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Literature summary for 1.3.5.2 extracted from

  • Malmquist, N.A.; Gujjar, R.; Rathod, P.K.; Phillips, M.A.
    Analysis of flavin oxidation and electron-transfer inhibition in Plasmodium falciparum dihydroorotate dehydrogenase (2008), Biochemistry, 47, 2466-2475.
    View publication on PubMedView publication on EuropePMC

Cloned(Commentary)

Cloned (Comment) Organism
expression in Escherichia coli Plasmodium falciparum

Protein Variants

Protein Variants Comment Organism
F188A mutation decreases the affinity for Plasmodium falciparum-specific inhibitors. Pre-steady state kinetic analysis Plasmodium falciparum
F227A mutation decreases the affinity for Plasmodium falciparum-specific inhibitors. Decrease in FMN content. Pre-steady state kinetic analysis Plasmodium falciparum
H185A mutation decreases the affinity for Plasmodium falciparum-specific inhibitors. Pre-steady state kinetic analysis Plasmodium falciparum
I272A decrease in FMN content. Pre-steady state kinetic analysis Plasmodium falciparum
L531A decrease in FMN content. Pre-steady state kinetic analysis Plasmodium falciparum
R265A largest effect on Km for CoQ substrate among the mutants tested. Pre-steady state kinetic analysis Plasmodium falciparum
Y528A substantial decrease in kcat value, decrease in FMN content. Pre-steady state kinetic analysis Plasmodium falciparum
Y528F substantial decrease in kcat value, decrease in FMN content. Pre-steady state kinetic analysis Plasmodium falciparum
Y528W substantial decrease in kcat value, decrease in FMN content. Pre-steady state kinetic analysis Plasmodium falciparum

Inhibitors

Inhibitors Comment Organism Structure
N-(3,5-dichloro-phenyl)-2-methyl-3-nitro-benzamide
-
Plasmodium falciparum

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
7.8
-
coenzyme Q1 mutant I272A, pH 8.0, 25°C Plasmodium falciparum
8.8
-
coenzyme QD mutant Y528A, pH 8.0, 25°C Plasmodium falciparum
11
-
coenzyme Q1 wild-type, pH 8.0, 25°C Plasmodium falciparum
12
-
coenzyme QD mutant I272A, pH 8.0, 25°C Plasmodium falciparum
13
-
coenzyme QD wild-type, pH 8.0, 25°C Plasmodium falciparum
15
-
coenzyme Q1 mutant F188A, pH 8.0, 25°C Plasmodium falciparum
16
-
coenzyme Q1 mutant F227A, pH 8.0, 25°C Plasmodium falciparum
16
-
coenzyme QD mutant L531A, pH 8.0, 25°C Plasmodium falciparum
16
-
coenzyme Q1 mutant Y528A, pH 8.0, 25°C Plasmodium falciparum
17
-
coenzyme Q1 mutant L531A, pH 8.0, 25°C Plasmodium falciparum
20
-
coenzyme QD mutant F188A, pH 8.0, 25°C Plasmodium falciparum
20
-
coenzyme QD mutant F227A, pH 8.0, 25°C Plasmodium falciparum
20
-
coenzyme Q1 mutant Y528F, pH 8.0, 25°C Plasmodium falciparum
22
-
coenzyme Q1 mutant H185A, pH 8.0, 25°C Plasmodium falciparum
26
-
coenzyme QD mutant R265A, pH 8.0, 25°C Plasmodium falciparum
34
-
coenzyme QD mutant H185A, pH 8.0, 25°C Plasmodium falciparum
38
-
coenzyme Q1 mutant R265A, pH 8.0, 25°C Plasmodium falciparum
45
-
coenzyme QD mutant Y528W, pH 8.0, 25°C Plasmodium falciparum
48
-
coenzyme Q1 mutant Y528W, pH 8.0, 25°C Plasmodium falciparum
53
-
coenzyme QD mutant Y528F, pH 8.0, 25°C Plasmodium falciparum

Localization

Localization Comment Organism GeneOntology No. Textmining

Organism

Organism UniProt Comment Textmining
Plasmodium falciparum Q08210
-
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
dihydroorotate + coenzyme Q1 coenzyme Q1 possesses a prenyl tail Plasmodium falciparum orotate + reduced coenzyme Q1
-
?
dihydroorotate + coenzyme QD coenzyme QD possesses a decyl tail Plasmodium falciparum orotate + reduced coenzyme QD
-
?
dihydroorotate + O2
-
Plasmodium falciparum orotate + H2O2
-
?

Turnover Number [1/s]

Turnover Number Minimum [1/s] Turnover Number Maximum [1/s] Substrate Comment Organism Structure
0.083
-
O2 mutant I272A, pH 8.0, 25°C Plasmodium falciparum
0.1
-
O2 mutant Y528A, pH 8.0, 25°C Plasmodium falciparum
0.12
-
coenzyme QD mutant Y528A, pH 8.0, 25°C Plasmodium falciparum
0.18
-
O2 mutant Y528W, pH 8.0, 25°C Plasmodium falciparum
0.19
-
coenzyme Q1 mutant Y528A, pH 8.0, 25°C Plasmodium falciparum
0.25
-
O2 mutant L531A, pH 8.0, 25°C Plasmodium falciparum
0.42
-
O2 wild-type, pH 8.0, 25°C Plasmodium falciparum
0.43
-
O2 mutant F227A, pH 8.0, 25°C Plasmodium falciparum
0.44
-
O2 mutant R265A, pH 8.0, 25°C Plasmodium falciparum
0.53
-
O2 mutant F188A, pH 8.0, 25°C Plasmodium falciparum
0.57
-
O2 mutant H185A, pH 8.0, 25°C Plasmodium falciparum
0.63
-
O2 mutant Y528F, pH 8.0, 25°C Plasmodium falciparum
1.2
-
coenzyme QD mutant Y528F, pH 8.0, 25°C Plasmodium falciparum
1.5
-
coenzyme Q1 mutant I272A, pH 8.0, 25°C Plasmodium falciparum
1.8
-
coenzyme QD mutant I272A, pH 8.0, 25°C Plasmodium falciparum
1.9
-
coenzyme Q1 mutant Y528F, pH 8.0, 25°C Plasmodium falciparum
2.6
-
coenzyme Q1 mutant F188A, pH 8.0, 25°C Plasmodium falciparum
2.6
-
coenzyme Q1 mutant F227A, pH 8.0, 25°C Plasmodium falciparum
3.1
-
coenzyme Q1 mutant R265A, pH 8.0, 25°C Plasmodium falciparum
3.5
-
coenzyme QD mutant F227A, pH 8.0, 25°C Plasmodium falciparum
4.3
-
coenzyme QD mutant F188A, pH 8.0, 25°C Plasmodium falciparum
5
-
coenzyme QD mutant R265A, pH 8.0, 25°C Plasmodium falciparum
5.1
-
coenzyme Q1 mutant L531A, pH 8.0, 25°C Plasmodium falciparum
5.1
-
coenzyme Q1 mutant Y528W, pH 8.0, 25°C Plasmodium falciparum
6.8
-
coenzyme QD mutant Y528W, pH 8.0, 25°C Plasmodium falciparum
7.3
-
coenzyme Q1 mutant H185A, pH 8.0, 25°C Plasmodium falciparum
7.8
-
coenzyme Q1 wild-type, pH 8.0, 25°C Plasmodium falciparum
7.9
-
coenzyme QD mutant H185A, pH 8.0, 25°C Plasmodium falciparum
8.6
-
coenzyme QD mutant L531A, pH 8.0, 25°C Plasmodium falciparum
12
-
coenzyme QD wild-type, pH 8.0, 25°C Plasmodium falciparum

IC50 Value

IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
0.049
-
wild-type, pH 8.0, 25°C Plasmodium falciparum N-(3,5-dichloro-phenyl)-2-methyl-3-nitro-benzamide
0.087
-
mutant L531A, pH 8.0, 25°C Plasmodium falciparum N-(3,5-dichloro-phenyl)-2-methyl-3-nitro-benzamide
0.1
-
mutant R265A, pH 8.0, 25°C Plasmodium falciparum N-(3,5-dichloro-phenyl)-2-methyl-3-nitro-benzamide
1.9
-
mutant F188A, pH 8.0, 25°C Plasmodium falciparum N-(3,5-dichloro-phenyl)-2-methyl-3-nitro-benzamide
2.9
-
mutant H185A, pH 8.0, 25°C Plasmodium falciparum N-(3,5-dichloro-phenyl)-2-methyl-3-nitro-benzamide
12
-
mutant F227A, pH 8.0, 25°C Plasmodium falciparum N-(3,5-dichloro-phenyl)-2-methyl-3-nitro-benzamide