aeolicus |
