1.3.5.2: dihydroorotate dehydrogenase (quinone)
This is an abbreviated version!
For detailed information about dihydroorotate dehydrogenase (quinone), go to the full flat file.
Word Map on EC 1.3.5.2
-
1.3.5.2
-
pyrimidine
-
falciparum
-
plasmodium
-
leflunomide
-
brequinar
-
uridine
-
malaria
-
arthritis
-
antimalarial
-
rheumatoid
-
dihydroorotase
-
salvage
-
teriflunomide
-
dhods
-
autoimmune
-
orotidine
-
ump
-
atovaquone
-
triazolopyrimidine
-
flavoenzyme
-
medicine
-
phosphoribosyltransferase
-
antirheumatic
-
coq
-
drug development
-
decylubiquinone
-
dmards
-
synthesis
-
species-selective
-
pyre
-
pharmacology
-
isoxazole
-
transcarbamoylase
-
5-fluoroorotate
- 1.3.5.2
- pyrimidine
- falciparum
- plasmodium
- leflunomide
- brequinar
- uridine
- malaria
- arthritis
-
antimalarial
-
rheumatoid
- dihydroorotase
-
salvage
- teriflunomide
-
dhods
- autoimmune
- orotidine
- ump
- atovaquone
- triazolopyrimidine
-
flavoenzyme
- medicine
-
phosphoribosyltransferase
-
antirheumatic
- coq
- drug development
- decylubiquinone
-
dmards
- synthesis
-
species-selective
-
pyre
- pharmacology
-
isoxazole
-
transcarbamoylase
- 5-fluoroorotate
Reaction
Synonyms
class 2 dihydroorotate dehydrogenases, DHO-DH, DHOD, DHODase, DHODH, dihydroorotate dehydrogenase, EC 1.3.99.11, ETH_00004975, hDHODH, HsDHODH, L-5,6-dihydroorotate:ubiquinone exidoreductase, PfDHODH
ECTree
1.3.5.2 dihydroorotate dehydrogenase (quinone)Advanced search results
results (
results (Engineering
Engineering on EC 1.3.5.2 - dihydroorotate dehydrogenase (quinone)
Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
top
PROTEIN VARIANTS 
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
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
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
S175A
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
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
H129A
-
complete loss of enzymatic activity, conserved between the human and rat enzyme, required for enzymatic 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
H71A
-
complete loss of enzymatic activity, surprising because no conserved residue in the closely related rat enzyme
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
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
F188A
F227A
H185A
I272A
decrease in FMN content. Pre-steady state kinetic analysis
L531A
decrease in FMN content. Pre-steady state kinetic analysis
R265A
R265K
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
N302S
additional information
S175A
-
mutation slows the rate of flavin reduction by 3 orders of magnitude. Reduction potential is about 40 mV lower than in wild-type
F188A
considerable changes in the binding affinities of the inhibitors without dramatically affecting the substrate binding affinities
F188A
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
H185A
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
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
R265K
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
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
additional information
-
N-terminally truncated protein lacking first 29 amino acids
additional information
expression of N-terminally truncated versions lacking the transmembrane anchor
additional information
-
expression of N-terminally truncated versions lacking the transmembrane anchor
additional information
N-terminally truncated protein lacking 168 amino acids
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
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
additional information
expression of N-terminally truncated versions lacking the transmembrane anchor
additional information
-
expression of N-terminally truncated versions lacking the transmembrane anchor
