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Literature summary for 4.3.3.7 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.
    View publication on PubMed

Application

Application Comment Organism
drug development the enzyme is an attractive target for rational antibiotic and herbicide design Aquifex aeolicus
synthesis the enzyme can be commercially exploited for high-yield production of (S)-lysine Aquifex aeolicus

Cloned(Commentary)

Cloned (Comment) Organism
gene dapA or Aq_1143, sequence comparisons, recombinant enzyme expression in Escherichia coli strain BL21-CodonPlus (DE3)-RIL Aquifex aeolicus

Crystallization (Commentary)

Crystallization (Comment) Organism
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

Protein Variants Comment Organism
C139A site-directed in silico mutation Aquifex aeolicus

General Stability

General Stability Organism
molecular dynamics simulation to analyze the stability of the enzyme Aquifex aeolicus

Inhibitors

Inhibitors Comment Organism Structure
(S)-lysine feedback inhibitor, docking study with enzyme crystals Aquifex aeolicus

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
(S)-aspartate-4-semialdehyde + pyruvate Aquifex aeolicus
-
(2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinic acid + H2O
-
?

Organism

Organism UniProt Comment Textmining
Aquifex aeolicus O67216 gene dapA or Aq_1143
-

Purification (Commentary)

Purification (Comment) Organism
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

Reaction Comment Organism Reaction ID
pyruvate + L-aspartate-4-semialdehyde = (2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinate + H2O reaction steps, overview Aquifex aeolicus

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
(S)-aspartate-4-semialdehyde + pyruvate
-
Aquifex aeolicus (2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinic acid + H2O
-
?

Subunits

Subunits Comment Organism
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

Synonyms Comment Organism
Aq_1143
-
Aquifex aeolicus
DHDPS
-
Aquifex aeolicus
dihydrodipicolinate synthase
-
Aquifex aeolicus

Temperature Stability [°C]

Temperature Stability Minimum [°C] Temperature Stability Maximum [°C] Comment Organism
90
-
the enzyme is stable up to, high-temperature molecular dynamics simulation of the wild-type and mutant enzymes Aquifex aeolicus

General Information

General Information Comment Organism
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
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
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