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Information on EC 1.3.5.2 - dihydroorotate dehydrogenase (quinone) and Organism(s) Rattus norvegicus and UniProt Accession Q63707

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IUBMB Comments
This Class 2 dihydroorotate dehydrogenase enzyme contains FMN . The enzyme is found in eukaryotes in the mitochondrial membrane, in cyanobacteria, and in some Gram-negative and Gram-positive bacteria associated with the cytoplasmic membrane [2,5,6]. 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 . 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 . 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.
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Rattus norvegicus
UNIPROT: Q63707
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The taxonomic range for the selected organisms is: Rattus norvegicus
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
Synonyms
dihydroorotate dehydrogenase, pfdhodh, hdhodh, dho-dh, hsdhodh, dihydroorotate dehydrogenase (quinone), more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
(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
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
redox reaction
-
-
-
-
oxidation
-
-
-
-
reduction
-
-
-
-
PATHWAY SOURCE
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, in cyanobacteria, and in some Gram-negative and Gram-positive bacteria associated with the cytoplasmic membrane [2,5,6]. 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.
CAS REGISTRY NUMBER
COMMENTARY hide
59088-23-2
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
(S)-dihydroorotate + ubiquinone
orotate + ubiquinol
show the reaction diagram
dihydroorotate + acceptor
orotate + reduced acceptor
show the reaction diagram
-
-
-
?
(S)-dihydroorotate + decylubiquinone
orotate + decylubiquinol
show the reaction diagram
-
-
-
-
r
(S)-dihydroorotate + ubiquinone
orotate + reduced ubiquinone
show the reaction diagram
-
-
-
-
?
(S)-dihydroorotate + ubiquinone
orotate + ubiquinol
show the reaction diagram
dihydroorotate + acceptor
orotate + reduced acceptor
show the reaction diagram
L-dihydroorotate + 2,6-dihydrophenolindophenol
orotate + reduced 2,6-dihydrophenolindophenol
show the reaction diagram
-
-
-
-
r
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
(S)-dihydroorotate + ubiquinone
orotate + ubiquinol
show the reaction diagram
fourth enzyme in pyrimidine synthesis
-
ir
(S)-dihydroorotate + ubiquinone
orotate + ubiquinol
show the reaction diagram
dihydroorotate + acceptor
orotate + reduced acceptor
show the reaction diagram
-
fourth step in pyrimidine biosynthesis
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
additional information
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Iron
-
iron-zinc protein
Zinc
-
iron-zinc protein
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
brequinar sodium
complete activity termination in all tissues at 0.01 mM
toltrazuril
50% inhibition at 0.1 mM
1,10-phenanthroline
-
-
A77 1726
atovaquone
brequinar
brequinar sodium
dichloroallyl-lawsone
-
competitive to quinone
Lapachol
-
-
leflunomide
-
-
MNA 279
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malononitrilamide, 50% inhibition at 22-715 nM
MNA 715
-
malononitrilamide, 50% inhibition at 41-109 nM
redoxal
-
50% inhibition at 45-88 nM
Thenoyltrifluoroacetone
-
-
additional information
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.005
dihydroorotate
-
0.019
ubiquinone
-
0.0058
2,6-dihydrophenolindophenol
-
-
0.0095
decyclubiquinone
-
recombinant enzyme
0.0065 - 0.0095
decylubiquinone
0.015
dihydroorotate
-
recombinant enzyme
0.011 - 0.0146
S-dihydroorotate
0.007
ubiquinone
-
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
95
S-dihydroorotate
-
-
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.000698
atovaquone
-
-
0.00001
dichloro-allyllawsone
-
-
0.000061
Lapachol
-
-
0.049
Lawsone
-
-
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
130
-
expressed in SF21 insect cells
130 - 150
-
-
83
-
expressed in Escherichia coli
additional information
highest activities in ileum and colon
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.1
-
dihydroorotate + 2,6-dichlorophenolindophenol
8 - 8.1
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
regiospecific distribution of DHODH, immunohistochemic analysis, overview
Manually annotated by BRENDA team
-
high enzyme level
Manually annotated by BRENDA team
-
high level both of expression and activity
Manually annotated by BRENDA team
-
high level both of expression and activity
Manually annotated by BRENDA team
-
high level both of expression and activity
Manually annotated by BRENDA team
additional information
distribution in various tissues
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
metabolism
-
DHODH is the fourth enzyme in the biosynthesis of pyrimidines
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
PYRD_RAT
395
1
42663
Swiss-Prot
Secretory Pathway (Reliability: 4)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
45000
-
x * 45100, SDS-PAGE, recombinant from SF21 insect cells, x * 45000, SDS-PAGE, recombinant from Escherichia coli
45100
-
x * 45100, SDS-PAGE, recombinant from SF21 insect cells, x * 45000, SDS-PAGE, recombinant from Escherichia coli
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
monomer
-
folds into small N-terminal domain and an (alphabeta)8 barrel comprising the C-terminal domain, crystallization data
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
mutant DELTA1-29 in complex with brequinar and with atovaquone
-
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
DELTA1-29
-
deletion of N-terminal 29 amino acids
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-80°C, slight activity loss after freezing and storage
great inactivation by repeated thawing and freezing
-
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
Ni2+/nitrilotriacetate column
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
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
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Ullrich, A.; Knecht, W.; Fries, M.; Loffler, M.
Recombinant expression of N-terminal truncated mutants of the membrane bound mouse, rat and human flavoenzyme dihydroorotate dehydrogenase. A versatile tool to rate inhibitor effects?
Eur. J. Biochem.
268
1861-1868
2001
Homo sapiens, Mus musculus, Rattus norvegicus
Manually annotated by BRENDA team
Loeffler, M.; Becker, C.; Wegerle, E.; Schuster, G.
Catalytic enzyme histochemistry and biochemical analysis of dihydroorotate dehydrogenase/oxidase and succinate dehydrogenase in mammalian tissues, cells and mitochondria
Histochem. Cell Biol.
105
119-128
1996
Bos taurus, Cavia porcellus, Homo sapiens, Mus musculus, Rattus norvegicus (Q63707), Sus scrofa
Manually annotated by BRENDA team
Bader, B.; Knecht, W.; Fries, M.; Loffler, M.
Expression, purification, and characterization of histidine-tagged rat and human flavoenzyme dihydroorotate dehydrogenase
Protein Expr. Purif.
13
414-422
1998
Homo sapiens, Rattus norvegicus
Manually annotated by BRENDA team
Forman, H.J.; Kennedy, J.
Mammalian dihydroorotate dehydrogenase: physical and catalytic properties of the primary enzyme
Arch. Biochem. Biophys.
191
23-31
1978
Rattus norvegicus
Manually annotated by BRENDA team
Knecht, w.; Altekruse, D.; Rotgeri, A.; Gonski, S.; Loffler, M.
Rat dihydroorotate dehydrogenase: isolation of the recombinant enzyme from mitochondria of insect cells
Protein Expr. Purif.
10
89-99
1997
Rattus norvegicus (Q63707)
Manually annotated by BRENDA team
Knecht, W.; Henseling, J.; Loffler, M.
Kinetics of inhibition of human and rat dihydroorotate dehydrogenase by atovaquone, lawsone derivatives, brequinar sodium and polyporic acid
Chem. Biol. Interact.
124
61-76
2000
Homo sapiens, Rattus norvegicus
Manually annotated by BRENDA team
Hansen, M.; Le Nours, J.; Johansson, E.; Antal, T.; Ullrich, A.; Loffler, M.; Larsen, S.
Inhibitor binding in a class 2 dihydroorotate dehydrogenase causes variations in the membrane-associated N-terminal domain
Protein Sci.
13
1031-1042
2004
Rattus norvegicus
Manually annotated by BRENDA team
Schaefer, C.h.M.; Schaefer, M.K.; Loefflerr, M.
Region-specific distribution of dihydroorotate dehydrogenase in the rat central nervous system points to pyrimidine de novo synthesis in neurons
Nucleosides Nucleotides Nucleic Acids
29
476-481
2010
Rattus norvegicus
Manually annotated by BRENDA team
Hey-Mogensen, M.; Goncalves, R.L.; Orr, A.L.; Brand, M.D.
Production of superoxide/H2O2 by dihydroorotate dehydrogenase in rat skeletal muscle mitochondria
Free Radic. Biol. Med.
72
149-155
2014
Rattus norvegicus
Manually annotated by BRENDA team