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Literature summary for 1.3.5.2 extracted from

  • Hegewald, J.; Gross, U.; Bohne, W.
    Identification of dihydroorotate dehydrogenase as a relevant drug target for 1-hydroxyquinolones in Toxoplasma gondii (2013), Mol. Biochem. Parasitol., 190, 6-15.
    View publication on PubMed
Search for more literature for 1.3.5.2

Cloned(Commentary)

Cloned (Comment) Organism
expressed in Escherichia coli Bl21-CodonPlus (DE3)-RP cells Toxoplasma gondii

Protein Variants

Protein Variants Comment Organism
N302S mutation in the vicinity of the dihydroorotate binding site, sufficient to confer a partial drug resistance phenotype. 1-Hydroxyquinolones inhibit wild-type with IC50s in the nanomolar range, while theIC50s for the N302S mutant are significantly increased Toxoplasma gondii
N302S the mutant exhibits insensitivity against 1-hydroxyquinolones Toxoplasma gondii

Inhibitors

Inhibitors Comment Organism Structure
(S)-dihydroorotate
-
 Toxoplasma gondii
1-hydroxy-2-dodecyl-4(1)quinolone competitive with regard to decylubiquinone, uncompetitive with regard to dihydroorotate Toxoplasma gondii
atovaquone
-
 Toxoplasma gondii
decylubiquinone
-
 Toxoplasma gondii

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
0.015
-
 decylubiquinone mutant N302S, pH 8.0, 22°C Toxoplasma gondii
0.015
-
 decylubiquinone mutant enzyme N302S, at pH 8.0 and 25°C Toxoplasma gondii
0.037
-
 decylubiquinone wild-type, pH 8.0, 22°C Toxoplasma gondii
0.037
-
 decylubiquinone wild type enzyme, at pH 8.0 and 25°C Toxoplasma gondii
0.076
-
 (S)-dihydroorotate wild-type, pH 8.0, 22°C Toxoplasma gondii
0.076
-
 (S)-dihydroorotate wild type enzyme, at pH 8.0 and 25°C Toxoplasma gondii
0.265
-
 (S)-dihydroorotate mutant N302S, pH 8.0, 22°C Toxoplasma gondii
0.265
-
 (S)-dihydroorotate mutant enzyme N302S, at pH 8.0 and 25°C Toxoplasma gondii

Localization

Localization Comment Organism GeneOntology No. Textmining
mitochondrion
-
 Toxoplasma gondii 5739
-

Molecular Weight [Da]

Molecular Weight [Da] Molecular Weight Maximum [Da] Comment Organism
47000
-
 x * 47000, SDS-PAGE Toxoplasma gondii

Organism

Organism UniProt Comment Textmining
Toxoplasma gondii
-
-
-

Purification (Commentary)

Purification (Comment) Organism
Ni-NTA column chromatography Toxoplasma gondii

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
(S)-dihydroorotate + 2,6-dichlorophenolindophenol
-
 Toxoplasma gondii orotate + reduced 2,6-dichlorophenolindophenol
-
 ?
(S)-dihydroorotate + decylubiquinone
-
 Toxoplasma gondii orotate + decylubiquinol
-
 ?
(S)-dihydroorotate + oxidized 2,6-dichloroindophenol
-
 Toxoplasma gondii orotate + reduced 2,6-dichloroindophenol
-
 ?

Subunits

Subunits Comment Organism
? x * 47000, SDS-PAGE Toxoplasma gondii

Synonyms

Synonyms Comment Organism
DHODH
-
 Toxoplasma gondii

Turnover Number [1/s]

Turnover Number Minimum [1/s] Turnover Number Maximum [1/s] Substrate Comment Organism Structure
38
-
 (S)-dihydroorotate mutant N302S, pH 8.0, 22°C Toxoplasma gondii
38
-
 decylubiquinone mutant enzyme N302S, at pH 8.0 and 25°C Toxoplasma gondii
38
-
 (S)-dihydroorotate mutant enzyme N302S, at pH 8.0 and 25°C Toxoplasma gondii
86
-
 (S)-dihydroorotate wild-type, pH 8.0, 22°C Toxoplasma gondii
86
-
 decylubiquinone wild type enzyme, at pH 8.0 and 25°C Toxoplasma gondii
86
-
 (S)-dihydroorotate wild type enzyme, at pH 8.0 and 25°C Toxoplasma gondii

Cofactor

Cofactor Comment Organism Structure
NAD+
-
 Toxoplasma gondii

Ki Value [mM]

Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
0.000174
-
 decylubiquinone wild type enzyme, at pH 8.0 and 25°C Toxoplasma gondii
0.000333
-
 decylubiquinone mutant enzyme N302S, at pH 8.0 and 25°C Toxoplasma gondii
0.000418
-
 (S)-dihydroorotate wild type enzyme, at pH 8.0 and 25°C Toxoplasma gondii
0.001565
-
 (S)-dihydroorotate mutant enzyme N302S, at pH 8.0 and 25°C Toxoplasma gondii

IC50 Value

IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
0.000554
-
 wild type enzyme, at pH 8.0 and 25°C Toxoplasma gondii 1-hydroxy-2-dodecyl-4(1)quinolone
0.001635
-
 mutant enzyme N302S, at pH 8.0 and 25°C Toxoplasma gondii 1-hydroxy-2-dodecyl-4(1)quinolone
0.554
-
 wild-type, pH 8.0, 22°C Toxoplasma gondii 1-hydroxy-2-dodecyl-4(1)quinolone
1.635
-
 mutant N302S, pH 8.0, 22°C Toxoplasma gondii 1-hydroxy-2-dodecyl-4(1)quinolone

kcat/KM [mM/s]

kcat/KM Value [1/mMs-1] kcat/KM Value Maximum [1/mMs-1] Substrate Comment Organism Structure
140
-
 (S)-dihydroorotate mutant N302S, pH 8.0, 22°C Toxoplasma gondii
1100
-
 (S)-dihydroorotate wild-type, pH 8.0, 22°C Toxoplasma gondii
1100
-
 (S)-dihydroorotate wild type enzyme, at pH 8.0 and 25°C Toxoplasma gondii
1400
-
 (S)-dihydroorotate mutant enzyme N302S, at pH 8.0 and 25°C Toxoplasma gondii
2300
-
 decylubiquinone wild-type, pH 8.0, 22°C Toxoplasma gondii
2300
-
 decylubiquinone wild type enzyme, at pH 8.0 and 25°C Toxoplasma gondii
2500
-
 decylubiquinone mutant N302S, pH 8.0, 22°C Toxoplasma gondii
2500
-
 decylubiquinone mutant enzyme N302S, at pH 8.0 and 25°C Toxoplasma gondii