Information on EC 1.3.5.2 - dihydroorotate dehydrogenase (quinone)

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The expected taxonomic range for this enzyme is: Eukaryota, Bacteria

EC NUMBER
COMMENTARY
1.3.5.2
-
RECOMMENDED NAME
GeneOntology No.
dihydroorotate dehydrogenase (quinone)
-
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
(S)-dihydroorotate + a quinone = orotate + a quinol
show the reaction diagram
different binding sites for dihydroorotate and the electron acceptor, two-site ping-pong mechanism. Cleavage site at R182 is conserved between the two major families of dihydroorotate dehydrogenases, it is positioned in a loop, which is crucial for catalysis but irrelevant for protein stability; ping-pong mechanism
-
(S)-dihydroorotate + a quinone = orotate + a quinol
show the reaction diagram
one-site ping-pong mechanism, residues 129-137 form a flexible loop, responsible for substrate binding
-
(S)-dihydroorotate + a quinone = orotate + a quinol
show the reaction diagram
existence of 3 families differing in their selectivity for oxidizing substrates: 1A are soluble, containing FMN and use fumarate, 1B are soluble, one subunit contains an iron-sulfur center, FAD and reduces NAD+, family 2 enzymes are membrane-bound, contain FMN and are oxidized by ubiquinone. Mechanism consists of 3 reaction phases. Different binding-mechanisms for enzyme the reaction-steps are suggested
-
(S)-dihydroorotate + a quinone = orotate + a quinol
show the reaction diagram
fourth step in biosynthesis of pyrimidines. Two domains: alpha/beta-barrel domain containing the active site, one alpha-helical domain that forms the opening of a tunnel leading to active site
-
(S)-dihydroorotate + a quinone = orotate + a quinol
show the reaction diagram
in liver, myocardium and skeletal muscle tissues the activity intensities vary from animal to animal, but are similar in ileum, colon and kidney cortex. Cardiac enzyme expresses a pronounced oxidase activity
-
(S)-dihydroorotate + a quinone = orotate + a quinol
show the reaction diagram
in liver, myocardium and skeletal muscle tissues the activity intensities vary from animal to animal, but are similar in ileum, colon and kidney cortex. Cardiac enzyme expresses a pronounced oxidase activity
(S)-dihydroorotate + a quinone = orotate + a quinol
show the reaction diagram
in liver, myocardium and skeletal muscle tissues the activity intensities vary from animal to animal, but are similar in ileum, colon and kidney cortex. Cardiac enzyme expresses a pronounced oxidase activity
-
(S)-dihydroorotate + a quinone = orotate + a quinol
show the reaction diagram
68% identity with type A enzyme of Lactococcus lactis, two-site non-classical ping-pong kinetic mechanism
-
(S)-dihydroorotate + a quinone = orotate + a quinol
show the reaction diagram
ping-pong mechanism; soluble quinones as second substrate
-
(S)-dihydroorotate + a quinone = orotate + a quinol
show the reaction diagram
ping-pong mechanism
-
(S)-dihydroorotate + a quinone = orotate + a quinol
show the reaction diagram
-
-
-
-
(S)-dihydroorotate + a quinone = orotate + a quinol
show the reaction diagram
two-site ping-pong mechanism
(S)-dihydroorotate + a quinone = orotate + a quinol
show the reaction diagram
enzyme uses a stepwise mechanism for dihydroorotate oxidation
(S)-dihydroorotate + a quinone = orotate + a quinol
show the reaction diagram
the active base S175 and the hydrogen bonding network including residues T178 and F115 work together for efficient deprotonation of dihydroorotate
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
oxidation
-
-
-
-
redox reaction
-
-
-
-
reduction
-
-
-
-
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
UMP biosynthesis
-
-
pyrimidine metabolism
-
-
Pyrimidine metabolism
-
-
Metabolic pathways
-
-
SYSTEMATIC NAME
IUBMB Comments
(S)-dihydroorotate:quinone oxidoreductase
This Class 2 dihydroorotate dehydrogenase enzyme contains FMN [4]. The enzyme is found in eukaryotes in the mitochondrial membrane, and in some Gram negative bacteria associated with the cytoplasmic membrane [2,5]. The reaction is the only redox reaction in the de-novo biosynthesis of pyrimidine nucleotides [2,4]. The best quinone electron acceptors for the enzyme from bovine liver are ubiquinone-6 and ubiquinone-7, although simple quinones, such as benzoquinone, can also act as acceptor at lower rates [2]. Methyl-, ethyl-, tert-butyl and benzyl (S)-dihydroorotates are also substrates, but methyl esters of (S)-1-methyl and (S)-3-methyl and (S)-1,3-dimethyldihydroorotates are not [2]. Class 1 dihydroorotate dehydrogenases use either fumarate (EC 1.3.98.1), NAD+ (EC 1.3.1.14) or NADP+ (EC 1.3.1.15) as electron acceptor.
SYNONYMS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
class 2 dihydroorotate dehydrogenases
-
-
DHO-DH
-
-
DHOD
-
-
DHODH
-
-
HsDHODH
-
-
L-5,6-dihydroorotate:ubiquinone exidoreductase
-
-
CAS REGISTRY NUMBER
COMMENTARY
59088-23-2
-
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
expression in Escherichia coli
-
-
Manually annotated by BRENDA team
; family 1 enzyme A
-
-
Manually annotated by BRENDA team
; family 2 enzyme
-
-
Manually annotated by BRENDA team
; recombinant protein
-
-
Manually annotated by BRENDA team
; truncated recombinant protein
-
-
Manually annotated by BRENDA team
; U937 membranes
-
-
Manually annotated by BRENDA team
recombinant protein
-
-
Manually annotated by BRENDA team
recombinant truncated enzyme
-
-
Manually annotated by BRENDA team
truncated recombinant protein
-
-
Manually annotated by BRENDA team
only enzyme A
-
-
Manually annotated by BRENDA team
; mature trophozytes and schizonts
-
-
Manually annotated by BRENDA team
expression in Escherichia coli
GenBank
Manually annotated by BRENDA team
; recombinant protein
-
-
Manually annotated by BRENDA team
; Wistar rats, both sexes, 6 month
Uniprot
Manually annotated by BRENDA team
recombinant protein
-
-
Manually annotated by BRENDA team
recombinant wild-type enzyme and N-terminally truncated form
-
-
Manually annotated by BRENDA team
tomato, cultured cells
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
metabolism
-
DHODH is the fourth enzyme in the biosynthesis of pyrimidines
physiological function
-
Plasmodium DHODH is an essential mitochondrial enzyme that catalyzes the flavin mononucleotide-dependent formation of orotic acid, a key step in de novo pyrimidine biosynthesis
physiological function
-
dihydroorotate dehydrogenase is associated with mitochondrial electron transport and required for de novo pyrimidine synthesis, and is required for N-(4-hydroxyphenyl)retinamide-induced reactive oxygen species production and apoptosis. Chemical inhibition of DHODH activity or the reduction of DHODH protein suppresses 4HPR-induced ROS production and apoptosis in transformed skin and prostate epithelial cells, overview
physiological function
-
the enzyme is involved in de novo biosynthesis of pyrimidines
physiological function
-
the enzyme is involved in de novo biosynthesis of pyrimidines, which is essential in malaria. Absence of pyrimidine salvage pathways in Plasmodium, thus the de novo pathway provides the only source of pyrimidines for cell growth. The mitochondrial enzyme requires oxidized ubiquinone, thus coupling pyrimidine biosynthesis to the respiratory chain
physiological function
-
DHODH catalyzes the rate-limiting step in the pyrimidine biosynthetic pathway
physiological function
-
the gene appears to be essential, because while gene tagging is successful at the TgDHOD gene locus, attempts to delete the TgDHOD gene were not successful in the KU80 background
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
(S)-dihydroorotate + 1,4-naphthoquinone
orotate + 1,4-naphthoquinol
show the reaction diagram
-
-
-
?
(S)-dihydroorotate + 2,3-dimethoxy-5-methyl-1,4-benzoquinone
orotate + 2,3-dimethoxy-5-methyl-1,4-benzoquinol
show the reaction diagram
-
-
-
?
(S)-dihydroorotate + 2,5-dimethyl-p-benzoquinone
orotate + 2,5-dimethyl-p-benzoquinol
show the reaction diagram
-
-
-
?
(S)-dihydroorotate + 2,6-dichlorophenolindophenol
orotate + reduced 2,6-dichlorophenolindophenol
show the reaction diagram
-
-
-
?
(S)-dihydroorotate + acceptor
orotate + reduced acceptor
show the reaction diagram
-
uses ubiquinone as electron acceptor
-
?
(S)-dihydroorotate + acceptor
orotate + reduced acceptor
show the reaction diagram
-
fumarate and menadione as electron acceptors
-
?
(S)-dihydroorotate + acceptor
orotate + reduced acceptor
show the reaction diagram
-
ubiquinone-6 tested as electron acceptor
-
?
(S)-dihydroorotate + acceptor
orotate + reduced acceptor
show the reaction diagram
-
with ubiquinone-0, 2,6-dichlorophenolindophenol, menadione, decylubiquinone, fumarate and O2 as electron acceptor
-
?
(S)-dihydroorotate + acceptor
orotate + reduced acceptor
show the reaction diagram
-
fourth step in synthesis of pyrimidine nucleotides
-
?
(S)-dihydroorotate + acceptor
orotate + reduced acceptor
show the reaction diagram
-
fourth step in synthesis of pyrimidine nucleotides
-
?
(S)-dihydroorotate + acceptor
orotate + reduced acceptor
show the reaction diagram
-
fourth step in synthesis of pyrimidine nucleotides
-
?
(S)-dihydroorotate + acceptor
orotate + reduced acceptor
show the reaction diagram
-
fourth step in synthesis of pyrimidine nucleotides
-
?
(S)-dihydroorotate + acceptor
orotate + reduced acceptor
show the reaction diagram
-
reduction of a number of substrates: fumatate, coenzyme ubiquinone-0 and menadione
-
?
(S)-dihydroorotate + decylubiquinone
orotate + decylubiquinol
show the reaction diagram
-
-
-
?
(S)-dihydroorotate + decylubiquinone
orotate + decylubiquinol
show the reaction diagram
-
-
-
?
(S)-dihydroorotate + oxidized 2,6-dichloroindophenol
orotate + reduced 2,6-dichloroindophenol
show the reaction diagram
-
-
-
?
(S)-dihydroorotate + ubiquinone
orotate + ubiquinol
show the reaction diagram
-
-
-
ir
(S)-dihydroorotate + ubiquinone
orotate + ubiquinol
show the reaction diagram
-
-
-
?
(S)-dihydroorotate + ubiquinone
orotate + ubiquinol
show the reaction diagram
-
-
-
?
(S)-dihydroorotate + ubiquinone
orotate + ubiquinol
show the reaction diagram
-
-
-
?
(S)-dihydroorotate + ubiquinone
orotate + ubiquinol
show the reaction diagram
-
-
-
(S)-dihydroorotate + ubiquinone
orotate + ubiquinol
show the reaction diagram
-
-
-
?
(S)-dihydroorotate + ubiquinone
orotate + ubiquinol
show the reaction diagram
-
-
-
?
(S)-dihydroorotate + ubiquinone
orotate + ubiquinol
show the reaction diagram
-
-
-
ir
(S)-dihydroorotate + ubiquinone
orotate + ubiquinol
show the reaction diagram
-
-
-
-
(S)-dihydroorotate + ubiquinone
orotate + ubiquinol
show the reaction diagram
-
-
-
-
(S)-dihydroorotate + ubiquinone
orotate + ubiquinol
show the reaction diagram
-
-
-
ir
(S)-dihydroorotate + ubiquinone
orotate + ubiquinol
show the reaction diagram
-
decylubiquinone as electron acceptor
-
?
(S)-dihydroorotate + ubiquinone
orotate + ubiquinol
show the reaction diagram
-
ubiquinone-6, ubiquinone-7, ubiquinone-9 and ubiquinone-10 maximize enzyme activity
-
-
(S)-dihydroorotate + ubiquinone
orotate + ubiquinol
show the reaction diagram
-
reaction studied with menadione, O2 and ferricyanide
-
?
(S)-dihydroorotate + ubiquinone
orotate + ubiquinol
show the reaction diagram
-
fourth enzyme in pyrimidine synthesis
-
?
(S)-dihydroorotate + ubiquinone
orotate + ubiquinol
show the reaction diagram
-
fourth enzyme in pyrimidine synthesis
-
ir
(S)-dihydroorotate + ubiquinone
orotate + ubiquinol
show the reaction diagram
-
fourth enzyme in pyrimidine synthesis
-
?
(S)-dihydroorotate + ubiquinone
orotate + ubiquinol
show the reaction diagram
-
fourth enzyme in pyrimidine synthesis
-
ir
(S)-dihydroorotate + ubiquinone
orotate + ubiquinol
show the reaction diagram
-
fourth enzyme in pyrimidine synthesis
-
?
(S)-dihydroorotate + ubiquinone
orotate + ubiquinol
show the reaction diagram
fourth enzyme in pyrimidine synthesis
-
ir
(S)-dihydroorotate + ubiquinone
orotate + ubiquinol
show the reaction diagram
-
six-step biosynthesis of pyrimidine uridine monophosphate
-
?
(S)-dihydroorotate + ubiquinone
orotate + ubiquinol
show the reaction diagram
-
fourth step in synthesis of uridine 5'-monophosphate
-
?
(S)-dihydroorotate + ubiquinone
orotate + ubiquinol
show the reaction diagram
-
fourth step in synthesis of uridine 5'-monophosphate
-
?
(S)-dihydroorotate + ubiquinone-30
orotate + ubiquinol-30
show the reaction diagram
-
-
-
?
(S)-dihydroorotate + ubiquinone-50
orotate + ubiquinol-50
show the reaction diagram
-
-
-
?
benzyl-(S)-dihydroorotate + acceptor
benzyl orotate + reduced acceptor
show the reaction diagram
-
-
-
?
dihydroorotate + 2,3-dimethoxy-5-methyl-1,4-benzoquinone
orotate + reduced 2,3-dimethoxy-5-methyl-1,4-benzoquinone
show the reaction diagram
-
-
?
dihydroorotate + 2,5-dimethyl-p-benzoquinone
orotate + reduced 2,5-dimethyl-p-benzoquinone
show the reaction diagram
95% the rate of decylubiquinone, wild-type, 75% the rate of decylubiquinone, DELTA1-75 mutant
-
?
dihydroorotate + 2,5-dimethylbenzoquinone
orotate + reduced 2,5-dimethylbenzoquinone
show the reaction diagram
-
84% of the rate with decylubiquinone
-
?
dihydroorotate + 2,6-dichloroindophenol
orotate + reduced 2,6-dichloroindophenol
show the reaction diagram
-
-
?
dihydroorotate + 2,6-dichlorophenolindophenol
orotate + reduced 2,6-dichlorophenolindophenol
show the reaction diagram
-
-
?
dihydroorotate + 2,6-dichlorophenolindophenol
orotate + reduced 2,6-dichlorophenolindophenol
show the reaction diagram
-
-
-
?
dihydroorotate + 2,6-dichlorophenolindophenol
orotate + reduced 2,6-dichlorophenolindophenol
show the reaction diagram
-
33% of the rate with decylubiquinone
-
?
dihydroorotate + acceptor
orotate + reduced acceptor
show the reaction diagram
-
-
-
?
dihydroorotate + acceptor
orotate + reduced acceptor
show the reaction diagram
-
-
-
?
dihydroorotate + acceptor
orotate + reduced acceptor
show the reaction diagram
-
-
-
?
dihydroorotate + acceptor
orotate + reduced acceptor
show the reaction diagram
-
-
-
?
dihydroorotate + acceptor
orotate + reduced acceptor
show the reaction diagram
-
-
-
?
dihydroorotate + acceptor
orotate + reduced acceptor
show the reaction diagram
-
-
-
?
dihydroorotate + acceptor
orotate + reduced acceptor
show the reaction diagram
-
-
-
?
dihydroorotate + acceptor
orotate + reduced acceptor
show the reaction diagram
-
-
-
dihydroorotate + acceptor
orotate + reduced acceptor
show the reaction diagram
-
-
?
dihydroorotate + acceptor
orotate + reduced acceptor
show the reaction diagram
-
-
-
?
dihydroorotate + acceptor
orotate + reduced acceptor
show the reaction diagram
-
-
-
?
dihydroorotate + acceptor
orotate + reduced acceptor
show the reaction diagram
-
-
?
dihydroorotate + acceptor
orotate + reduced acceptor
show the reaction diagram
-
acceptor: 2,6-dichlorophenolindophenol
-
?
dihydroorotate + acceptor
orotate + reduced acceptor
show the reaction diagram
-
acceptor: 2,6-dichlorophenolindophenol
-
?
dihydroorotate + acceptor
orotate + reduced acceptor
show the reaction diagram
-
acceptor: 2,6-dichlorophenolindophenol
-
?
dihydroorotate + acceptor
orotate + reduced acceptor
show the reaction diagram
-
acceptors: e.g. phenazine methosulfate
-
?
dihydroorotate + acceptor
orotate + reduced acceptor
show the reaction diagram
-
acceptor: menaquinone
-
?
dihydroorotate + acceptor
orotate + reduced acceptor
show the reaction diagram
-
acceptor: quinones
-
?
dihydroorotate + acceptor
orotate + reduced acceptor
show the reaction diagram
-
acceptor: quinones
-
?
dihydroorotate + acceptor
orotate + reduced acceptor
show the reaction diagram
-
acceptor: quinones
-
-
dihydroorotate + acceptor
orotate + reduced acceptor
show the reaction diagram
-
acceptor: coenzyme Q6
-
?
dihydroorotate + acceptor
orotate + reduced acceptor
show the reaction diagram
-
acceptor: coenzyme Q6
-
?
dihydroorotate + acceptor
orotate + reduced acceptor
show the reaction diagram
-
not acceptor: oxygen
-
?
dihydroorotate + acceptor
orotate + reduced acceptor
show the reaction diagram
-
not acceptor: oxygen, cytochrome b, cytochrome c, pyridine nucleotides (NAD+, NADP+) cannot serve as electron acceptors
-
?
dihydroorotate + acceptor
orotate + reduced acceptor
show the reaction diagram
-
acceptor: menadione
-
?
dihydroorotate + acceptor
orotate + reduced acceptor
show the reaction diagram
-
acceptor: menadione
-
-
dihydroorotate + acceptor
orotate + reduced acceptor
show the reaction diagram
-
acceptor (low activity): 1,4-naphthoquinone, 5,8-hydroxy-naphthoquinone, juglon, plumbagin, polyporic acid
-
?
dihydroorotate + acceptor
orotate + reduced acceptor
show the reaction diagram
-
acceptor: ubiquinone
-
?
dihydroorotate + acceptor
orotate + reduced acceptor
show the reaction diagram
-
acceptor: ubiquinone
-
-
dihydroorotate + acceptor
orotate + reduced acceptor
show the reaction diagram
-
acceptor: ubiquinone
-
?
dihydroorotate + acceptor
orotate + reduced acceptor
show the reaction diagram
-
acceptor: ubiquinone
-
?
dihydroorotate + acceptor
orotate + reduced acceptor
show the reaction diagram
-
acceptor: oxygen, slowly
-
?
dihydroorotate + acceptor
orotate + reduced acceptor
show the reaction diagram
-
acceptor coenzyme Q7
-
?
dihydroorotate + acceptor
orotate + reduced acceptor
show the reaction diagram
-
acceptor: fumarate, coenzyme Q10
-
-
dihydroorotate + acceptor
orotate + reduced acceptor
show the reaction diagram
-
reaction intermediates, mechanism, pH-dependence of reaction
-
-
dihydroorotate + acceptor
orotate + reduced acceptor
show the reaction diagram
-
mechanism and pH-dependence of reaction
-
-
dihydroorotate + acceptor
orotate + reduced acceptor
show the reaction diagram
-
physiological electron acceptor: ubiquinone (aerobic conditions), menaquinone (anaerobic conditions)
-
?
dihydroorotate + acceptor
orotate + reduced acceptor
show the reaction diagram
-
fourth step in pyrimidine biosynthesis
-
?
dihydroorotate + coenzyme Q
orotate + reduced coenzyme Q
show the reaction diagram
-
coenzyme OD possesses a decyl tail
-
?
dihydroorotate + coenzyme Q1
orotate + reduced coenzyme Q1
show the reaction diagram
-
coenzyme Q1 possesses a prenyl tail
-
?
dihydroorotate + coenzyme QD
orotate + reduced coenzyme QD
show the reaction diagram
-
coenzyme QD possesses a decyl tail
-
?
dihydroorotate + CoQ0
orotate + reduced CoQo
show the reaction diagram
102% the rate of decylubiquinone, wild-type, 67% the rate of decylubiquinone, DELTA1-75 mutant
-
?
dihydroorotate + decylplastoquinone
orotate + reduced decylplastoquinone
show the reaction diagram
-
78% of the rate with decylubiquinone
-
?
dihydroorotate + decylplastoquinone
orotate + reduced decylplastoquinone
show the reaction diagram
95% the rate of decylubiquinone, wild-type, 104% the rate of decylubiquinone, DELTA1-75 mutant
-
?
dihydroorotate + decylubiquinone
orotate + reduced decylubiquinone
show the reaction diagram
-
-
-
?
dihydroorotate + decylubiquinone
orotate + reduced decylubiquinone
show the reaction diagram
-
-
?
dihydroorotate + decylubiquinone
orotate + reduced decylubiquinone
show the reaction diagram
-
-
?
dihydroorotate + menadione
orotate + reduced menadione
show the reaction diagram
-
39% of the rate with decylubiquinone
-
?
dihydroorotate + menadione
orotate + reduced menadione
show the reaction diagram
82% the rate of decylubiquinone, wild-type, 78% the rate of decylubiquinone, DELTA1-75 mutant
-
?
dihydroorotate + O2
orotate + H2O2
show the reaction diagram
-
-
-
?
dihydroorotate + potassium hexacyanoferrate(III)
orotate + reduced potassium hexacyanoferrate(III)
show the reaction diagram
-
-
?
dihydroorotate + ubiquinone 30
orotate + reduced ubiquinone 30
show the reaction diagram
-
-
?
dihydroorotate + ubiquinone 50
orotate + reduced ubiquinone 50
show the reaction diagram
-
-
?
dihydroorotate + ubiquinone-0
orotate + reduced ubiquinone-0
show the reaction diagram
-
80% of the rate with decylubiquinone
-
?
dihydroorotate + ubiquinone-10
orotate + reduced ubiquinone-10
show the reaction diagram
-
59% of the rate with decylubiquinone
-
?
dihydroorotate + ubiquinone-50
orotate + reduced ubiquinone-50
show the reaction diagram
83% the rate of decylubiquinone, wild-type, 76% the rate of decylubiquinone, DELTA1-75 mutant
-
?
ethyl-dihydroorotate + acceptor
ethyl-orotate + reduced acceptor
show the reaction diagram
-
-
-
?
L-dihydroorotate + 2,6-dichloroindophenol
orotate + ?
show the reaction diagram
-
-
-
?
L-dihydroorotate + 2,6-dichlorophenolindophenol
orotate + reduced 2,6-dichlorophenolindophenol
show the reaction diagram
-
-
-
-
L-dihydroorotate + 2,6-dichlorophenolindophenol
orotate + reduced 2,6-dichlorophenolindophenol
show the reaction diagram
-
-
-
?
L-dihydroorotate + decylubiquinone
orotate + ?
show the reaction diagram
-
-
-
?
L-dihydroorotate + decylubiquinone
orotate + reduced decylubiquinone
show the reaction diagram
-
-
-
-
L-dihydroorotate + decylubiquinone
orotate + reduced decylubiquinone
show the reaction diagram
-
-
-
-
L-dihydroorotate + decylubiquinone
orotate + reduced decylubiquinone
show the reaction diagram
-
-
-
?
L-dihydroorotate + decylubiquinone
orotate + reduced decylubiquinone
show the reaction diagram
-
-
?
L-dihydroorotate + decylubiquinone
orotate + reduced decylubiquinone
show the reaction diagram
-
-
?
L-dihydroorotate + FMN
orotate + FMNH2
show the reaction diagram
-
-
-
?
L-dihydroorotate + FMN
orotate + FMNH2
show the reaction diagram
-
-
-
?
L-dihydroorotate + FMN
orotate + FMNH2
show the reaction diagram
-
-
-
?
L-dihydroorotate + FMN
orotate + FMNH2
show the reaction diagram
-
-
-
?
L-dihydroorotate + FMN
orotate + FMNH2
show the reaction diagram
-
DHODH catalyzes the FMN-dependent oxidation of dihydroorotate to produce orotic acid. Two separate half reactions are required to complete the catalytic cycle: 1. oxidation of dihydroorotate driven by the reduction of FMN and, 2. reoxidation of FMNH2 to regenerate the active enzyme
-
?
L-dihydroorotate + ubiquinone-0
orotate + reduced ubiquinone-0
show the reaction diagram
-
-
?
L-dihydroorotate + ubiquinone-4
orotate + reduced ubiquinone-4
show the reaction diagram
-
-
?
L-dihydroorotate + ubiquinone-6
orotate + reduced ubiquinone-6
show the reaction diagram
-
-
-
-
L-dihydroorotate + ubiquinone-6
orotate + reduced ubiquinone-6
show the reaction diagram
-
-
-
-
L-dihydroorotate + ubiquinone-6
orotate + reduced ubiquinone-6
show the reaction diagram
-
-
-
-
L-dihydroorotate + ubiquinone-6
orotate + reduced ubiquinone-6
show the reaction diagram
-
-
-
-
L-dihydroorotate + ubiquinone-6
orotate + reduced ubiquinone-6
show the reaction diagram
-
-
?
L-dihydroorotate + vitamin K3
orotate + reduced vitamin K3
show the reaction diagram
-
-
?
methyl-dihydroorotate + acceptor
methyl-orotate + reduced acceptor
show the reaction diagram
-
-
-
?
tert-butyl-dihydroorotate + acceptor
tert-butyl-orotate + reduced acceptor
show the reaction diagram
-
-
-
?
methyl-dihydroorotate + acceptor
methyl-orotate + reduced acceptor
show the reaction diagram
-
-
-
?
additional information
?
-
-
not substrate: 1-methyl-(S)-dihydroorotate, 3-methyl-dihydroorotate, 1,3-dimethyldihydroorotate
-
-
-
additional information
?
-
-
enzyme has methylviologen-fumarate reductase activity
-
-
-
additional information
?
-
-
computational method to investigate potential proton relay pathways in the active site of the enzyme
-
-
-
additional information
?
-
fumarate and NAD are inadequate electron acceptors for full-length DHODH and N-terminally truncated DHODH
-
-
-
additional information
?
-
-
fumarate is a poor electron acceptor
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
(S)-dihydroorotate + acceptor
orotate + reduced acceptor
show the reaction diagram
-
fourth step in synthesis of pyrimidine nucleotides
-
?
(S)-dihydroorotate + acceptor
orotate + reduced acceptor
show the reaction diagram
-
fourth step in synthesis of pyrimidine nucleotides
-
?
(S)-dihydroorotate + acceptor
orotate + reduced acceptor
show the reaction diagram
-
fourth step in synthesis of pyrimidine nucleotides
-
?
(S)-dihydroorotate + acceptor
orotate + reduced acceptor
show the reaction diagram
-
fourth step in synthesis of pyrimidine nucleotides
-
?
(S)-dihydroorotate + acceptor
orotate + reduced acceptor
show the reaction diagram
-
reduction of a number of substrates: fumatate, coenzyme ubiquinone-0 and menadione
-
?
(S)-dihydroorotate + ubiquinone
orotate + ubiquinol
show the reaction diagram
-
-
-
ir
(S)-dihydroorotate + ubiquinone
orotate + ubiquinol
show the reaction diagram
-
fourth enzyme in pyrimidine synthesis
-
?
(S)-dihydroorotate + ubiquinone
orotate + ubiquinol
show the reaction diagram
-
fourth enzyme in pyrimidine synthesis
-
ir
(S)-dihydroorotate + ubiquinone
orotate + ubiquinol
show the reaction diagram
-
fourth enzyme in pyrimidine synthesis
-
?
(S)-dihydroorotate + ubiquinone
orotate + ubiquinol
show the reaction diagram
-
fourth enzyme in pyrimidine synthesis
-
ir
(S)-dihydroorotate + ubiquinone
orotate + ubiquinol
show the reaction diagram
-
fourth enzyme in pyrimidine synthesis
-
?
(S)-dihydroorotate + ubiquinone
orotate + ubiquinol
show the reaction diagram
Q63707
fourth enzyme in pyrimidine synthesis
-
ir
(S)-dihydroorotate + ubiquinone
orotate + ubiquinol
show the reaction diagram
-
six-step biosynthesis of pyrimidine uridine monophosphate
-
?
(S)-dihydroorotate + ubiquinone
orotate + ubiquinol
show the reaction diagram
-
fourth step in synthesis of uridine 5'-monophosphate
-
?
(S)-dihydroorotate + ubiquinone
orotate + ubiquinol
show the reaction diagram
-
fourth step in synthesis of uridine 5'-monophosphate
-
?
dihydroorotate + acceptor
orotate + reduced acceptor
show the reaction diagram
-
-
-
?
dihydroorotate + acceptor
orotate + reduced acceptor
show the reaction diagram
-
physiological electron acceptor: ubiquinone (aerobic conditions), menaquinone (anaerobic conditions)
-
?
dihydroorotate + acceptor
orotate + reduced acceptor
show the reaction diagram
-
fourth step in pyrimidine biosynthesis
-
?
L-dihydroorotate + FMN
orotate + FMNH2
show the reaction diagram
-
-
-
?
L-dihydroorotate + FMN
orotate + FMNH2
show the reaction diagram
-
-
-
?
L-dihydroorotate + FMN
orotate + FMNH2
show the reaction diagram
-
-
-
?
L-dihydroorotate + FMN
orotate + FMNH2
show the reaction diagram
-
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
2-methyl-1,4-naphthoquinone
little catalytic efficiency, N-terminally truncated protein
flavin
-
enzyme contains flavin
flavin
0.8-1.1 mol per mol of protein
FMN
-
tightly bound
FMN
-
0.5-0.8 mol/mol
FMN
-
0.8-1.1 mol/mol
FMN
-
; flavoprotein
FMN
-
does not contain FMN
FMN
-
1 mol of FMN per 120000 g of active enzyme
FMN
-
-
FMN
0.9 molar equivalents, N-terminally truncated protein
FMN
-
Lys100 and Lys225 enhance the structural stability of the active site by hydrogen bonding to the FMN cofactor
FMN
-
dependent on
ubiquinone
-
the mitochondrial enzyme requires oxidized ubiquinone, CoQ
ubiquinone-0
little catalytic efficiency, N-terminally truncated protein
Ubiquinone-10
CoQD, efficient, N-terminally truncated protein
ubiquinone-4
efficient, N-terminally truncated protein
ubiquinone-8
efficient, N-terminally truncated protein
FMN
-
class 2 mitochondrial enzyme
additional information
-
flavin-containing
-
additional information
-
does not contain a flavin cofactor
-
additional information
-
flavoenzyme, 0.6-1.2 mol flavin per mol protein
-
additional information
-
enzyme does not contain FAD, FMN, covalently bound flavin or ubiquinone
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Iron
-
iron-zinc protein
Iron
-
1.4 mol of ferric iron per 120000 g of active enzyme
Iron
-
iron-sulfur center
Zinc
-
iron-zinc protein
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(2,3-difluoro-phenyl)-(5-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-yl)-amine
-
-
-
(2,5-difluoro-phenyl)-(5-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-yl)-amine
-
-
-
(2,6-difluoro-phenyl)-(5-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-yl)-amine
-
-
-
(2-chloro-phenyl)-(5-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-yl)-amine
-
-
-
(2-fluoro-4-methyl-phenyl)-(5-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-yl)-amine
-
-
-
(2E)-2-cyano-3-hydroxy-N-[4-(trifluoromethyl)phenyl]but-2-enamide
-
50% inhibition at 0.000435 mM
(2Z)-2-cyano-3-cyclopropyl-3-hydroxy-N-[4-(trifluoromethyl)phenyl]prop-2-enamide
-
inhibitor based on the active metabolite of the anti-inflammatory drug leflunomide. Comparison of inhibitory effect and binding to human and Plasmodium falciparum enzyme
-
(2Z)-2-cyano-N-(2',3-dichlorobiphenyl-4-yl)-3-hydroxybut-2-enamide
-
inhibitor based on the active metabolite of the anti-inflammatory drug leflunomide. Comparison of inhibitory effect and binding to human and Plasmodium falciparum enzyme
-
(2Z)-2-cyano-N-(2,2'-dichlorobiphenyl-4-yl)-3-hydroxybut-2-enamide
-
inhibitor based on the active metabolite of the anti-inflammatory drug leflunomide. Comparison of inhibitory effect and binding to human and Plasmodium falciparum enzyme
-
(2Z)-2-cyano-N-(2,3'-dichlorobiphenyl-4-yl)-3-hydroxybut-2-enamide
-
inhibitor based on the active metabolite of the anti-inflammatory drug leflunomide. Comparison of inhibitory effect and binding to human and Plasmodium falciparum enzyme
-
(2Z)-2-cyano-N-(3'-ethoxybiphenyl-4-yl)-3-hydroxybut-2-enamide
-
inhibitor based on the active metabolite of the anti-inflammatory drug leflunomide. Comparison of inhibitory effect and binding to human and Plasmodium falciparum enzyme
-
(2Z)-N-(2'-chlorobiphenyl-4-yl)-2-cyano-3-hydroxybut-2-enamide
-
inhibitor based on the active metabolite of the anti-inflammatory drug leflunomide. Comparison of inhibitory effect and binding to human and Plasmodium falciparum enzyme
-
(2Z)-N-(3-chloro-2'-methoxybiphenyl-4-yl)-2-cyano-3-hydroxybut-2-enamide
-
inhibitor based on the active metabolite of the anti-inflammatory drug leflunomide. Comparison of inhibitory effect and binding to human and Plasmodium falciparum enzyme
-
(2Z)-N-(biphenyl-4-yl)-2-cyano-3-hydroxybut-2-enamide
-
inhibitor based on the active metabolite of the anti-inflammatory drug leflunomide. Comparison of inhibitory effect and binding to human and Plasmodium falciparum enzyme
-
(2Z)-N-[2'-chloro-3-(trifluoromethyl)biphenyl-4-yl]-2-cyano-3-hydroxybut-2-enamide
-
inhibitor based on the active metabolite of the anti-inflammatory drug leflunomide. Comparison of inhibitory effect and binding to human and Plasmodium falciparum enzyme
-
(3,4-difluoro-phenyl)-(5-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-yl)-amine
-
-
-
(3,4-dimethyl-phenyl)-(5-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-yl)-amine
-
-
-
(3,5-bis-trifluoromethyl-phenyl)-(5-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-yl)-amine
-
-
-
(3,5-difluoro-phenyl)-(5-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-yl)-amine
-
-
-
(3-chloro-phenyl)-(5-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-yl)-amine
-
-
-
(3-fluoro-4-methyl-phenyl)-(5-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-yl)-amine
-
-
-
(3-fluoro-4-trifluoromethyl-phenyl)-(5-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-yl)-amine
-
-
-
(3-fluoro-phenyl)-(5-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-yl)-amine
-
-
-
(4-benzyl-phenyl)-(5-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-yl)-amine
-
-
-
(4-bromo-3-trifluoromethyl-phenyl)-(5-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-yl)-amine
-
-
-
(4-bromo-phenyl)-(5-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-yl)-amine
-
-
-
(4-chloro-3-trifluoromethyl-phenyl)-(5-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-yl)-amine
-
-
-
(4-chloro-phenyl)-(5-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-yl)-amine
-
-
-
(4-difluoromethoxy-phenyl)-(5-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-yl)-amine
-
-
-
(4-fluoro-3-methyl-phenyl)-(5-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-yl)-amine
-
-
-
(4-fluoro-phenyl)-(5-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-yl)-amine
-
-
-
(4-methoxy-phenyl)(5-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-yl)-amine
-
-
-
(5-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-yl)-(2,3,4,5,6-pentafluorophenyl)-amine
-
-
-
(5-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-yl)-(2,3,4-trifluoro-phenyl)-amine
-
-
-
(5-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-yl)-(2,3,5,6-tetrafluoro-phenyl)-amine
-
-
-
(5-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-yl)-(2,4,5-trifluoro-phenyl)-amine
-
-
-
(5-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-yl)-(2,4,6-trifluoro-phenyl)-amine
-
-
-
(5-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-yl)-(2-trifluoromethyl-phenyl)-amine
-
-
-
(5-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-yl)-(3-trifluoromethyl-phenyl)-amine
-
-
-
(5-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-yl)-(4-methyl-3-trifluoromethylphenyl)-amine
-
-
-
(5-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-yl)-(4-nitro-phenyl)-amine
-
-
-
(5-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-yl)-(4-trifluoromethoxy-phenyl)-amine
-
-
-
(5-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-yl)-(4-trifluoromethyl-phenyl)-amine
-
DSM74
-
(5-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-yl)-m-tolyl-amine
-
-
-
(5-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-yl)-naphthalen-2-yl-amine
-
DSM1, a potent triazolopyrimidine-based inhibitor of PfDHODH that shows greater than 4000fold selectivity for the malarial enzyme when compared to human DHODH
-
(5-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-yl)-o-tolyl-amine
-
-
-
(5-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-yl)-p-tolyl-amine
-
-
-
(R)-dihydroorotate
-
-
1,10-phenanthroline
-
-
1-(1-naphthyl)-3-[2-(trifluoromethyl)phenyl]urea
-
50% inhibition at 0.0004 mM, wild type, 0.00034 mM, mutant R265A, above 0.2, mutant H185A
1-(2-methoxyphenyl)-3-(1-naphthyl)urea
-
50% inhibition at 0.00023 mM, wild type, 0.00024 mM, mutant R265A, 0.140, mutant H185A
1-(2-methoxyphenyl)-3-naphthalen-1-ylurea
-
-
1-(4-chlorophenyl)-3-quinolin-8-ylurea
-
50% inhibition at 0.00078 mM, wild type, 0.002 mM, mutant R265A, above 0.4, mutant H185A
1-hydroxy-2-dodecyl-4(1)quinolone
-
competitive with regard to decylubiquinone, uncompetitive with regard to dihydroorotate
-
2-(4'-tert-butyl-2-chloro-biphenyl-4-ylcarbamoyl)-cyclopent-1-enecarboxylic acid
-
50% inhibition at 0.000080 mM
2-(5-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-ylamino)-benzonitrile
-
-
-
2-([[2,3,5,6-tetrafluoro-3'-(trifluoromethoxy)biphenyl-4-yl]amino]carbonyl)cyclopent-1-ene-1-carboxylic acid
-
50% inhibition at 0.000007 mM
2-([[2-chloro-3'-(trifluoromethoxy)biphenyl-4-yl]amino]carbonyl)cyclopent-1-ene-1-carboxylic acid
-
50% inhibition at 0.000020 mM
2-([[2-chloro-4'-(dimethylamino)biphenyl-4-yl]amino]carbonyl)cyclopent-1-ene-1-carboxylic acid
-
50% inhibition at 0.00005 mM
2-([[3'-(trifluoromethoxy)-3-(trifluoromethyl)biphenyl-4-yl]amino]carbonyl)cyclopent-1-ene-1-carboxylic acid
-
50% inhibition at 0.000840 mM
2-([[3,5-difluoro-3'-(trifluoromethoxy)biphenyl-4-yl]amino]carbonyl)cyclopent-1-ene-1-carboxylic acid
-
50% inhibition at 0.000033 mM
2-([[3-chloro-3'-(trifluoromethoxy)biphenyl-4-yl]amino]carbonyl)cyclopent-1-ene-1-carboxylic acid
-
50% inhibition at 0.000290 mM
2-([[3-cyano-3'-(trifluoromethoxy)biphenyl-4-yl]amino]carbonyl)cyclopent-1-ene-1-carboxylic acid
-
50% inhibition at 0.000370 mM
2-([[3-fluoro-3'-(trifluoromethoxy)biphenyl-4-yl]amino]carbonyl)cyclopent-1-ene-1-carboxylic acid
-
50% inhibition at 0.00028 mM
2-([[3-fluoro-4'-(trifluoromethoxy)biphenyl-4-yl]amino]carbonyl)cyclopent-1-ene-1-carboxylic acid
-
50% inhibition at 0.00570 mM
2-([[3-methyl-3'-(trifluoromethoxy)biphenyl-4-yl]amino]carbonyl)cyclopent-1-ene-1-carboxylic acid
-
50% inhibition at 0.000150 mM
2-([[3-nitro-3'-(trifluoromethoxy)biphenyl-4-yl]amino]carbonyl)cyclopent-1-ene-1-carboxylic acid
-
50% inhibition at 0.000390 mM
2-([[4'-(dimethylamino)-3,5-difluorobiphenyl-4-yl]amino]carbonyl)cyclopent-1-ene-1-carboxylic acid
-
50% inhibition at 0.00061 mM
2-([[4-(1-naphthyl)-2-(trifluoromethyl)phenyl]amino]carbonyl)cyclopent-1-ene-1-carboxylic acid
-
50% inhibition at 0.000180 mM
2-cyano-3-(9-ethyl-9H-carbazol-3-ylamino)acrylic acid ethyl ester
-
IC50: 0.491 mM
2-cyano-3-(9-ethyl-9H-carbazol-3-ylamino)acrylic acid ethyl ester
-
IC50: 0.00044 mM
2-cyano-3-cyclopropyl-3-hydroxy-N-[4'-(cyano)phenyl]-propenamide
-
50% inhibition at 0.0.00035 mM, N-terminally truncated protein
2-cyano-3-cyclopropyl-3-hydroxy-N-[4'-(cyano)phenyl]-propenamide
50% inhibition at 0.712 mM, N-terminally truncated protein
2-cyano-3-cyclopropyl-3-hydroxy-N-[4'-(nitro)phenyl]-propenamide
-
50% inhibition at 0.00025 mM, N-terminally truncated protein
2-cyano-3-cyclopropyl-3-hydroxy-N-[4'-(nitro)phenyl]-propenamide
50% inhibition at 0.543 mM, N-terminally truncated protein
2-cyano-3-cyclopropyl-3-hydroxy-N-[4'-(trifluoromethyl)phenyl]-propenamide
-
50% inhibition at 0.00019 mM, N-terminally truncated protein
2-cyano-3-cyclopropyl-3-hydroxy-N-[4'-(trifluoromethyl)phenyl]-propenamide
50% inhibition at 1.08 mM, N-terminally truncated protein
2-cyano-3-hydroxy-N-(2',3,3'-trichlorobiphenyl-4-yl)but-2-enamide
-
-
-
2-hydroxyethylidene-cyano acetic acid 4-trifluoromethyl anilide
-
A177-1726, active derivative of human inhibitor leflunomide
2-hydroxyethylidene-cyanoacetic acid 4-trifluoromethyl anilide
-
anti-proliferative effect of A77 1726 is mediated by inhibition of enzyme
2-hydroxyethylidene-cyanoacetic acid 4-trifluoromethyl anilide
-
inbibits by interference with the transfer of electrons from flavin to quinone
2-hydroxyethylidene-cyanoacetic acid 4-trifluoromethyl anilide
-
A77 1726, active metabolite of leflumonide
2-hydroxyethylidene-cyanoacetic acid 4-trifluoromethyl anilide
-
noncompetitive versus ubiquinone, uncompetitive versus dihydroorotate, study of kinetics
2-methyl-3-nitro-N-[3-(trifluoromethyl)phenyl]benzamide
-
50% inhibition at 0.00008 mM, wild type, 0.00037 mM, mutant R265A, 0.120, mutant H185A
2-methyl-N-1-naphthyl-3-nitrobenzamide
-
50% inhibition at 0.00008 mM, wild type, 0.00048 mM, mutant R265A, 0.180, mutant H185A
2-[(2,5-dichlorophenyl)sulfanyl]-5-ethyl[1,2,4]triazolo[1,5-a]pyrimidin-7-ol
-
compound has therapeutically relevant activity against human enzyme
2-[(2,5-dichlorophenyl)sulfanyl]-5-ethyl[1,2,4]triazolo[1,5-a]pyrimidin-7-ol
-
no specific inhibition of Plasmodium enzyme, good inhibitor of human enzyme
2-[(2,5-dichlorophenyl)sulfanyl]-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-7-ol
-
compound has therapeutically relevant activity against human enzyme
2-[(2,5-dichlorophenyl)sulfanyl]-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-7-ol
-
no specific inhibition of Plasmodium enzyme, good inhibitor of human enzyme
2-[(3,4-dichlorophenyl)sulfanyl]-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-7-ol
-
compound is less active with human enzyme but good inhibitor of Plasmodium falciparum enzyme
2-[(3,4-dichlorophenyl)sulfanyl]-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-7-ol
-
-
2-[(4-chlorophenyl)sulfanyl]-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-7-ol
-
compound is less active with human enzyme but good inhibitor of Plasmodium falciparum enzyme
2-[(4-chlorophenyl)sulfanyl]-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-7-ol
-
-
2-[(biphenyl-4-ylamino)carbonyl]cyclopent-1-ene-1-carboxylic acid
-
50% inhibition at 0.00041 mM
2-[(E)-2-(2-methylphenyl)ethenyl]quinolin-4-ol
-
-
2-[[(2',3,5-trifluorobiphenyl-4-yl)amino]carbonyl]cyclopent-1-ene-1-carboxylic acid
-
50% inhibition at 0.000045 mM
2-[[(2'-chloro-3,5-difluorobiphenyl-4-yl)amino]carbonyl]cyclopent-1-ene-1-carboxylic acid
-
50% inhibition at 0.000018 mM
2-[[(2'-chlorobiphenyl-4-yl)amino]carbonyl]cyclopent-1-ene-1-carboxylic acid
-
50% inhibition at 0.000225 mM
2-[[(2,3,5,6-tetrafluoro-2'-methoxybiphenyl-4-yl)amino]carbonyl]cyclopent-1-ene-1-carboxylic acid
-
50% inhibition at 0.000008 mM
2-[[(3'-ethoxy-3,5-difluorobiphenyl-4-yl)amino]carbonyl]cyclopent-1-ene-1-carboxylic acid
-
50% inhibition at 0.000017 mM
2-[[(3,3'-dimethoxybiphenyl-4-yl)amino]carbonyl]cyclopent-1-ene-1-carboxylic acid
-
50% inhibition at 0.000170 mM
2-[[(3,5-difluoro-2',4'-dimethoxybiphenyl-4-yl)amino]carbonyl]cyclopent-1-ene-1-carboxylic acid
-
50% inhibition at 0.000090 mM
2-[[(3,5-difluoro-2'-methoxybiphenyl-4-yl)amino]carbonyl]cyclopent-1-ene-1-carboxylic acid
-
50% inhibition at 0.000042 mM
2-[[(3-chloro-2'-methoxybiphenyl-4-yl)amino]carbonyl]cyclopent-1-ene-1-carboxylic acid
-
50% inhibition at 0.000310 mM
2-[[(3-chloro-4'-methoxybiphenyl-4-yl)amino]carbonyl]cyclopent-1-ene-1-carboxylic acid
-
50% inhibition at 0.00840 mM
2-[[(3-fluoro-3'-hydroxybiphenyl-4-yl)amino]carbonyl]cyclopent-1-ene-1-carboxylic acid
-
50% inhibition at 0.000610 mM
-
2-[[(3-fluoro-4'-methoxybiphenyl-4-yl)amino]carbonyl]cyclopent-1-ene-1-carboxylic acid
-
50% inhibition at 0.00170 mM
2-[[(4'-bromo-2-chlorobiphenyl-4-yl)amino]carbonyl]cyclopent-1-ene-1-carboxylic acid
-
50% inhibition at 0.000070 mM
2-[[(4'-bromo-3-chlorobiphenyl-4-yl)amino]carbonyl]cyclopent-1-ene-1-carboxylic acid
-
50% inhibition at 0.002900 mM
2-[[(4'-bromo-3-fluorobiphenyl-4-yl)amino]carbonyl]cyclopent-1-ene-1-carboxylic acid
-
50% inhibition at 0.000735 mM
3-hydroxy-2-(3,3-dichloroallyl)-1,4-naphthoquinone
-
50% inhibition at 0.000065 mM, i. e. dichloroallyl lawsone, N-terminally truncated protein
3-hydroxy-2-(3,3-dichloroallyl)-1,4-naphthoquinone
50% inhibition at 0.220 mM, i. e. dichloroallyl lawsone, N-terminally truncated protein
4-(5-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-ylamino)-2-trifluoromethylbenzonitrile
-
-
-
4-pentyl-1,3,4,10-tetrahydroacridin-9(2H)-one
-
-
4-pentyl-1,3,4,10-tetrahydroacridin-9(2H)-one
-
-
4-pentyl-1,3,4,10-tetrahydroacridin-9(2H)-one
-
-
4-[(5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-7-yl)amino]-2-(trifluoromethyl)benzonitrile
-
-
5,6-dimethyl-N-(naphthalen-2-yl)[1,2,4]triazolo[1,5-a]pyrimidin-7-amine
-
-
5-(1H-benzimidazol-1-yl)-N-propylthiophene-2-carboxamide
-
-
5-(1H-indol-1-yl)-N-propylthiophene-2-carboxamide
-
-
5-(2-methyl-1H-benzimidazol-1-yl)-N-propylthiophene-2-carboxamide
-
-
5-(2-methyl-1H-indol-1-yl)-N-propylthiophene-2-carboxamide
-
-
5-(2-methyl-1H-indol-1-yl)-N-propylthiophene-2-carboxamide
-
-
5-(2-methyl-1H-indol-1-yl)-N-propylthiophene-2-carboxamide
-
-
5-(4-methylpiperazin-1-yl)-N-propylthiophene-2-carboxamide
-
-
5-(piperidin-1-yl)-N-propylthiophene-2-carboxamide
-
-
5-aminoorotate
-
-
5-bromoorotate
-
-
5-ethyl-N-(naphthalen-2-yl)[1,2,4]triazolo[1,5-a]pyrimidin-7-amine
-
-
5-Fluoroorotate
-
-
5-iodoorotate
-
-
5-methoxy-2-[(4-phenoxyphenyl)amino]benzoic acid
-
-
5-methyl-7-(naphthalen-2-yloxy)[1,2,4]triazolo[1,5-a]pyrimidine
-
-
5-methyl-7-(naphthalen-2-ylsulfanyl)[1,2,4]triazolo[1,5-a]pyrimidine
-
-
5-methyl-N-(2,3,4-trifluorophenyl)[1,2,4]triazolo[1,5-a]pyrimidin-7-amine
-
-
5-methyl-N-(2,4,5-trifluorophenyl)[1,2,4]triazolo[1,5-a]pyrimidin-7-amine
-
-
5-methyl-N-(3-methylphenyl)[1,2,4]triazolo[1,5-a]pyrimidin-7-amine
-
-
5-methyl-N-(4-methylphenyl)[1,2,4]triazolo[1,5-a]pyrimidin-7-amine
-
-
5-methyl-N-(4-nitrophenyl)[1,2,4]triazolo[1,5-a]pyrimidin-7-amine
-
-
5-methyl-N-(naphthalen-2-yl)[1,2,4]triazolo[1,5-a]pyrimidin-7-amine
-
i.e. DSM1
5-methyl-N-(naphthalen-2-yl)[1,2,4]triazolo[1,5-a]pyrimidin-7-amine
-
-
5-methyl-N-[3-(trifluoromethyl)phenyl][1,2,4]triazolo[1,5-a]pyrimidin-7-amine
-
-
5-methyl-N-[4-(trifluoromethoxy)phenyl][1,2,4]triazolo[1,5-a]pyrimidin-7-amine
-
-
5-methyl-N-[4-(trifluoromethyl)phenyl][1,2,4]triazolo[1,5-a]pyrimidin-7-amine
-
i.e. DSM74
5-methyl-N-[4-(trifluoromethyl)phenyl][1,2,4]triazolo[1,5-a]pyrimidin-7-amine
-
-
5-methyl-N-[4-(trifluoromethyl)phenyl][1,2,4]triazolo[1,5-a]pyrimidin-7-amine
-
-
5-methyl-N-[4-methyl-3-(trifluoromethyl)phenyl][1,2,4]triazolo[1,5-a]pyrimidin-7-amine
-
-
5-Methylorotate
-
-
5-Methylorotate
-
-
6-chloro-2-(2'-fluorobiphenyl-4-yl)quinoline-4-carboxylic acid
-
-
-
6-methyl-N-phenyl-3aH-inden-4-amine
-
-
A77 1726
-
active metabolite of leflunomide
A77 1726
-
malononitrilamide, 50% inhibition at 18-773 nM
A77 1726
-
active metabolite of the anti-rheumatic drug leflunomide
A77 1726
-
inhibits cell growth in multiple myeloma cell lines at clinically achievable concentrations by induction of apoptosis. Inhibition of cell growth is partly due to inhibition of multiple myeloma cell proliferation. A77 1726 shows synergistic and additive activity together with genotoxic agents melphalan, treosulfan, and doxorubicin
A77-1726
-
50% inhibition at 0.00045 mM, wild-type, 0.00033 mM, DELTA2-21 mutant, 0.00031 mM, DELTA22-37 mutant, 0.00036 mM, DELTA2-37 mutant
atovaquone
-
-
atovaquone
-
competitive to quinone
atovaquone
-
50% inhibition at 0.000698 mM, wild-type enzyme, 0.000904 mM, DELTA1-29 mutant
Barbituric acid
-
competitive to dihydroorotate, dead-end inhibitor
Barbituric acid
-
-
benzoquinones
-
ubiquinone-0 and decylubiquinone
-
biphenyl-4-yl-(5-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-yl)-amine
-
-
-
brequinar
-
50% inhibition at 0.567 mM, wild-type, 0.528 mM, DELTA2-21 mutant, 0.615 mM, DELTA22-37 mutant, 0.662 mM, DELTA2-37 mutant
brequinar
-
50% inhibition at 0.000367 mM, wild-type enzyme, 0.000127 mM, DELTA1-29 mutant
brequinar
-
sensitive to brequinar at a 0.01 mM concentration
brequinar sodium
-
-
brequinar sodium
-
tight binding, most potent inhibitor, mutant H26A is insensitive, wild-type and other mutants are inhibited by 50% at concentrations between 6 and 10 nM
brequinar sodium
-
potent, noncompetitive inhibitor
brequinar sodium
-
more active than A77 1726 and HR325
brequinar sodium
-
50% inhibition at 6-127 nM
brequinar sodium
-
complete activity termination in all tissues at 0.01 mM
brequinar sodium
complete activity termination in all tissues at 0.01 mM
brequinar sodium
-
complete activity termination in all tissues at 0.01 mM
brequinar sodium
-
; inbibits by interference with the transfer of electrons from flavin to quinone
brequinar sodium
-
-
brequinar sodium
-
competitive versus ubiquinone, uncompetitive versus dihydroorotate, study of kinetics
brequinar sodium
1 mM reduces the activity by more than 50% of the full-length enzyme
chloronaphthoquinone
-
-
cis-5-methyldihydroorotate
-
-
deoxycholate
-
-
dichloroallyl lawsone
-
50% inhibition at 0.00051 mM, wild-type, 0.00031 mM, DELTA2-21 mutant, 0.00020 mM, DELTA22-37 mutant, 0.00021 mM, DELTA2-37 mutant
dichloroallyl-lawsone
-
competitive to quinone
diethyl [(1H-benzimidazol-5-ylamino)methylidene]propanedioate
-
-
diethyl [(1H-indazol-5-ylamino)methylidene]propanedioate
-
-
diethyl [(5a,9a-dihydrodibenzo[b,d]thiophen-2-ylamino)methylidene]propanedioate
-
-
diethyl [(biphenyl-3-ylamino)methylidene]propanedioate
-
-
diethyl [(biphenyl-4-ylamino)methylidene]propanedioate
-
-
diethyl [(dibenzo[b,d]thiophen-2-ylamino)methylidene]propanedioate
-
-
diethyl {[(2-methylphenyl)amino]methylidene}propanedioate
-
-
diethyl {[(4-methylphenyl)amino]methylidene}propanedioate
-
-
diethyldicarbonate
-
histidine-selective covalent modifier
diethyldicarbonate
-
histidine-selective covalent modifier; histidine-selective modifying agent, dose-dependent
Dodecyl sulfate
-
-
ethyl (2Z)-3-(biphenyl-3-ylamino)-2-cyanoprop-2-enoate
-
-
ethyl (2Z)-3-(biphenyl-4-ylamino)-2-cyanoprop-2-enoate
-
-
ethyl 4-(4-ethoxybenzyl)-3,5-dimethyl-1H-pyrrole-2-carboxylate
-
-
ethyl 4-(4-ethoxybenzyl)-3,5-dimethyl-1H-pyrrole-2-carboxylate
-
-
ethyl 4-(4-ethoxybenzyl)-3,5-dimethyl-1H-pyrrole-2-carboxylate
-
-
fatty acids
-
noncompetitive with respect to ubiquinone
fatty acids
-
-
H2O2
-
byproduct, tends to inactivate enzyme
HR325
-
structural analogue of A77 1726
-
MNA 279
-
malononitrilamide, 50% inhibition at 22-715 nM
N-(2,3-difluorophenyl)-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-7-amine
-
-
N-(2,4-dichlorophenyl)-2-naphthamide
-
50% inhibition at 0.00005 mM, wild type, 0.00008 mM, mutant R265A, above 0.05, mutant H185A
N-(2,4-dichlorophenyl)naphthalene-2-carboxamide
-
-
N-(2-chlorophenyl)-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-7-amine
-
-
N-(2-fluoro-4-methylphenyl)-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-7-amine
-
-
N-(2-fluorophenyl)-2-naphthamide
-
50% inhibition at 0.00047 mM, wild type, 0.00030 mM, mutant R265A, 0.21, mutant H185A
N-(2-fluorophenyl)-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-7-amine
-
-
N-(3,4-dichlorophenyl)-2-methyl-3-nitrobenzamide
-
50% inhibition at 0.00008 mM, wild type, 0.0028 mM, mutant R265A, 0.06, mutant H185A
N-(3,4-difluorophenyl)-2-methyl-3-nitrobenzamide
-
50% inhibition at 0.00026 mM, wild type, 0.00082 mM, mutant R265A, 0.25, mutant H185A
N-(3,4-difluorophenyl)-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-7-amine
-
-
N-(3,4-dimethylphenyl)-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-7-amine
-
-
N-(3,5-dichloro-phenyl)-2-methyl-3-nitro-benzamide
-
-
N-(3,5-dichlorophenyl)-2-methyl-3-nitrobenzamide
-
50% inhibition at 0.00002 mM, wild type, 0.0004 mM, mutant R265A, 0.13, mutant H185A
N-(3,5-dichlorophenyl)-2-methyl-3-nitrobenzamide
-
-
N-(3,5-difluorophenyl)-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-7-amine
-
-
N-(3-bromophenyl)-2-methyl-3-nitrobenzamide
-
50% inhibition at 0.00006 mM, wild type, 0.0012 mM, mutant R265A, 0.140, mutant H185A
N-(3-chloro-2'-methoxybiphenyl-4-yl)-2-cyano-3-hydroxybut-2-enamide
-
-
-
N-(3-chloro-4-fluorophenyl)-2-methyl-3-nitrobenzamide
-
50% inhibition at 0.0001 mM, wild type, 0.0005 mM, mutant R265A, 0.13, mutant H185A
N-(3-chlorophenyl)-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-7-amine
-
-
N-(3-chlorophenyl)-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-7-amine
-
-
N-(3-fluoro-4-methylphenyl)-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-7-amine
-
-
N-(3-fluorophenyl)-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-7-amine
-
-
N-(3-fluorophenyl)-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-7-amine
-
-
N-(4-benzylphenyl)-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-7-amine
-
-
N-(4-bromo-2-methylphenyl)-2-naphthamide
-
50% inhibition at 0.00005 mM, wild type, 0.00005 mM, mutant R265A, 0.57, mutant H185A
N-(4-bromophenyl)-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-7-amine
-
-
N-(4-bromophenyl)-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-7-amine
-
-
N-(4-chlorophenyl)-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-7-amine
-
-
N-(4-fluoro-3-methylphenyl)-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-7-amine
-
-
N-(4-fluorophenyl)-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-7-amine
-
-
N-(4-fluorophenyl)-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-7-amine
-
-
N-(4-methoxyphenyl)-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-7-amine
-
-
N-(anthracen-2-yl)-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-7-amine
-
-
N-(anthracen-2-yl)-N,5-dimethyl[1,2,4]triazolo[1,5-a]pyrimidin-7-amine
-
-
N-(biphenyl-4-yl)-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-7-amine
-
-
N-anthracen-2-yl-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-7-amine
-
i.e. DSM2
N-cyclopropyl-5-(2,3-dihydro-4H-1,4-benzothiazin-4-yl)thiophene-2-carboxamide
-
-
-
N-propyl-5-(1H-pyrazol-1-yl)thiophene-2-carboxamide
-
-
N-[3-fluoro-4-(trifluoromethyl)phenyl]-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-7-amine
-
-
N-[3-fluoro-4-(trifluoromethyl)phenyl]-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-7-amine
-
-
N-[4-(difluoromethoxy)phenyl]-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-7-amine
-
-
N-[4-bromo-3-(trifluoromethyl)phenyl]-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-7-amine
-
-
N-[4-chloro-3-(trifluoromethyl)phenyl]-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-7-amine
-
-
Orotate
-
competitive to dihydroorotate
Orotate
-
-
Orotate
-
also inhibitors: 5-substituted orotates; competitive to dihydroorotate; strong competitive inhibitor
Orotate
-
competitive to dihydroorotate
Orotate
-
-
Orotate
-
-
redoxal
-
50% inhibition at 45-88 nM
redoxal
-
50% inhibition at 0.029 mM, wild-type, 0.057 mM, DELTA2-21 mutant, 0.040 mM, DELTA22-37 mutant, 0.056 mM, DELTA2-37 mutant
redoxal
-
50% inhibition at 0.000013 mM, N-terminally truncated protein
redoxal
50% inhibition at 0.071 mM, N-terminally truncated protein
redoxal
0.5 mM exhibit an inhibitory effect of more than 50% on full-length DHODH and N-terminally truncated DHODH compared with the noninhibited reaction
rhodamine 123
-
mitochondrial inhibitor
teriflunomide
-
a redox-silent coenzyme Q antagonist of DHODH
Thenoyltrifluoroacetone
-
-
Thenoyltrifluoroacetone
-
-
toltrazuril
-
50% inhibition at 0.1 mM
toltrazuril
50% inhibition at 0.1 mM
toltrazuril
-
50% inhibition at 0.1 mM
[2-fluoro-2',5'-dimethyl-4'-[6-(3-methyl-2-butenyloxy)pyridin-3-yl]biphenyl-4-yl]-(3-methyl-2-butenyl)amine
-
i.e. S-2678, suppresses immunoglobulin production in human peripheral blood mononuclear cells in vitro, with little or no inhibition of cell proliferation
[2-fluoro-2',5'-dimethyl-4'-[6-(3-methyl-2-butenyloxy)pyridin-3-yl]biphenyl-4-yl]-(3-methyl-2-butenyl)amine
-
i.e. S-2678, suppresses immunoglobulin production in mouse B cells in vitro, with little or no inhibition of cell proliferation, probably through inhibitionof class switch recombination in the immunoglobulin heavy chain loci in B cells. In vivo antibody production induced by systemic immunization with ovalbumin is dramatically suppressed by oral administration of S-2678, without any toxicological signs. S-2678 does not affect T-cell activation in vitro, and cytokine production induced by intravenous anti-CD3 antibody in mice. S-2678 does not affect host defense in a mouse model of Candida infection, whereas leflunomide severely impaires it
MNA 715
-
malononitrilamide, 50% inhibition at 41-109 nM
additional information
-
not: bathophenathroline, sulfonate, ethylendiaminetetraacetate, cyanide, azide
-
additional information
-
kinetics of inhibition
-
additional information
-
competitive nature of small molecule inhibitors toward the putative ubiquinone binding site
-
additional information
-
DHODH-specific inhibitors with low nanomolar binding affinities bind in the N-terminal hydrophobic channel of dihydroorotate dehydrogenase, the presumed site of ubiquinone binding during oxidation of dihydroorotate to orotate
-
additional information
-
development and evaluation of triazolopyrimidine-based DHODH inhibitors, overview. Detailed quantitative structure-activity relationship study and molecular docking studies, the 2-methyltriazolopyrimidine ring interacts with some polar and some nonpolar amino acids whereas the substituted phenyl ring binds with a hydrophobic pocket of the enzyme formed by some nonpolar amino acid residues, overview
-
additional information
-
screening for potent inhibitors of PfDHODH and effect on the human enzyme, overview. The compiunds show strong selectivity for the malarial enzyme over that from the human host, inhibition mechanism, overview
-
additional information
-
screening for potent inhibitors of PfDHODH that show strong selectivity for the malarial enzyme over that from the human host. Lead optimization of a triazolopyrimidine-based series, inhibition mechanism, overview
-
additional information
-
drug screening and identification of a series of N-alkyl-5-(1H-benzimidazol-1-yl)thiophene-2-carboxamides with low nanomolar in vitro potency against DHODH, selective for the parasite enzymes over human DHODH, tolerability in the mouse, overview
-
additional information
-
drug screening and identifictaion of a series of N-alkyl-5-(1H-benzimidazol-1-yl)thiophene-2-carboxamides with low nanomolarin vitro potency against DHODH, selective for the parasite enzymes over human DHODH, tolerability in the mouse, overview
-
additional information
-
drug screening and identification of a series of N-alkyl-5-(1H-benzimidazol-1-yl)thiophene-2-carboxamides with low nanomolar in vitro potency against DHODH, selective for the parasite enzymes over human DHODH, tolerability in the mouse, overview
-
additional information
-
identification of a metabolically stable triazolopyrimidine-based dihydroorotate dehydrogenase inhibitor with antimalarial activity in mice, overview
-
additional information
-
not inhibitory: brequinar, atovaquone, N-(3,5-difluoro-4-(trifluoromethyl)phenyl)-5-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-amine
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
oxygen
seems to promote very low DHODH activity
additional information
-
activity of the bc1 complex is essential for providing oxidized ubiqinone to DHODH for the formation of pyrimidines
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.06
(S)-dihydroorotate
-
pH 8.0, 30C
0.076
(S)-dihydroorotate
-
wild-type, pH 8.0, 22C
0.265
(S)-dihydroorotate
-
mutant N302S, pH 8.0, 22C
0.028
1,4-Naphthoquinone
-
pH 8.0, 30C
0.099
2,3-dimethoxy-5-methyl-1,4-benzoquinone
-
pH 8.0, 30C
0.132
2,5-dimethyl-p-benzoquinone
-
pH 8.0, 30C
0.0146
2,6-dichlorophenolindophenol
-
S175C mutant
0.0058
2,6-dihydrophenolindophenol
-
-
7.8
coenzyme Q1
-
mutant I272A, pH 8.0, 25C
11
coenzyme Q1
-
wild-type, pH 8.0, 25C
15
coenzyme Q1
-
mutant F188A, pH 8.0, 25C
16
coenzyme Q1
-
mutant F227A, pH 8.0, 25C; mutant Y528A, pH 8.0, 25C
17
coenzyme Q1
-
mutant L531A, pH 8.0, 25C
20
coenzyme Q1
-
mutant Y528F, pH 8.0, 25C
22
coenzyme Q1
-
mutant H185A, pH 8.0, 25C
38
coenzyme Q1
-
mutant R265A, pH 8.0, 25C
48
coenzyme Q1
-
mutant Y528W, pH 8.0, 25C
0.0011
coenzyme Q6
-
-
0.014
coenzyme Q6
-
-
0.0142
coenzyme Q6
-
-
0.022
coenzyme Q6
-
-
0.0013
coenzyme Q7
-
cosubstrate benzyl-S-dihydroorotate
8.8
coenzyme QD
-
mutant Y528A, pH 8.0, 25C
12
coenzyme QD
-
mutant I272A, pH 8.0, 25C
13
coenzyme QD
-
wild-type, pH 8.0, 25C
16
coenzyme QD
-
mutant L531A, pH 8.0, 25C
20
coenzyme QD
-
mutant F188A, pH 8.0, 25C; mutant F227A, pH 8.0, 25C
26
coenzyme QD
-
mutant R265A, pH 8.0, 25C
34
coenzyme QD
-
mutant H185A, pH 8.0, 25C
45
coenzyme QD
-
mutant Y528W, pH 8.0, 25C
53
coenzyme QD
-
mutant Y528F, pH 8.0, 25C
0.0095
decyclubiquinone
-
recombinant enzyme
0.0065
decylubiquinone
-
expressed in SF21 insect cells
0.0095
decylubiquinone
-
expressed in Escherichia coli
0.011
decylubiquinone
-
wild-type recombinant enzyme
0.0113
decylubiquinone
-
DELTA22-37 mutant enzyme
0.0115
decylubiquinone
-
DELTA2-21 mutant enzyme
0.0118
decylubiquinone
-
DELTA2-37 mutant enzyme
0.013
decylubiquinone
-
mutant enzyme R265A; wild-type enzyme
0.0137
decylubiquinone
-
expressed in Escherichia coli
0.014
decylubiquinone
-
cosubstrate dihydroorotate
0.015
decylubiquinone
-
mutant N302S, pH 8.0, 22C
0.016
decylubiquinone
-
pH 8.0, 22C, wild-type
0.017
decylubiquinone
-
mutant enzyme F188A
0.019
decylubiquinone
-
mutant enzyme H185A
0.029
decylubiquinone
-
pH 8.0, 30C
0.032
decylubiquinone
pH 8.0, 25C, cosubstrate L-dihydroorotate, N-terminally truncated protein
0.032
decylubiquinone
-
pH 8.0, 22C, mutant R265A
0.037
decylubiquinone
-
wild-type, pH 8.0, 22C
0.066
decylubiquinone
-
pH 8.0, 22C, mutant H185A
0.112
decylubiquinone
pH 8.0, 30C, wild-type
0.341
decylubiquinone
pH 8.0, 30C, DELTA1-75 mutant
0.004
dihydroorotate
-
cosubstrate ubiquinone-50
0.005
dihydroorotate
-
0.009
dihydroorotate
-
-
0.009
dihydroorotate
-
cosubstrate decylubiquinone
0.01
dihydroorotate
-
-
0.013
dihydroorotate
-
mutant R265K; wild-type
0.014
dihydroorotate
-
-
0.015
dihydroorotate
-
recombinant enzyme
0.0164
dihydroorotate
-
DELTA2-21 mutant enzyme
0.0166
dihydroorotate
-
DELTA22-37 mutant enzyme
0.0167
dihydroorotate
-
DELTA2-37 mutant enzyme
0.017
dihydroorotate
-
wild-type recombinant enzyme
0.017
dihydroorotate
-
mutant F188A
0.019
dihydroorotate
-
mutant H185A
0.04
dihydroorotate
pH 8.0, 30C, wild-type
0.04
dihydroorotate
N-terminally truncated DHODH, fixed concentration of dihydroorotate and varied concentrations of 2,6-dichloroindophenol from 0-0.2 mM
0.042
dihydroorotate
full-length DHODH, fixed concentration of dihydroorotate of 1.0 mM and varied concentrations of decylubiquinone from 0-0.2 mM
0.065
dihydroorotate
N-terminally truncated DHODH, fixed concentration of dihydroorotate of 1.0 mM and varied concentrations of decylubiquinone from 0-0.2 mM
0.108
dihydroorotate
full-length DHODH, concentration of dihydroorotate varied from 0-1.0 mM at fixed concentrations of 0.1 mM decylubiquinone and 0.06 mM 2,6-dichloroindophenol
0.111
dihydroorotate
N-terminally truncated DHODH, concentration of dihydroorotate varied from 0-1.0 mM at fixed concentrations of 0.1 mM decylubiquinone and 0.06 mM 2,6-dichloroindophenol
0.121
dihydroorotate
pH 8.0, 30C, DELTA1-75 mutant
0.122
dihydroorotate
full-length DHODH, fixed concentration of dihydroorotate of 1.0 mM and varied concentrations of 2,6-dichloroindophenol from 0-0.2 mM
0.015
L-dihydroorotate
pH 8.0, 25C, cosubstrate Q6, N-terminally truncated protein
0.016
L-dihydroorotate
pH 8.0, 25C, cosubstrate QD, N-terminally truncated protein
0.021
L-dihydroorotate
pH 8.0, 25C, cosubstrate Q4, N-terminally truncated protein
0.031
L-dihydroorotate
-
wild-type enzyme
0.033
L-dihydroorotate
-
mutant enzyme H185A; mutant enzyme R265K
0.035
L-dihydroorotate
-
mutant enzyme F188A
0.056
L-dihydroorotate
pH 8.0, 25C, cosubstrate vitamin K3, N-terminally truncated protein
0.091
L-dihydroorotate
-
pH 8.0, 22C, wild-type
0.105
L-dihydroorotate
-
pH 8.0, 22C, mutant R265A
0.114
L-dihydroorotate
pH 8.0, 25C, cosubstrate Q0, N-terminally truncated protein
0.123
L-dihydroorotate
-
pH 8.0, 22C, mutant H185A
0.184
menadione
-
-
0.0154
methyl dihydroorotate
-
-
0.1542
methyl dihydroorotate
-
-
0.0062
S-dihydroorotate
-
expressed in Escherichia coli
0.0092
S-dihydroorotate
-
-
0.01
S-dihydroorotate
-
-
0.011
S-dihydroorotate
-
-
0.0135
S-dihydroorotate
-
expressed in SF21 insect cells
0.0144
S-dihydroorotate
-
-
0.0146
S-dihydroorotate
-
expressed in Escherichia coli
0.0155
S-dihydroorotate
-
-
0.026
S-dihydroorotate
-
-
0.0288
S-dihydroorotate
-
ubiquinone0 and 2,6-dichlorophenolindophenol mix
0.03
S-dihydroorotate
-
2,6-dichlorophenolindophenol sole electron acceptor
0.0929
S-dihydroorotate
-
S175C mutant
0.115
S-dihydroorotate
-
-
0.007
ubiquinone
-
-
0.014
ubiquinone
-
-
0.019
ubiquinone
-
0.062
ubiquinone
-
-
0.04
ubiquinone-0
-
-
0.075
ubiquinone-0
-
-
0.051
ubiquinone-30
-
pH 8.0, 30C
0.035
ubiquinone-4
pH 8.0, 25C, cosubstrate L-dihydroorotate, N-terminally truncated protein
0.01
ubiquinone-50
-
cosubstrate dihydroorotate
0.027
ubiquinone-50
-
pH 8.0, 30C
0.0225
ubiquinone-6
-
-
0.028
ubiquinone-6
-
-
0.062
ubiquinone-6
pH 8.0, 25C, cosubstrate L-dihydroorotate, N-terminally truncated protein
0.0019
methyl-S-dihydroorotate
-
-
-
additional information
additional information
-
relative Km-values for wild-type and mutants listed for (S)-dihydroorotate and ubiquinone-6
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
38
(S)-dihydroorotate
Toxoplasma gondii
-
mutant N302S, pH 8.0, 22C
82
(S)-dihydroorotate
Toxoplasma gondii
-
pH 8.0, 30C
86
(S)-dihydroorotate
Toxoplasma gondii
-
wild-type, pH 8.0, 22C
29
1,4-Naphthoquinone
Toxoplasma gondii
-
pH 8.0, 30C
32
2,3-dimethoxy-5-methyl-1,4-benzoquinone
Toxoplasma gondii
-
pH 8.0, 30C
44
2,5-dimethyl-p-benzoquinone
Toxoplasma gondii
-
pH 8.0, 30C
0.19
coenzyme Q1
Plasmodium falciparum
-
mutant Y528A, pH 8.0, 25C
1.5
coenzyme Q1
Plasmodium falciparum
-
mutant I272A, pH 8.0, 25C
1.9
coenzyme Q1
Plasmodium falciparum
-
mutant Y528F, pH 8.0, 25C
2.6
coenzyme Q1
Plasmodium falciparum
-
mutant F188A, pH 8.0, 25C; mutant F227A, pH 8.0, 25C
3.1
coenzyme Q1
Plasmodium falciparum
-
mutant R265A, pH 8.0, 25C
5.1
coenzyme Q1
Plasmodium falciparum
-
mutant L531A, pH 8.0, 25C; mutant Y528W, pH 8.0, 25C
7.3
coenzyme Q1
Plasmodium falciparum
-
mutant H185A, pH 8.0, 25C
7.8
coenzyme Q1
Plasmodium falciparum
-
wild-type, pH 8.0, 25C
44.2
coenzyme Q6
Bos taurus
-
-
0.12
coenzyme QD
Plasmodium falciparum
-
mutant Y528A, pH 8.0, 25C
1.2
coenzyme QD
Plasmodium falciparum
-
mutant Y528F, pH 8.0, 25C
1.8
coenzyme QD
Plasmodium falciparum
-
mutant I272A, pH 8.0, 25C
3.5
coenzyme QD
Plasmodium falciparum
-
mutant F227A, pH 8.0, 25C
4.3
coenzyme QD
Plasmodium falciparum
-
mutant F188A, pH 8.0, 25C
5
coenzyme QD
Plasmodium falciparum
-
mutant R265A, pH 8.0, 25C
6.8
coenzyme QD
Plasmodium falciparum
-
mutant Y528W, pH 8.0, 25C
7.9
coenzyme QD
Plasmodium falciparum
-
mutant H185A, pH 8.0, 25C
8.6
coenzyme QD
Plasmodium falciparum
-
mutant L531A, pH 8.0, 25C
12
coenzyme QD
Plasmodium falciparum
-
wild-type, pH 8.0, 25C
1.8
decylubiquinone
Plasmodium falciparum
Q08210
pH 8.0, 25C, cosubstrate L-dihydroorotate, N-terminally truncated protein
89
decylubiquinone
Toxoplasma gondii
-
pH 8.0, 30C
1.4
dihydroorotate
Plasmodium falciparum
-
mutant H185A
2.1
dihydroorotate
Candida albicans
Q874I4
full-length DHODH
2.2
dihydroorotate
Candida albicans
Q874I4
N-terminally truncated DHODH
8.2
dihydroorotate
Arabidopsis thaliana
P32746
pH 8.0, 30C, wild-type
12.3
dihydroorotate
Plasmodium falciparum
-
mutant F188A
15.8
dihydroorotate
Plasmodium falciparum
-
wild-type
16.1
dihydroorotate
Plasmodium falciparum
-
mutant R265K
50.4
dihydroorotate
Bos taurus
-
-
72.9
dihydroorotate
Arabidopsis thaliana
P32746
pH 8.0, 30C, DELTA1-75 mutant
1.4
L-dihydroorotate
Plasmodium falciparum
-
mutant enzyme H185A
1.7
L-dihydroorotate
Plasmodium falciparum
-
pH 8.0, 22C, mutant H185A
1.8
L-dihydroorotate
Plasmodium falciparum
Q08210
pH 8.0, 25C, cosubstrate Q0, N-terminally truncated protein
2
L-dihydroorotate
Plasmodium falciparum
Q08210
pH 8.0, 25C, cosubstrate Q4, N-terminally truncated protein; pH 8.0, 25C, cosubstrate Q6, N-terminally truncated protein; pH 8.0, 25C, cosubstrate QD, N-terminally truncated protein; pH 8.0, 25C, cosubstrate vitamin K3, N-terminally truncated protein
4.6
L-dihydroorotate
Plasmodium falciparum
-
pH 8.0, 22C, mutant R265A
4.8
L-dihydroorotate
Drosophila melanogaster
-
DELTA22-37 mutant enzyme
5.1
L-dihydroorotate
Drosophila melanogaster
-
DELTA2-21 mutant enzyme
7.5
L-dihydroorotate
Drosophila melanogaster
-
wild-type recombinant enzyme
7.8
L-dihydroorotate
Plasmodium falciparum
-
pH 8.0, 22C, wild-type
10.7
L-dihydroorotate
Drosophila melanogaster
-
DELTA2-37 mutant enzyme
12.3
L-dihydroorotate
Plasmodium falciparum
-
mutant enzyme F188A
15.8
L-dihydroorotate
Plasmodium falciparum
-
wild-type enzyme
16.1
L-dihydroorotate
Plasmodium falciparum
-
mutant enzyme R265K
18.3
menadione
Bos taurus
-
-
0.083
O2
Plasmodium falciparum
-
mutant I272A, pH 8.0, 25C
0.1
O2
Plasmodium falciparum
-
mutant Y528A, pH 8.0, 25C
0.18
O2
Plasmodium falciparum
-
mutant Y528W, pH 8.0, 25C
0.25
O2
Plasmodium falciparum
-
mutant L531A, pH 8.0, 25C
0.42
O2
Plasmodium falciparum
-
wild-type, pH 8.0, 25C
0.43
O2
Plasmodium falciparum
-
mutant F227A, pH 8.0, 25C
0.44
O2
Plasmodium falciparum
-
mutant R265A, pH 8.0, 25C
0.53
O2
Plasmodium falciparum
-
mutant F188A, pH 8.0, 25C
0.57
O2
Plasmodium falciparum
-
mutant H185A, pH 8.0, 25C
0.63
O2
Plasmodium falciparum
-
mutant Y528F, pH 8.0, 25C
0.25
S-dihydroorotate
Plasmodium falciparum
-
-
19.7
S-dihydroorotate
Escherichia coli
-
pH 8.5, 4C, with menadione
71
S-dihydroorotate
Mus musculus
-
-
75
S-dihydroorotate
Homo sapiens
-
-
95
S-dihydroorotate
Rattus norvegicus
-
-
21
ubiquinone-30
Toxoplasma gondii
-
pH 8.0, 30C
1.8
ubiquinone-4
Plasmodium falciparum
Q08210
pH 8.0, 25C, cosubstrate L-dihydroorotate, N-terminally truncated protein
61
ubiquinone-50
Toxoplasma gondii
-
pH 8.0, 30C
2
ubiquinone-6
Plasmodium falciparum
Q08210
pH 8.0, 25C, cosubstrate L-dihydroorotate, N-terminally truncated protein
0.36
ubiquinone6
Plasmodium falciparum
-
-
45.4
methyl-dihydroorotate
Bos taurus
-
-
additional information
additional information
Homo sapiens
-
relative turnover numbers for wild-type and mutants listed for (S)-dihydroorotate and ubiquinone6
-
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
140
(S)-dihydroorotate
Toxoplasma gondii
-
mutant N302S, pH 8.0, 22C
1637
1100
(S)-dihydroorotate
Toxoplasma gondii
-
wild-type, pH 8.0, 22C
1637
2300
decylubiquinone
Toxoplasma gondii
-
wild-type, pH 8.0, 22C
963
2500
decylubiquinone
Toxoplasma gondii
-
mutant N302S, pH 8.0, 22C
963
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.00005
2-cyano-3-(9-ethyl-9H-carbazol-3-ylamino)acrylic acid ethyl ester
-
-
0.0604
2-cyano-3-(9-ethyl-9H-carbazol-3-ylamino)acrylic acid ethyl ester
-
-
0.4
2-cyano-3-cyclopropyl-3-hydroxy-N-[4'-(nitro)phenyl]-propenamide
pH 8.0, 25C, varied substrate QD, N-terminally truncated protein
0.0002 - 0.0009
2-hydroxyethylidene-cyanoacetic acid 4-trifluoromethyl anilide
-
competitive to dihydroorotate
0.0002 - 0.0009
2-hydroxyethylidene-cyanoacetic acid 4-trifluoromethyl anilide
-
competitive to ubiquinone, non-competitive to dihydroorotate, parent compound leflunomide has no inhibitory effect at concentrations up to 0.001 mM
0.001
2-hydroxyethylidene-cyanoacetic acid 4-trifluoromethyl anilide
-
non-competitive to decyclubiquinone
0.16
3-hydroxy-2-(3,3-dichloroallyl)-1,4-naphthoquinone
pH 8.0, 25C, varied substrate L-dihydroorotate, N-terminally truncated protein
0.25
3-hydroxy-2-(3,3-dichloroallyl)-1,4-naphthoquinone
pH 8.0, 25C, varied substrate QD, N-terminally truncated protein
0.0244
5-aminoorotate
-
-
0.1408
5-bromoorotate
-
-
0.0151
5-Fluoroorotate
-
-
0.2246
5-iodoorotate
-
-
0.1185
5-Methylorotate
-
-
0.000698
atovaquone
-
-
0.015
atovaquone
-
-
0.092
Barbiturate
-
-
0.003
Barbituric acid
-
-
0.0000232
brequinar sodium
-
full-length native enzyme
0.0000265
brequinar sodium
-
recombinant enzyme
0.00001
dichloro-allyllawsone
-
-
0.000067
dichloro-allyllawsone
-
-
0.000061
Lapachol
-
-
0.000618
Lapachol
-
-
0.049
Lawsone
-
-
0.5
Lawsone
-
-
0.0134
Orotate
-
-
0.018
Orotate
-
-
0.0182
Orotate
-
-
0.0388
Orotate
-
-
0.005
Orotic acid
-
competitive to dihydroorotate
0.059
redoxal
pH 8.0, 25C, varied substrate L-dihydroorotate, N-terminally truncated protein
0.086
redoxal
pH 8.0, 25C, varied substrate QD, N-terminally truncated protein
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.000117
(2Z)-2-cyano-3-cyclopropyl-3-hydroxy-N-[4-(trifluoromethyl)phenyl]prop-2-enamide
Homo sapiens
-
-
-
0.0925
(2Z)-2-cyano-3-cyclopropyl-3-hydroxy-N-[4-(trifluoromethyl)phenyl]prop-2-enamide
Plasmodium falciparum
-
-
-
0.00018
(2Z)-2-cyano-N-(2',3-dichlorobiphenyl-4-yl)-3-hydroxybut-2-enamide
Homo sapiens
-
-
-
0.004
(2Z)-2-cyano-N-(2',3-dichlorobiphenyl-4-yl)-3-hydroxybut-2-enamide
Plasmodium falciparum
-
-
-
0.000022
(2Z)-2-cyano-N-(2,2'-dichlorobiphenyl-4-yl)-3-hydroxybut-2-enamide
Homo sapiens
-
-
-
0.165
(2Z)-2-cyano-N-(2,2'-dichlorobiphenyl-4-yl)-3-hydroxybut-2-enamide
Plasmodium falciparum
-
-
-
0.00019
(2Z)-2-cyano-N-(2,3'-dichlorobiphenyl-4-yl)-3-hydroxybut-2-enamide
Homo sapiens
-
-
-
0.2366
(2Z)-2-cyano-N-(2,3'-dichlorobiphenyl-4-yl)-3-hydroxybut-2-enamide
Plasmodium falciparum
-
-
-
0.00013
(2Z)-2-cyano-N-(3'-ethoxybiphenyl-4-yl)-3-hydroxybut-2-enamide
Homo sapiens
-
-
-
0.182
(2Z)-2-cyano-N-(3'-ethoxybiphenyl-4-yl)-3-hydroxybut-2-enamide
Plasmodium falciparum
-
-
-
0.00013
(2Z)-N-(2'-chlorobiphenyl-4-yl)-2-cyano-3-hydroxybut-2-enamide
Homo sapiens
-
-
-
0.0474
(2Z)-N-(2'-chlorobiphenyl-4-yl)-2-cyano-3-hydroxybut-2-enamide
Plasmodium falciparum
-
-
-
0.0002
(2Z)-N-(3-chloro-2'-methoxybiphenyl-4-yl)-2-cyano-3-hydroxybut-2-enamide
Homo sapiens
-
-
-
0.0086
(2Z)-N-(3-chloro-2'-methoxybiphenyl-4-yl)-2-cyano-3-hydroxybut-2-enamide
Plasmodium falciparum
-
-
-
0.00009
(2Z)-N-(biphenyl-4-yl)-2-cyano-3-hydroxybut-2-enamide
Homo sapiens
-
-
-
0.0257
(2Z)-N-(biphenyl-4-yl)-2-cyano-3-hydroxybut-2-enamide
Plasmodium falciparum
-
-
-
0.00017
(2Z)-N-[2'-chloro-3-(trifluoromethyl)biphenyl-4-yl]-2-cyano-3-hydroxybut-2-enamide
Homo sapiens
-
-
-
0.0062
(2Z)-N-[2'-chloro-3-(trifluoromethyl)biphenyl-4-yl]-2-cyano-3-hydroxybut-2-enamide
Plasmodium falciparum
-
-
-
0.00023
1-(2-methoxyphenyl)-3-naphthalen-1-ylurea
Plasmodium falciparum
-
pH not specified in the publication, temperature not specified in the publication
0.11
1-(2-methoxyphenyl)-3-naphthalen-1-ylurea
Homo sapiens
-
pH not specified in the publication, temperature not specified in the publication
0.554
1-hydroxy-2-dodecyl-4(1)quinolone
Toxoplasma gondii
-
wild-type, pH 8.0, 22C
-
1.635
1-hydroxy-2-dodecyl-4(1)quinolone
Toxoplasma gondii
-
mutant N302S, pH 8.0, 22C
-
0.00044
2-cyano-3-(9-ethyl-9H-carbazol-3-ylamino)acrylic acid ethyl ester
Plasmodium falciparum
-
IC50: 0.00044 mM
0.491
2-cyano-3-(9-ethyl-9H-carbazol-3-ylamino)acrylic acid ethyl ester
Homo sapiens
-
IC50: 0.491 mM
0.096
2-cyano-3-hydroxy-N-(2',3,3'-trichlorobiphenyl-4-yl)but-2-enamide
Toxoplasma gondii
-
pH 8.0, 30C
-
0.091
2-hydroxyethylidene-cyano acetic acid 4-trifluoromethyl anilide
Toxoplasma gondii
-
pH 8.0, 30C
0.000013
2-[(2,5-dichlorophenyl)sulfanyl]-5-ethyl[1,2,4]triazolo[1,5-a]pyrimidin-7-ol
Homo sapiens
-
or above, pH not specified in the publication, temperature not specified in the publication
0.1
2-[(2,5-dichlorophenyl)sulfanyl]-5-ethyl[1,2,4]triazolo[1,5-a]pyrimidin-7-ol
Plasmodium falciparum
-
or above, pH not specified in the publication, temperature not specified in the publication
0.000051
2-[(2,5-dichlorophenyl)sulfanyl]-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-7-ol
Homo sapiens
-
pH not specified in the publication, temperature not specified in the publication
0.011
2-[(2,5-dichlorophenyl)sulfanyl]-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-7-ol
Plasmodium falciparum
-
pH not specified in the publication, temperature not specified in the publication
0.0019
2-[(3,4-dichlorophenyl)sulfanyl]-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-7-ol
Plasmodium falciparum
-
pH not specified in the publication, temperature not specified in the publication
0.0065
2-[(3,4-dichlorophenyl)sulfanyl]-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-7-ol
Homo sapiens
-
pH not specified in the publication, temperature not specified in the publication
0.001
2-[(4-chlorophenyl)sulfanyl]-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-7-ol
Plasmodium falciparum
-
pH not specified in the publication, temperature not specified in the publication
0.039
2-[(4-chlorophenyl)sulfanyl]-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-7-ol
Homo sapiens
-
pH not specified in the publication, temperature not specified in the publication
0.00093
2-[(E)-2-(2-methylphenyl)ethenyl]quinolin-4-ol
Plasmodium falciparum
-
pH not specified in the publication, temperature not specified in the publication
0.03
2-[(E)-2-(2-methylphenyl)ethenyl]quinolin-4-ol
Homo sapiens
-
pH not specified in the publication, temperature not specified in the publication
0.00011
4-pentyl-1,3,4,10-tetrahydroacridin-9(2H)-one
Plasmodium berghei
-
pH 8.0
0.00034
4-pentyl-1,3,4,10-tetrahydroacridin-9(2H)-one
Plasmodium falciparum
-
pH 8.0
0.00034
4-pentyl-1,3,4,10-tetrahydroacridin-9(2H)-one
Plasmodium falciparum
-
pH not specified in the publication, temperature not specified in the publication
0.00051
4-pentyl-1,3,4,10-tetrahydroacridin-9(2H)-one
Plasmodium vivax
-
pH 8.0
0.03
4-pentyl-1,3,4,10-tetrahydroacridin-9(2H)-one
Homo sapiens
-
pH not specified in the publication, temperature not specified in the publication
0.00016
5,6-dimethyl-N-(naphthalen-2-yl)[1,2,4]triazolo[1,5-a]pyrimidin-7-amine
Plasmodium falciparum
-
pH not specified in the publication, temperature not specified in the publication
0.00047
5-(1H-benzimidazol-1-yl)-N-propylthiophene-2-carboxamide
Homo sapiens
-
pH not specified in the publication, temperature not specified in the publication
0.0007
5-(1H-benzimidazol-1-yl)-N-propylthiophene-2-carboxamide
Plasmodium falciparum
-
pH not specified in the publication, temperature not specified in the publication
0.00046
5-(1H-indol-1-yl)-N-propylthiophene-2-carboxamide
Plasmodium falciparum
-
pH not specified in the publication, temperature not specified in the publication
0.00071
5-(1H-indol-1-yl)-N-propylthiophene-2-carboxamide
Homo sapiens
-
pH not specified in the publication, temperature not specified in the publication
0.00017
5-(2-methyl-1H-benzimidazol-1-yl)-N-propylthiophene-2-carboxamide
Plasmodium falciparum
-
pH not specified in the publication, temperature not specified in the publication
0.00063
5-(2-methyl-1H-benzimidazol-1-yl)-N-propylthiophene-2-carboxamide
Homo sapiens
-
pH not specified in the publication, temperature not specified in the publication
0.000042
5-(2-methyl-1H-indol-1-yl)-N-propylthiophene-2-carboxamide
Plasmodium falciparum
-
pH 8.0
0.000042
5-(2-methyl-1H-indol-1-yl)-N-propylthiophene-2-carboxamide
Plasmodium falciparum
-
pH not specified in the publication, temperature not specified in the publication
0.00006
5-(2-methyl-1H-indol-1-yl)-N-propylthiophene-2-carboxamide
Plasmodium berghei
-
pH 8.0
0.00042
5-(2-methyl-1H-indol-1-yl)-N-propylthiophene-2-carboxamide
Plasmodium vivax
-
pH 8.0
0.03
5-(2-methyl-1H-indol-1-yl)-N-propylthiophene-2-carboxamide
Homo sapiens
-
pH not specified in the publication, temperature not specified in the publication
0.01
5-(4-methylpiperazin-1-yl)-N-propylthiophene-2-carboxamide
Homo sapiens
-
above, pH not specified in the publication, temperature not specified in the publication
0.03
5-(4-methylpiperazin-1-yl)-N-propylthiophene-2-carboxamide
Plasmodium falciparum
-
pH not specified in the publication, temperature not specified in the publication
0.01
5-(piperidin-1-yl)-N-propylthiophene-2-carboxamide
Homo sapiens
-
above, pH not specified in the publication, temperature not specified in the publication
0.03
5-(piperidin-1-yl)-N-propylthiophene-2-carboxamide
Plasmodium falciparum
-
pH not specified in the publication, temperature not specified in the publication
0.00019
5-ethyl-N-(naphthalen-2-yl)[1,2,4]triazolo[1,5-a]pyrimidin-7-amine
Plasmodium falciparum
-
pH not specified in the publication, temperature not specified in the publication
0.000081
5-methoxy-2-[(4-phenoxyphenyl)amino]benzoic acid
Homo sapiens
-
pH 8.0, 22C
0.0017
5-methyl-7-(naphthalen-2-yloxy)[1,2,4]triazolo[1,5-a]pyrimidine
Plasmodium falciparum
-
pH not specified in the publication, temperature not specified in the publication
0.1
5-methyl-7-(naphthalen-2-ylsulfanyl)[1,2,4]triazolo[1,5-a]pyrimidine
Plasmodium falciparum
-
above, pH not specified in the publication, temperature not specified in the publication
0.000047
5-methyl-N-(naphthalen-2-yl)[1,2,4]triazolo[1,5-a]pyrimidin-7-amine
Plasmodium falciparum
-
pH not specified in the publication, temperature not specified in the publication
0.0013
5-methyl-N-(naphthalen-2-yl)[1,2,4]triazolo[1,5-a]pyrimidin-7-amine
Plasmodium falciparum
-
pH 8.0, 20C, mutant F227A; pH 8.0, 20C, mutant H185A
0.0021
5-methyl-N-(naphthalen-2-yl)[1,2,4]triazolo[1,5-a]pyrimidin-7-amine
Plasmodium falciparum
-
pH 8.0, 20C, mutant F188A; pH 8.0, 20C, mutant R265A
0.2
5-methyl-N-(naphthalen-2-yl)[1,2,4]triazolo[1,5-a]pyrimidin-7-amine
Homo sapiens
-
pH not specified in the publication, temperature not specified in the publication
0.00028
5-methyl-N-[4-(trifluoromethyl)phenyl][1,2,4]triazolo[1,5-a]pyrimidin-7-amine
Plasmodium falciparum
-
pH not specified in the publication, temperature not specified in the publication
0.00029
5-methyl-N-[4-(trifluoromethyl)phenyl][1,2,4]triazolo[1,5-a]pyrimidin-7-amine
Homo sapiens
-
pH not specified in the publication, temperature not specified in the publication
0.0014
5-methyl-N-[4-(trifluoromethyl)phenyl][1,2,4]triazolo[1,5-a]pyrimidin-7-amine
Plasmodium falciparum
-
pH 8.0, 20C, mutant F188A
0.0063
5-methyl-N-[4-(trifluoromethyl)phenyl][1,2,4]triazolo[1,5-a]pyrimidin-7-amine
Plasmodium falciparum
-
pH 8.0, 20C, mutant F227A
0.023
5-methyl-N-[4-(trifluoromethyl)phenyl][1,2,4]triazolo[1,5-a]pyrimidin-7-amine
Plasmodium falciparum
-
pH 8.0, 20C, mutant R265A
0.025
5-methyl-N-[4-(trifluoromethyl)phenyl][1,2,4]triazolo[1,5-a]pyrimidin-7-amine
Plasmodium falciparum
-
pH 8.0, 20C, mutant H185A
0.000015
6-chloro-2-(2'-fluorobiphenyl-4-yl)quinoline-4-carboxylic acid
Homo sapiens
-
pH 8.0, 22C
-
0.00016
diethyl [(dibenzo[b,d]thiophen-2-ylamino)methylidene]propanedioate
Plasmodium falciparum
-
pH not specified in the publication, temperature not specified in the publication
0.03
diethyl [(dibenzo[b,d]thiophen-2-ylamino)methylidene]propanedioate
Homo sapiens
-
pH not specified in the publication, temperature not specified in the publication
0.00004
ethyl 4-(4-ethoxybenzyl)-3,5-dimethyl-1H-pyrrole-2-carboxylate
Plasmodium vivax
-
pH 8.0
0.00006
ethyl 4-(4-ethoxybenzyl)-3,5-dimethyl-1H-pyrrole-2-carboxylate
Plasmodium berghei
-
pH 8.0
0.000083
ethyl 4-(4-ethoxybenzyl)-3,5-dimethyl-1H-pyrrole-2-carboxylate
Plasmodium falciparum
-
pH 8.0
0.000083
ethyl 4-(4-ethoxybenzyl)-3,5-dimethyl-1H-pyrrole-2-carboxylate
Plasmodium falciparum
-
pH not specified in the publication, temperature not specified in the publication
0.03
ethyl 4-(4-ethoxybenzyl)-3,5-dimethyl-1H-pyrrole-2-carboxylate
Homo sapiens
-
pH not specified in the publication, temperature not specified in the publication
0.000014
Genz-667348
Plasmodium berghei
-
pH 8.0, temperature not specified in the publication
0.000022
Genz-667348
Plasmodium falciparum
-
pH 8.0, temperature not specified in the publication
0.000042
Genz-667348
Plasmodium vivax
-
pH 8.0, temperature not specified in the publication
0.000012
Genz-668857
Plasmodium berghei
-
pH 8.0, temperature not specified in the publication
0.000015
Genz-668857
Plasmodium vivax
-
pH 8.0, temperature not specified in the publication
0.000044
Genz-668857
Plasmodium falciparum
-
pH 8.0, temperature not specified in the publication
0.000015
Genz-669178
Plasmodium vivax
-
pH 8.0, temperature not specified in the publication
0.00004
Genz-669178
Plasmodium berghei
-
pH 8.0, temperature not specified in the publication
0.00005
Genz-669178
Plasmodium falciparum
-
pH 8.0, temperature not specified in the publication
0.00005
N-(2,4-dichlorophenyl)naphthalene-2-carboxamide
Plasmodium falciparum
-
pH not specified in the publication, temperature not specified in the publication
0.05
N-(2,4-dichlorophenyl)naphthalene-2-carboxamide
Homo sapiens
-
pH not specified in the publication, temperature not specified in the publication
0.1
N-(2-chlorophenyl)-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-7-amine
Plasmodium falciparum
-
above, pH not specified in the publication, temperature not specified in the publication
0.1
N-(2-fluorophenyl)-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-7-amine
Plasmodium falciparum
-
above, pH not specified in the publication, temperature not specified in the publication
0.049
N-(3,5-dichloro-phenyl)-2-methyl-3-nitro-benzamide
Plasmodium falciparum
-
wild-type, pH 8.0, 25C
0.087
N-(3,5-dichloro-phenyl)-2-methyl-3-nitro-benzamide
Plasmodium falciparum
-
mutant L531A, pH 8.0, 25C
0.1
N-(3,5-dichloro-phenyl)-2-methyl-3-nitro-benzamide
Plasmodium falciparum
-
mutant R265A, pH 8.0, 25C
1.9
N-(3,5-dichloro-phenyl)-2-methyl-3-nitro-benzamide
Plasmodium falciparum
-
mutant F188A, pH 8.0, 25C
2.9
N-(3,5-dichloro-phenyl)-2-methyl-3-nitro-benzamide
Plasmodium falciparum
-
mutant H185A, pH 8.0, 25C
12
N-(3,5-dichloro-phenyl)-2-methyl-3-nitro-benzamide
Plasmodium falciparum
-
mutant F227A, pH 8.0, 25C
0.000016
N-(3,5-dichlorophenyl)-2-methyl-3-nitrobenzamide
Plasmodium falciparum
-
pH not specified in the publication, temperature not specified in the publication
0.2
N-(3,5-dichlorophenyl)-2-methyl-3-nitrobenzamide
Homo sapiens
-
pH not specified in the publication, temperature not specified in the publication
0.06
N-(3-chloro-2'-methoxybiphenyl-4-yl)-2-cyano-3-hydroxybut-2-enamide
Toxoplasma gondii
-
pH 8.0, 30C
-
0.00068
N-(3-chlorophenyl)-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-7-amine
Homo sapiens
-
pH not specified in the publication, temperature not specified in the publication
0.0014
N-(3-chlorophenyl)-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-7-amine
Plasmodium falciparum
-
pH not specified in the publication, temperature not specified in the publication
0.0005
N-(3-fluorophenyl)-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-7-amine
Homo sapiens
-
pH not specified in the publication, temperature not specified in the publication
0.0092
N-(3-fluorophenyl)-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-7-amine
Plasmodium falciparum
-
pH not specified in the publication, temperature not specified in the publication
0.00078
N-(4-bromophenyl)-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-7-amine
Plasmodium falciparum
-
pH not specified in the publication, temperature not specified in the publication
0.019
N-(4-fluorophenyl)-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-7-amine
Plasmodium falciparum
-
pH not specified in the publication, temperature not specified in the publication
0.000056
N-(anthracen-2-yl)-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-7-amine
Plasmodium falciparum
-
pH not specified in the publication, temperature not specified in the publication
0.0007
N-(anthracen-2-yl)-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-7-amine
Homo sapiens
-
pH not specified in the publication, temperature not specified in the publication
0.003
N-(anthracen-2-yl)-N,5-dimethyl[1,2,4]triazolo[1,5-a]pyrimidin-7-amine
Plasmodium falciparum
-
pH not specified in the publication, temperature not specified in the publication
0.00021
N-anthracen-2-yl-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-7-amine
Plasmodium falciparum
-
pH 8.0, 20C, mutant F188A
0.0013
N-anthracen-2-yl-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-7-amine
Plasmodium falciparum
-
pH 8.0, 20C, mutant H185A
0.0024
N-anthracen-2-yl-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-7-amine
Plasmodium falciparum
-
pH 8.0, 20C, mutant R265A
0.0044
N-anthracen-2-yl-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-7-amine
Plasmodium falciparum
-
pH 8.0, 20C, mutant F227A
0.00025
N-cyclopropyl-5-(2,3-dihydro-4H-1,4-benzothiazin-4-yl)thiophene-2-carboxamide
Plasmodium falciparum
-
pH 8.0
-
0.00028
N-cyclopropyl-5-(2,3-dihydro-4H-1,4-benzothiazin-4-yl)thiophene-2-carboxamide
Plasmodium vivax
-
pH 8.0
-
0.00038
N-cyclopropyl-5-(2,3-dihydro-4H-1,4-benzothiazin-4-yl)thiophene-2-carboxamide
Plasmodium berghei
-
pH 8.0
-
0.01
N-propyl-5-(1H-pyrazol-1-yl)thiophene-2-carboxamide
Homo sapiens
-
above, pH not specified in the publication, temperature not specified in the publication
0.03
N-propyl-5-(1H-pyrazol-1-yl)thiophene-2-carboxamide
Plasmodium falciparum
-
pH not specified in the publication, temperature not specified in the publication
0.000077
N-[3-fluoro-4-(trifluoromethyl)phenyl]-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-7-amine
Plasmodium falciparum
-
pH not specified in the publication, temperature not specified in the publication
0.1
6-methyl-N-phenyl-3aH-inden-4-amine
Plasmodium falciparum
-
above, pH not specified in the publication, temperature not specified in the publication
additional information
A77 1726
Homo sapiens
-
IC50 value 440 ng per ml
additional information
A77 1726
Mus musculus
-
IC50 value 150 ng per ml
0.00021
N-[3-fluoro-4-(trifluoromethyl)phenyl]-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-7-amine
Homo sapiens
-
pH not specified in the publication, temperature not specified in the publication
additional information
[2-fluoro-2',5'-dimethyl-4'-[6-(3-methyl-2-butenyloxy)pyridin-3-yl]biphenyl-4-yl]-(3-methyl-2-butenyl)amine
Homo sapiens
-
IC50 value 23 ng per ml
additional information
[2-fluoro-2',5'-dimethyl-4'-[6-(3-methyl-2-butenyloxy)pyridin-3-yl]biphenyl-4-yl]-(3-methyl-2-butenyl)amine
Mus musculus
-
IC50 value 32 ng per ml
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.0002672
-
37C
0.0026
-
kidney
0.0026
-
liver
0.0054
-
kidney
0.0066
-
heart
0.0078
-
heart
0.015
-
EAT cells
1.1 - 23
-
with 0.5 mM fumarate
1.49
-
-
6
using decylubiquinone and 2,6-dichloroindophenol as acceptor
7.4 - 58
-
with 0.02 mM decylubiquinone
9.1 - 14.5
-
with 0.02 mM menadione
9.6
-
recombinant enzyme, electron acceptor decylubiquinone
20 - 24
-
with 0.02 mM ubiquinone0
22
-
with 0.02 mM 2,6-dichlorophenolindophenol
83
-
expressed in Escherichia coli
84
-
pH 8.0, 30C
99
-
with L-dihydroorotate and 2,6-dichloroindophenol as substrates, at 30C
103
-
-
130
-
expressed in SF21 insect cells
130 - 150
-
-
150
-
; expressed in Escherichia coli
119000
-
cosubstrate O2, pH 7.5
245000
-
cosubstrate 2,6-dichlorophenolindophenol, pH 7.5
548000
-
cosubstrate Q1, pH 7.5
additional information
highest activities in ileum and colon
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
6.8
-
particulate enzyme
7.1
-
dihydroorotate + 2,6-dichlorophenolindophenol
7.5
-
assay at
8
-
assay at
8
-
full-length native enzyme
8
-
solubilized enzyme
8
N-terminally truncated protein
8 - 8.1
-
; recombinant enzymes with His-tags
8.5
-
recombinant enzyme
additional information
8.0-8.5
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
6 - 10
-
no activity below pH 6.0 and above pH 10.0
6 - 11.3
-
the rate constant for flavin reduction increases with pH
6.5 - 8.5
-
-
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
23
-
assay at
37
-
assay at
60
-
no optimum found in the range 20C to 60C, activity increases up to 60C
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
; presence of enzymatically active DHODH in many regions of the central nervous system, albeit at different intensities. High levels of both DHODH activity and immunoreactivity are observed in the neocortex, hippocampus, spinal cord and choroid plexus. Lower levels are seen in the cerebellum, and only marginal expression in brain stem
Manually annotated by BRENDA team
-
very low enzyme level; very low level both of expression and activity
Manually annotated by BRENDA team
-
regiospecific distribution of DHODH, immunohistochemic analysis, overview
Manually annotated by BRENDA team
-
low enzyme level; low level both of expression and activity
Manually annotated by BRENDA team
-
high level both of expression and activity
Manually annotated by BRENDA team
-
premalignant
Manually annotated by BRENDA team
-
high enzyme level; high level both of expression and activity
Manually annotated by BRENDA team
-
high level both of expression and activity
Manually annotated by BRENDA team
-
DHODH protein is expressed in premalignant and malignant prostate epithelial cells
Manually annotated by BRENDA team
-
DHODH protein is expressed in premalignant and malignant skin cells
Manually annotated by BRENDA team
-
high level both of expression and activity
Manually annotated by BRENDA team
-
promyelomonocytic, histiocytic
Manually annotated by BRENDA team
additional information
-
distribution in various tissues
Manually annotated by BRENDA team
additional information
distribution in various tissues
Manually annotated by BRENDA team
additional information
-
no activity in colorectal carcinoma cells
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
electron spin resonance spectra show that the N-terminal binds to membranes and experiences a somewhat high flexibility that could be related to the role of this region as a molecular lid controlling the entrance of the enzyme's active site and thus allowing the enzyme to give access to quinones that are dispersed in the membrane and that are necessary for the catalysis
Manually annotated by BRENDA team
-
inner membrane; integral protein
Manually annotated by BRENDA team
-
inner membrane
Manually annotated by BRENDA team
-
a class 2 mitochondrial enzyme
Manually annotated by BRENDA team
PDB
SCOP
CATH
ORGANISM
UNIPROT
Escherichia coli (strain K12)
Streptococcus mutans serotype c (strain ATCC 700610 / UA159)
Trypanosoma brucei brucei (strain 927/4 GUTat10.1)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
35000
-
gel filtration
656747
39000
-
-
390921
42000
-
SDS-PAGE, glycerol gradient ultracentrifugation
391224
42000
-
gel filtration, truncated recombinant protein
391233
56000
-
gel filtration; gel filtration, SDS-PAGE
390929
67000
-
gel filtration
390918, 391227
72000
-
sedimentation analysis in sucrose density gradient in presence of detergent
390918
75000
-
sedimentation in sucrose density gradients
390918
80000
-
gel filtration
390930
120000
-
gel filtration
390922
130000
-
gel filtration
390923
210000
-
gel filtration after phospholipase treatment
391223
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
?
-
? * 40000; x * 40000, recombinant enzyme, SDS-PAGE, x * 50000, native full-length enzyme, SDS-PAGE
?
-
? * 43000; x * 43000, SDS-PAGE
?
-
x * 43000, SDS-PAGE
?
-
x * 45100, SDS-PAGE, recombinant from SF21 insect cells, x * 45000, SDS-PAGE, recombinant from Escherichia coli
?
x * 48500, deduced from gene sequendce
?
48000 for the full-length enzyme and 42000 for the truncated enzyme, SDS-PAGE
dimer
-
2 * 37000, residue S175 is critical for activity; 2 * 37000, SDS-PAGE, DNA-sequence, 2 * 36800, MALDI MS
dimer
-
2 * 36000, SDS-PAGE
homodimer
-
2 * 34000, SDS-PAGE, dynamic light scattering analysis
monomer
-
-
monomer
-
1 * 56000, SDS-PAGE; SDS-PAGE
monomer
-
1 * 42000, SDS-PAGE, glycerol gradient centrifugation
monomer
-
SDS-PAGE, truncated recombinant protein
monomer
-
folds into small N-terminal domain and an (alphabeta)8 barrel comprising the C-terminal domain, crystallization data
additional information
-
Plasmodium enzyme structure comparisons, molecular modeling, overview
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
lipoprotein
-
contains solvent-extractable fatty acids and phospholipids
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
; yellow crystals, space group P4(1)2(1)2 or P4(3)2(1)2
-
in complex with inhibitors (2Z)-N-(biphenyl-4-yl)-2-cyano-3-hydroxybut-2-enamide, (2Z)-N-(3-chloro-2'-methoxybiphenyl-4-yl)-2-cyano-3-hydroxybut-2-enamide, (2Z)-2-cyano-N-(2,2'-dichlorobiphenyl-4-yl)-3-hydroxybut-2-enamide, and (2Z)-2-cyano-N-(3'-ethoxybiphenyl-4-yl)-3-hydroxybut-2-enamide
-
in complex with inhibitors 2-[(2,5-dichlorophenyl)sulfanyl]-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-7-ol and 2-[(2,5-dichlorophenyl)sulfanyl]-5-ethyl[1,2,4]triazolo[1,5-a]pyrimidin-7-ol. bindung induces a structural change in the N-terminal helix. Comparison with binding to Plasmodium falciparum enzyme
-
in complex with inhibitors 6-chloro-2-(2'-fluorobiphenyl-4-yl)quinoline-4-carboxylic acid and and without any bound inhibitor, to 2.3 A, 2.1 A, and 3.0 A resolution, respectively. Inhibitor 5-methoxy-2-[(4-phenoxyphenyl)amino]benzoic acid 5-methoxy-2-[(4-phenoxyphenyl)amino]benzoic acid interacts with residue Y356. Loop region of residues L68-R72 may interfere with inhibitor/cofactor binding. Loop region N212-L224 may be important for the enzymatic reaction
-
in complex with low molecular weight compounds that inhibit the enzyme in the nanomolar range, by hanging-drop vapor diffusion method, to 2.15 A resolution
-
all compounds that were found to be inhibitors are predicted, using SPROUT, a software package for structure-based drug discovery and lead optimization, to bind in a manner similar to that observed for compound (2Z)-N-(biphenyl-4-yl)-2-cyano-3-hydroxybut-2-enamide, with the planar headgroup making direct hydrogen bonds to residues Arg265, His185, and Tyr528. The biphenyl tail of each inhibitor is predicted to bind in the large hydrophobic region of the binding cavity, in a fashion analogous to that found for these inhibitors in human DHODH. The substituted biaryl moiety present in these inhibitors is predicted to occupy the binding cavity more extensively compared to that of compound (2Z)-N-(biphenyl-4-yl)-2-cyano-3-hydroxybut-2-enamide
-
in complex with inhibitors 5-methyl-N-(naphthalen-2-yl)[1,2,4]triazolo[1,5-a]pyrimidin-7-amine, N-anthracen-2-yl-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-7-amine, and 5-methyl-N-[4-(trifluoromethyl)phenyl][1,2,4]triazolo[1,5-a]pyrimidin-7-amine to 2.0 A, 2.4 A, and 2.5 A resolution, respectively
-
purified recombinant His-tagged mutant DHODDELTA384-413 free or in complex with Genz-667348, hanging drop vapour diffusion method, 20C, mixing reservoir solution A containing 0.16 M ammonium sulfate, 0.1 M sodium acetate, pH 4.4, 14-15% PEG 4000, 25% glycerol, and 10 mM DTT, with an equal volume of 20 mg/ml protein pre-equilibrated with 0.6 mM Genz-667348, and 2 mM dihydroorotate, X-ray diffraction structure determination and analysis at 2.4 A resolution, molecular replacement
-
mutant DELTA1-29 in complex with brequinar and with atovaquone
-
pH STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
6
-
unstable below
391224
6 - 12.7
-
-
390919
6.5 - 10.5
-
stable
391224
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
4
-
t1/2: 2.5 months
391224
37
-
unstable with O2
390918
37
-
3 h
391224
50
-
Tm-value
390918
70
-
Tm-value
390918
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
dihydroorotate stabilizes during purification and dialysis and heat inactivation
-
dihydroorotate stabilizes
-
OXIDATION STABILITY
ORGANISM
UNIPROT
LITERATURE
reoxidation by O2 results in H2O2 which appears in the active site and is very harmful to a cysteine residue, H2O2 inactivates the enzyme
-
390918
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-80C, slight activity loss after freezing and storage
-
4C, pH 9.0, 50 mM Tris/HCl buffer, 0.1% Triton X-100, 3-4 weeks, t1/2: 2.5 months
-
-80C, slight activity loss after freezing and storage
-
-20C, 50% glycerol, 1 mM DTT, 0.01 mM FMN, no loss of activity during time of studies
-
-18C, stable
-
-20C, 10 mg/ml, 50 mM sodium phosphate, pH 7.0, 0.1 mM EDTA, 50% glycerol
-
-70C, flash frozen
-
-80C, slight activity loss after freezing and storage
-
great inactivation by repeated thawing and freezing
-
-80C, slight activity loss after freezing and storage
-
great inactivation by repeated thawing and freezing
-
-20C, several days
-
-80C, addition of S-dihydroorotate to stabilize the enzyme activity
-
4C, extremely labile, 90% decrease of activity over night
-
-80C, slight activity loss after freezing and storage
great inactivation by repeated thawing and freezing
-
4C, 12 days, 10 mM dihydroorotate
-
-80C, slight activity loss after freezing and storage
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
full-length DHODH and N-terminally truncated DHODH, by affinity chromatography
recombinant protein, His8-tag
-
streptomycin sulfate precipitation, anion-exchange, gel filtration
-
ion-exchange, ammonium sulfate precipitation, gel filtration
-
; ion-exchange, hydroxyapatite, gel filtration for U937, cation-exchange for spleen
-
ammonium sulfate precipitation, affinity chromatography, ion-exchange chromatography
-
by nickel agarose chromatography
-
Ni2+/nitrilotriacetate column
-
Ni2+/nitrilotriacetate column
-
; cation-, anion-exchange, gel filtration
-
by nickel agarose chromatography
-
recombinant His-tagged mutant DHODDELTA384-413 from Escherichia coli by affinity chromatography and gel filtration
-
Ni2+/nitrilotriacetate column
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
full-length DHODH and N-terminally truncated DHODH, which lacks the targeting sequence and the transmembrane domain recombinantly expressed in Escherichia coli BL21
; expression in Escherichia coli BL21(DE3) TAP330, a pyrD(-) minus derivative
-
overexpression of Escherichia coli dihyroorotate dehyrogenase in same strain, partially deleted for the chromosomal pyrD gene, clone selection followed by ampicillin and by complementation of the pyrimidine requirement
-
; expressed in Escherichia coli DH5alpha TAP330, lacking the endogenous gene for the bacterial dihydroorotate dehydrogenase, pyrimidine auxotroph
-
expressed in Escherichia coli DH5alpha TAP330, lacking the endogenous gene for the bacterial dihydroorotate dehydrogenase, pyrimidine auxotroph
-
expressed in Escherichia coli XL-1 Blue, histidine tagged
-
expressed in pyr4 mutants of Ustilago maydis
-
expression in Escherichia coli pyrD using a construct with His-tag fusion
-
expression of GFP-tagged enzyme in SW480 cells
-
expressed in Escherichia coli XL-1 Blue, histidine tagged
-
expression in Escherichia coli
-
expression in Escherichia coli pyrD using a construct with His-tag fusion
-
expression of the expression construct pET28b-TEVpfDHODDELTA384413 in Escherichia coli strain BL21
-
expressed in Escherichia coli XL-1 Blue, histidine tagged
-
expressed in Escherichia coli XL-1 Blue, histidine tagged; expression of complete catalytically active enzyme in SF21 insect cells of Spodoptera frugiperda with baculovirus vector system
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
suppression of enzyme expression by siRNA of DHODH
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
DELTA1-75
N-terminally truncated enzyme, drastic increase in kcat- and KM-value
L11S
two CUG codons in the DHODH ORF changed to UCG by site-directed PCR mutagenesis for gene expression in the bacterial system
L78S
two CUG codons in the DHODH ORF changed to UCG by site-directed PCR mutagenesis for gene expression in the bacterial system
DELTA2-21
-
instable in vivo
DELTA2-37
-
instable in vivo
DELTA22-37
-
instable in vivo
F115A
-
mutation slows the rate of flavin reduction by 3 orders of magnitude
F21C/R1C
mutant incorporates into 1-dipalmitoyl-2-oleoyl-sn-glycero-3-phosphocholine/Triton X-100 mixed vesicles and expected to be located right in the core of the more hydrophobic region of the model membrane. Mutated amino acids are either in a strongly immobilized regime or subjected to a fast motion
F5C/R1C
mutant incorporates into 1-dipalmitoyl-2-oleoyl-sn-glycero-3-phosphocholine/Triton X-100 mixed vesicles. Mutated residues experience a high degree of freedom that is compatible with their location in the beginning of the protein chain. Mutated amino acids are either in a strongly immobilized regime or subjected to a fast motion
H19C/R1C
mutant incorporates into 1-dipalmitoyl-2-oleoyl-sn-glycero-3-phosphocholine/Triton X-100 mixed vesicles and expected to be located right in the core of the more hydrophobic region of the model membrane. Mutated amino acids are either in a strongly immobilized regime or subjected to a fast motion
N111A
large decrease in reduction rate constant
N111D
large decrease in reduction rate constant. Reduction potential is about 100 mV lower than in wild-type
N172A
large decrease in reduction rate constant. Reduction potential is about 25 mV lower than in wild-type
N172A/N246A
large decrease in reduction rate constant. The maximum flavin absorbance is at 453 nm, blue-shifted 3 nm compared to wild type
N177A
large decrease in reduction rate constant. Reduction potential is about 25 mV lower than in wild-type
N246A
large decrease in reduction rate constant
S175A
-
very little activity
S175A
-
less than 0.01% of activity of the wild-type enzyme
S175A
-
mutation slows the rate of flavin reduction by 3 orders of magnitude. Reduction potential is about 40 mV lower than in wild-type
S175C
-
sufficient activity, catalysis and binding of dihydrooratate are affected
T178A
-
mutation slows the rate of flavin reduction by 3 orders of magnitude. Reduction potential is about 40 mV lower than in wild-type
T178S
-
reduction potential is about 25 mV lower than in wild-type
T178V
-
reduction potential is about 35 mV lower than in wild-type
Y2C/R1C
mutant incorporates into 1-dipalmitoyl-2-oleoyl-sn-glycero-3-phosphocholine/Triton X-100 mixed vesicles. Mutated residues experience a high degree of freedom that is compatible with their location in the beginning of the protein chain
Y318L
-
confocal fluorescence spectroscopy study
H11A
-
minimal effect on the relative enzyme activity
H122A
-
minimal effect on the relative enzyme activity
H129A
-
complete loss of enzymatic activity, conserved between the human and rat enzyme, required for enzymatic activity
H218A
-
minimal effect on the relative enzyme activity
H26A
-
minimal effect on the relative enzyme activity, insensitive against brequinar sodium inhibition, suggested location within the brequinar sodium binding pocket, important role in brequinar sodium binding to enzyme
H364A
-
complete loss of enzymatic activity, conserved between the human and rat enzyme, required for enzymatic activity
H56A
-
minimal effect on the relative enzyme activity
H71A
-
complete loss of enzymatic activity, surprising because no conserved residue in the closely related rat enzyme
S215C
-
increase of the average donor-acceptor distances for proton and hydride transfer and disruption of the hydrogen bonding pathways observed for the wild-type enzyme, significant decrease in enzyme activity
C130A
-
loss of activity
C130S
-
loss of activity
F188A
-
considerable changes in the binding affinities of the inhibitors without dramatically affecting the substrate binding affinities; kcat for reaction of L-dihydroorotate + decylubiquinone is 78% of the wild-type value. IC50-value for 2-cyano-3-(9-ethyl-9H-carbazol-3-ylamino)acrylic acid ethyl ester 513fold higher than wild-type value
F188A
-
mutation decreases the affinity for Plasmodium falciparum-specific inhibitors. Pre-steady state kinetic analysis
F188A
-
mutation has minimal effect on catalytic efficiency. IC50 value for inhibitor 5-methyl-N-(naphthalen-2-yl)[1,2,4]triazolo[1,5-a]pyrimidin-7-amine increases 30-50fold
F227A
-
mutation decreases the affinity for Plasmodium falciparum-specific inhibitors. Decrease in FMN content. Pre-steady state kinetic analysis
F227A
-
mutation has minimal effect on catalytic efficiency. IC50 value for inhibitor 5-methyl-N-(naphthalen-2-yl)[1,2,4]triazolo[1,5-a]pyrimidin-7-amine increases 30-50fold
H185A
-
4fold increase in KM-value of CoQD, 50% increase in KM-value of L-dihydroorotate
H185A
-
considerable changes in the binding affinities of the inhibitors without dramatically affecting the substrate binding affinities; kcat for reaction of L-dihydroorotate + decylubiquinone is 8.9% of the wild-type value. IC50-value for 2-cyano-3-(9-ethyl-9H-carbazol-3-ylamino)acrylic acid ethyl ester 775fold higher than wild-type value
H185A
-
mutation decreases the affinity for Plasmodium falciparum-specific inhibitors. Pre-steady state kinetic analysis
H185A
-
mutation has minimal effect on catalytic efficiency. IC50 value for inhibitor 5-methyl-N-(naphthalen-2-yl)[1,2,4]triazolo[1,5-a]pyrimidin-7-amine increases 30-50fold
I272A
-
decrease in FMN content. Pre-steady state kinetic analysis
R265A
-
2fold increase in KM-value of CoQD, 15% increase in KM-value of L-dihydroorotate
R265A
-
largest effect on Km for CoQ substrate among the mutants tested. Pre-steady state kinetic analysis
R265A
-
mutation has minimal effect on catalytic efficiency. IC50 value for inhibitor 5-methyl-N-(naphthalen-2-yl)[1,2,4]triazolo[1,5-a]pyrimidin-7-amine increases 30-50fold
R265K
-
considerable changes in the binding affinities of the inhibitors without dramatically affecting the substrate binding affinities; kcat for reaction of L-dihydroorotate + decylubiquinone is 102% of the wild-type value. IC50-value for 2-cyano-3-(9-ethyl-9H-carbazol-3-ylamino)acrylic acid ethyl ester 33.8fold higher than wild-type value
Y528A
-
substantial decrease in kcat value, decrease in FMN content. Pre-steady state kinetic analysis
Y528F
-
substantial decrease in kcat value, decrease in FMN content. Pre-steady state kinetic analysis
Y528W
-
substantial decrease in kcat value, decrease in FMN content. Pre-steady state kinetic analysis
DELTA1-29
-
deletion of N-terminal 29 amino acids
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
H71N
-
comparable activity to wild-type, taken together with the results for H71A mutant, the histidine residue is not required at this position, but this site is less permissive than most of the other histidine locations within the enzyme
additional information
-
substitution of all histidine residues by alanine
additional information
-
N-terminally truncated protein lacking first 29 amino acids
L531A
-
decrease in FMN content. Pre-steady state kinetic analysis
additional information
N-terminally truncated protein lacking 168 amino acids
additional information
-
deletion of a surface loop in PfDHODH containing amino acid residues 384-413, which facilitates crystallization of the enzyme with the triazolopyrimidine class of inhibitors. An N-terminal deletion that removes the mitochondrial membrane-spanning domain as well as residues that are N-terminal to this region does not lead to better crystal yields. Replacement of the thrombin site and T7 tag sequence in the vector with the TEV protease site
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
background for the development of antipyrimidines with high efficacy for decreasing in situ pyrimidine nucleotide pools in Candida albicans
medicine
-
molecular target of the antiproliferative, immunosuppressive compound brequinar sodium
medicine
-
enzyme inhibition is a mechanism of action that may be relevant for the therapeutic effects of leflunomide; great interest in inhibitors as potential therapeutic agents for the treatment of diseases involving aberrant cell proliferation
medicine
-
great interest in inhibitors as potential therapeutic agents for the treatment of diseases involving aberrant cell proliferation
medicine
-
-
medicine
-
development of small molecule inhibitors against DHODH
pharmacology
-
A77 1726 inhibits cell growth in multiple myeloma cell lines at clinically achievable concentrations by induction of apoptosis. Inhibition of cell growth is partly due to inhibition of multiple myeloma cell proliferation. A77 1726 shows synergistic and additive activity together with genotoxic agents melphalan, treosulfan, and doxorubicin
medicine
-
great interest in inhibitors as potential therapeutic agents for the treatment of diseases involving aberrant cell proliferation
drug development
-
DHODH represents a potential target for anti-malarial therapy
medicine
-
DHODH represents a potential target for anti-malarial therapy
drug development
-
DHODH represents a potential target for anti-malarial therapy
medicine
-
PfDHODH is a promising target for chemotherapeutic intervention in prevention of malaria; promising new target for chemotherapeutic intervention in prevention of malaria, synthesized inhibitors prevent growth of cultured parasites at low micromolar concentrations, interaction of inhibitors with amino acid residues F188, H185, and R265
medicine
-
DHODH represents a potential target for anti-malarial therapy
drug development
-
DHODH represents a potential target for anti-malarial therapy
medicine
-
DHODH represents a potential target for anti-malarial therapy
medicine
-
great interest in inhibitors as potential therapeutic agents for the treatment of diseases involving aberrant cell proliferation
medicine
-
-
medicine
-
inhibition of pyrimidine biosynthesis by targeting enzyme activity, mechanism for antimicrobial intervention
additional information
-
kinetic isotope effects on flavin reduction in anaerobic stopped-flow experiments, are about 3fold for DHO labeled at the 5-position, about 4fold for DHO labeled at the 6-position, and about 6-7fold for DHO labeled at both the 5- and 6-positions, at a pH value above the pKa controlling reduction, no isotope effect was observed for DHO deuterated at the 5-position, which is consistent with a stepwise reaction, above the kinetic pKa, the deprotonation of C5 is fast enough that it does not contribute to the observed rate constant and, therefore, is not isotopically sensitive
medicine
-
promising new target for chemotherapeutic intervention in prevention of malaria, synthesized inhibitors show considerable lower affinity for the human DHODH enzyme relative to the Plasmodium DHODH enzyme
additional information
-
kinetic isotope effects on flavin reduction in anaerobic stopped-flow experiments, pKa near 9.4 controlling reduction, similar to that previously reported for the Escherichia coli enzyme
additional information
-
three types of hydrogen bonding pathways, hydrogen bonding of the active base serine to a water molecule, which is hydrogen bonded to the substrate carboxylate group or a threonine residue, the threonine residue is positioned to enable proton transfer to another water molecule leading to the bulk solvent