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Literature summary for 4.3.3.7 extracted from

  • Boughton, B.A.; Hor, L.; Gerrard, J.A.; Hutton, C.A.
    1,3-Phenylene bis(ketoacid) derivatives as inhibitors of Escherichia coli dihydrodipicolinate synthase (2012), Bioorg. Med. Chem., 20, 2419-2426.
    View publication on PubMed

Inhibitors

Inhibitors Comment Organism Structure
2,2'-(2-hydroxy-1,3-phenylene)bis(2-oxoacetic acid) slow-tight inhibition Escherichia coli
2,2'-benzene-1,3-diylbis(oxoacetic acid) slow inhibition Escherichia coli
dimethyl-(2E,2'E)-2,2'-benzene-1,3-diylbis[(hydroxyimino)ethanoate] slow inhibition Escherichia coli
dimethyl-2,2'-(2-hydroxy-1,3-phenylene)bis(2-oxoacetate) slow-tight inhibition Escherichia coli
additional information 1,3-phenylene bis(ketoacid) derivatives as enzyme inhibitors, overview. Ketoacid derivatives act as slow and slow-tight binding inhibitors with either an encounter complex or a condensation product for the slow and slow-tight binding inhibitors, respectively, modeling, overview. No or poor inhibition by dimethyl 2,2'-benzene-1,3-diylbis(oxoacetate), (2E,2'E)-2,2'-benzene-1,3-diylbis[(hydroxyimino)ethanoic acid], and dimethyl-2,2'-(2-methoxy-1,3-phenylene)bis(2-oxoacetate) Escherichia coli

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
(S)-aspartate-4-semialdehyde + pyruvate Escherichia coli the enzyme-catalyzed reaction is initiated by condensation of pyruvate with an active site Lys161 forming a Schiff base. Subsequent tautomerization to the enamine and aldol-type reaction with (S)-aspartate-4-semialdehyde then generates an acyclic enzyme-bound intermediate. Transimination of the acyclic intermediate yields the cyclic alcohol (4S)-4-hydroxy-2,3,4,5-tetrahydro-(2S)-dipicolinic acid, with simultaneous release of the active site lysine residue (2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinic acid + H2O
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?

Organism

Organism UniProt Comment Textmining
Escherichia coli
-
-
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
(S)-aspartate-4-semialdehyde + pyruvate
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Escherichia coli (2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinic acid + H2O
-
?
(S)-aspartate-4-semialdehyde + pyruvate the enzyme-catalyzed reaction is initiated by condensation of pyruvate with an active site Lys161 forming a Schiff base. Subsequent tautomerization to the enamine and aldol-type reaction with (S)-aspartate-4-semialdehyde then generates an acyclic enzyme-bound intermediate. Transimination of the acyclic intermediate yields the cyclic alcohol (4S)-4-hydroxy-2,3,4,5-tetrahydro-(2S)-dipicolinic acid, with simultaneous release of the active site lysine residue Escherichia coli (2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinic acid + H2O
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?

Synonyms

Synonyms Comment Organism
DHDPS
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Escherichia coli
dihydrodipicolinate synthase
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Escherichia coli

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
30
-
assay at Escherichia coli

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
8
-
assay at Escherichia coli

Ki Value [mM]

Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
0.04
-
dimethyl-2,2'-(2-hydroxy-1,3-phenylene)bis(2-oxoacetate) pH 8.0, 30°C Escherichia coli
0.29
-
2,2'-(2-hydroxy-1,3-phenylene)bis(2-oxoacetic acid) pH 8.0, 30°C Escherichia coli
0.33
-
dimethyl-(2E,2'E)-2,2'-benzene-1,3-diylbis[(hydroxyimino)ethanoate] pH 8.0, 30°C Escherichia coli
2.96
-
2,2'-benzene-1,3-diylbis(oxoacetic acid) pH 8.0, 30°C Escherichia coli

General Information

General Information Comment Organism
metabolism dihydrodipicolinate synthase is a key enzyme in the lysine biosynthesis pathway that catalyzes the condensation of pyruvate and aspartate semi-aldehyde Escherichia coli