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Information on EC 3.6.1.23 - dUTP diphosphatase and Organism(s) Plasmodium falciparum and UniProt Accession Q8II92
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3.6.1.23 dUTP diphosphataseIUBMB Comments
The enzyme catalyses the Mg2+-dependent hydrolysis of dUTP to dUMP, providing the substrate for EC 2.1.1.45, thymidylate synthase, leading to production of thymidine nucleotides. By reducing the effective ratio of dUTP to TTP, the enzyme also reduces the possibility of dUTP incorporation into DNA.
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Word Map
- 3.6.1.23
- uracil
- dump
- trimer
- thymidylate
-
misincorporation
- glycosylase
-
herpes
-
uracil-dna
- simplex
- drug development
-
homotrimeric
- herpesviruses
-
integrase
-
fluoropyrimidines
-
uracil-containing
- lentiviruses
- pyrophosphatases
-
sapis
-
ebv-encoded
- herv-k
- 2'-deoxyuridine
-
varicella-zoster
- fiv
- diagnostics
- medicine
- pharmacology
- synthesis
The taxonomic range for the selected organisms is: Plasmodium falciparum
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Synonyms
dutpase, deoxyuridine triphosphatase, deoxyuridine triphosphate nucleotidohydrolase, dut-n, deoxyuridine 5'-triphosphate nucleotidohydrolase, deoxyuridine 5'-triphosphate, dutp pyrophosphatase, dutp nucleotidohydrolase, orf 54, dcd-dut, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
desoxyuridine 5'-triphosphatase
-
-
-
-
desoxyuridine 5'-triphosphate nucleotidohydrolase
-
-
-
-
desoxyuridine-triphosphatase
-
-
-
-
dUTP pyrophosphatase
dUTPase
P18
-
-
-
-
PIP4
-
-
-
-
dUTP pyrophosphatase
-
-
-
-
dUTPase
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
phosphorous acid anhydride hydrolysis
-
-
-
-
PATHWAY SOURCE
PATHWAYS
BRENDA
-
-, -, -, -, -
SYSTEMATIC NAME
IUBMB Comments
dUTP nucleotidohydrolase
The enzyme catalyses the Mg2+-dependent hydrolysis of dUTP to dUMP, providing the substrate for EC 2.1.1.45, thymidylate synthase, leading to production of thymidine nucleotides. By reducing the effective ratio of dUTP to TTP, the enzyme also reduces the possibility of dUTP incorporation into DNA.
CAS REGISTRY NUMBER
COMMENTARY
37289-34-2
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
2'-deoxy-5-fluoro-UTP + H2O
2'-deoxy-5-fluoro-UMP + diphosphate
-
most specific substrate
-
-
?
dUTP + H2O
dUMP + diphosphate
-
-
-
-
?
dUTP + H2O
dUMP + diphosphate
-
the enzyme is highly specific for dUTP
-
-
?
dUTP + H2O
dUMP + diphosphate
-
the enzyme has two major roles in maintaining the correct free nucleotide balance in the cell. It provides dUMP, a major cellular source for dTMP which is in turn needed for dTTP formation. It also maintains the concentration of dUTP lower than that of dTTP thereby minimizing mistaken incorporation of dUTP into DNA
-
-
?
dUTP + H2O
dUMP + diphosphate
-
dUTPase catalyzes the hydrolysis of the alpha,beta-diphosphate bond of dUTP
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
dUTP + H2O
dUMP + diphosphate
-
the enzyme has two major roles in maintaining the correct free nucleotide balance in the cell. It provides dUMP, a major cellular source for dTMP which is in turn needed for dTTP formation. It also maintains the concentration of dUTP lower than that of dTTP thereby minimizing mistaken incorporation of dUTP into DNA
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Co2+
-
can substitute the physiological cofactor Mg2+, however the kcat is significantly reduced compared to dUTP-Mg2+
Mg2+
Mn2+
-
can substitute the physiological cofactor Mg2+, however the kcat is significantly reduced compared to dUTP-Mg2+
Mg2+
-
dependent on, the energetic barrier of the reaction is 4fold higher when Mg2+ is depleted
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
1-[(2E)-4-(trityloxy)but-2-en-1-yl]pyrimidine-2,4(1H,3H)-dione
-
1-[(2R,5S)-5-([[tert-butyl(diphenyl)silyl]oxy]methyl)-2,5-dihydrofuran-2-yl]pyrimidine-2,4(1H,3H)-dione
-
1-[(2R,5S)-5-[(trityloxy)methyl]-2,5-dihydrofuran-2-yl]pyrimidine-2,4(1H,3H)-dione
-
1-[2-(carbobenzoxymethyl)-4-(triphenylmethyl)aminobutyl]uracil
-
1-[2-(diethylamido)-4-(tert-butyldiphenylsilyloxy)butyl]uracil
-
1-[2-(N-benzyloxycarbonylpiperazinamido)-4-(tert-butyldiphenylsilyloxy)butyl]uracil
-
1-[2-(tert-butyldiphenylsilyloxyethylamido)-4-trityloxybutyl]uracil
-
1-[4-hydroxy-3-[(tritylamino)methyl]butyl]pyrimidine-2,4(1H,3H)-dione
-
1-[3-(benzhydrylaminocarbonyl)propyl]uracil
-
1429fold selectivity over human enzyme
1-[3-(tritylaminocarbonyl)propyl]uracil
-
4545fold selectivity over human enzyme
2',3',5'-trideoxy-3'-fluoro-5'-(tritylamino)uridine
-
activity against the parasites with IC50: 0.0053 mM
2',3'-dideoxy-3'-fluoro-5'-O-trityluridine
-
activity against the parasites with IC50: 0.0020 mM, binding structure involving Tyr112, Ile117, Ile108, and Asn103, overview
2',5'-dideoxy-5'-(tritylamino)uridine
-
activity against the parasites with IC50: 0.0045 mM
2'-deoxy-5'-O-(triphenylsilyl)uridine
-
activity against the parasites with IC50: 0.0011 mM
2'-deoxy-5'-O-trityluridine
-
activity against the parasites with IC50: 0.006 mM
2'-deoxy-5'-O-[tris(1-methylethoxy)silyl]uridine
-
activity against the parasites with IC50: 0.013 mM
3'-O-tert-butyldimethylsilyl-2',5'-dideoxyuridine 5'-N-diphenylphosphoramidate
-
-
EDTA
-
causes a 105fold decrease and a 12fold increase of the kcat and Km values for dUTP hydrolysis, respectively, compared to the dUTP-Mg2+ complex
additional information
-
growth inhibition potency in vitro, overview, molecular docking modeling study
-
additional information
-
inhibitor in vivo activity against the parasite, overview
-
additional information
-
design and synthesis of tert-butyl diphenyl silyl uracil acetamides inhibitors, molecular modelling, overview
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.00173
2'-deoxy-5-fluoro-UTP
-
at 25°C in 25 mM MES, 5 mM NaCl, 25 mM MgCl2, 1 mM beta-mercaptoethanol, at pH 7.0
0.438
beta-L-2'-dUTP
-
at 25°C in 25 mM MES, 5 mM NaCl, 25 mM MgCl2, 1 mM beta-mercaptoethanol, at pH 7.0
1.13
dATP
-
at 25°C in 25 mM MES, 5 mM NaCl, 25 mM MgCl2, 1 mM beta-mercaptoethanol, at pH 7.0
0.465
dCTP
-
at 25°C in 25 mM MES, 5 mM NaCl, 25 mM MgCl2, 1 mM beta-mercaptoethanol, at pH 7.0
1.96
dGTP
-
at 25°C in 25 mM MES, 5 mM NaCl, 25 mM MgCl2, 1 mM beta-mercaptoethanol, at pH 7.0
0.29
dTTP
-
at 25°C in 25 mM MES, 5 mM NaCl, 25 mM MgCl2, 1 mM beta-mercaptoethanol, at pH 7.0
0.571
UTP
-
at 25°C in 25 mM MES, 5 mM NaCl, 25 mM MgCl2, 1 mM beta-mercaptoethanol, at pH 7.0
additional information
additional information
-
Michaelis-Menten and ligand binding kinetics, overview. Thermodynamic parameters for the interaction between Plasmodium falciparum dUTPase and deoxyuridine derivatives at 25.2 °C and pH 7.0
-
0.00187
dUTP
-
at 25°C in 25 mM MES, 5 mM NaCl, 25 mM MgCl2, 1 mM beta-mercaptoethanol, at pH 7.0
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
110
2'-deoxy-5-fluoro-UTP
-
at 25°C in 25 mM MES, 5 mM NaCl, 25 mM MgCl2, 1 mM beta-mercaptoethanol, at pH 7.0
0.00525
beta-L-2'-dUTP
-
at 25°C in 25 mM MES, 5 mM NaCl, 25 mM MgCl2, 1 mM beta-mercaptoethanol, at pH 7.0
0.00265
dATP
-
at 25°C in 25 mM MES, 5 mM NaCl, 25 mM MgCl2, 1 mM beta-mercaptoethanol, at pH 7.0
0.02172
dCTP
-
at 25°C in 25 mM MES, 5 mM NaCl, 25 mM MgCl2, 1 mM beta-mercaptoethanol, at pH 7.0
0.00013
dGTP
-
at 25°C in 25 mM MES, 5 mM NaCl, 25 mM MgCl2, 1 mM beta-mercaptoethanol, at pH 7.0
0.0092
dTTP
-
at 25°C in 25 mM MES, 5 mM NaCl, 25 mM MgCl2, 1 mM beta-mercaptoethanol, at pH 7.0
7100
dUTP
-
at 25°C in 25 mM MES, 5 mM NaCl, 25 mM MgCl2, 1 mM beta-mercaptoethanol, at pH 7.0
0.01121
UTP
-
at 25°C in 25 mM MES, 5 mM NaCl, 25 mM MgCl2, 1 mM beta-mercaptoethanol, at pH 7.0
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0013
1-(2-amido-4-trityloxybutyl)uracil
pH and temperature not specified in the publication
0.0027
1-(2-dimethylamido-4-trityloxybutyl)uracil
pH and temperature not specified in the publication
0.0021
1-(2-morpholinamido-4-trityloxybutyl)uracil
pH and temperature not specified in the publication
0.00021 - 0.017
1-[(2R,5S)-5-([[tert-butyl(diphenyl)silyl]oxy]methyl)-2,5-dihydrofuran-2-yl]pyrimidine-2,4(1H,3H)-dione
0.00039 - 0.0203
1-[(2R,5S)-5-[(trityloxy)methyl]-2,5-dihydrofuran-2-yl]pyrimidine-2,4(1H,3H)-dione
0.005
1-[2-(acetamido)-4-(tert-butyldiphenylsilyloxy)butyl]uracil
pH and temperature not specified in the publication
0.0055
1-[2-(acetamido)-4-(triphenylmethyl)aminobutyl]uracil
pH and temperature not specified in the publication
0.0065
1-[2-(carbobenzoxymethyl)-4-(triphenylmethyl)aminobutyl]uracil
pH and temperature not specified in the publication
0.0005
1-[2-(carboethoxyethylamido)-4-trityloxybutyl]uracil
pH and temperature not specified in the publication
0.0016
1-[2-(carboxy)-4-(tert-butyldiphenylsilyloxy)butyl]uracil
pH and temperature not specified in the publication
0.0072
1-[2-(carboxy)-4-(triphenylmethyl)aminobutyl]uracil
pH and temperature not specified in the publication
0.0002
1-[2-(carboxyethylamido)-4-trityloxybutyl]uracil
pH and temperature not specified in the publication
0.02
1-[2-(diethylamido)-4-(tert-butyldiphenylsilyloxy)butyl]uracil
pH and temperature not specified in the publication
0.0057
1-[2-(ethylamido)-4-(tert-butyldiphenylsilyloxy) butyl]uracil
pH and temperature not specified in the publication
0.0004
1-[2-(hydroxyethylamido)-4-trityloxybutyl]uracil
pH and temperature not specified in the publication
0.0014
1-[2-(methoxyethylamido)-4-trityloxybutyl]uracil
pH and temperature not specified in the publication
0.0036
1-[2-(methylamido)-4-(tert-butyldiphenylsilyloxy)butyl]uracil
pH and temperature not specified in the publication
0.0078
1-[2-(N,N-dimethylaminoethylamido)-4-trityloxybutyl]uracil
pH and temperature not specified in the publication
0.098
1-[2-(N-benzyloxycarbonylpiperazinamido)-4-(tert-butyldiphenylsilyloxy)butyl]uracil
pH and temperature not specified in the publication
0.0056
1-[2-(N-methylpiperazine)amido-4-trityloxybutyl]uracil
pH and temperature not specified in the publication
0.01
1-[2-(tert-butyldiphenylsilyloxyethylamido)-4-trityloxybutyl]uracil
Ki above 0.01 mM, pH and temperature not specified in the publication
0.0007
1-[3-(benzhydrylaminocarbonyl)propyl]uracil
-
pH 8.0, temperature not specified in the publication
0.0002
1-[3-(tritylaminocarbonyl)propyl]uracil
-
pH 8.0, temperature not specified in the publication
0.0025
1-[4-(tert-butoxycarbonylamino)-3-(trityloxymethyl)butyl]uracil
-
-
1
1-[N-(triphenylmethylaminoethyl)-N-(aminoethyl) acetamide]uracil
-
above
1
1-[N-hydroxyethyl-N-(triphenylmethylamino) ethyl-acetamide]uracil
-
above
0.0125
2',3',5'-trideoxy-3'-fluoro-5'-(tritylamino)uridine
-
pH 5.7-6.2, recombinant enzyme
0.005
2',3'-dideoxy-3'-fluoro-5'-O-trityluridine
-
pH 5.7-6.2, recombinant enzyme
0.0002
2',5'-dideoxy-5'-(tritylamino)uridine
-
pH 5.7-6.2, recombinant enzyme
0.0028
2'-deoxy-5'-O-(triphenylsilyl)uridine
-
pH 5.7-6.2, recombinant enzyme
0.2271
2'-deoxy-5'-O-[tris(1-methylethoxy)silyl]uridine
-
pH 5.7-6.2, recombinant enzyme
0.067
3'-O-tert-butyldimethylsilyl-2',5'-dideoxyuridine 5'-N-diphenylphosphoramidate
-
-
1
N-[3-(tert-butyl diphenyl silanyloxy)-propyl]-2-uracil acetamide
-
above
1
N-[4-(tert-butyl diphenyl silanyloxy)-butyl]-2-uracil acetamide
-
above
0.00009
1-[(2E)-4-(trityloxy)but-2-en-1-yl]pyrimidine-2,4(1H,3H)-dione
mutant enzyme K96A, at pH 8.0 and 25°
0.0006
1-[(2E)-4-(trityloxy)but-2-en-1-yl]pyrimidine-2,4(1H,3H)-dione
wild type enzyme, at pH 8.0 and 25°
0.0008
1-[(2E)-4-(trityloxy)but-2-en-1-yl]pyrimidine-2,4(1H,3H)-dione
mutant enzyme I117A, at pH 8.0 and 25°
0.006
1-[(2E)-4-(trityloxy)but-2-en-1-yl]pyrimidine-2,4(1H,3H)-dione
mutant enzyme F46A, at pH 8.0 and 25°
0.00021
1-[(2R,5S)-5-([[tert-butyl(diphenyl)silyl]oxy]methyl)-2,5-dihydrofuran-2-yl]pyrimidine-2,4(1H,3H)-dione
mutant enzyme K96A, at pH 8.0 and 25°
0.0008
1-[(2R,5S)-5-([[tert-butyl(diphenyl)silyl]oxy]methyl)-2,5-dihydrofuran-2-yl]pyrimidine-2,4(1H,3H)-dione
mutant enzyme I117A, at pH 8.0 and 25°
0.0012
1-[(2R,5S)-5-([[tert-butyl(diphenyl)silyl]oxy]methyl)-2,5-dihydrofuran-2-yl]pyrimidine-2,4(1H,3H)-dione
wild type enzyme, at pH 8.0 and 25°
0.017
1-[(2R,5S)-5-([[tert-butyl(diphenyl)silyl]oxy]methyl)-2,5-dihydrofuran-2-yl]pyrimidine-2,4(1H,3H)-dione
mutant enzyme F46A, at pH 8.0 and 25°
0.00039
1-[(2R,5S)-5-[(trityloxy)methyl]-2,5-dihydrofuran-2-yl]pyrimidine-2,4(1H,3H)-dione
mutant enzyme K96A, at pH 8.0 and 25°
0.0016
1-[(2R,5S)-5-[(trityloxy)methyl]-2,5-dihydrofuran-2-yl]pyrimidine-2,4(1H,3H)-dione
mutant enzyme I117A, at pH 8.0 and 25°
0.0019
1-[(2R,5S)-5-[(trityloxy)methyl]-2,5-dihydrofuran-2-yl]pyrimidine-2,4(1H,3H)-dione
wild type enzyme, at pH 8.0 and 25°
0.0203
1-[(2R,5S)-5-[(trityloxy)methyl]-2,5-dihydrofuran-2-yl]pyrimidine-2,4(1H,3H)-dione
mutant enzyme F46A, at pH 8.0 and 25°
0.00004
1-[3-(tritylamino)propyl]pyrimidine-2,4(1H,3H)-dione
mutant enzyme K96A, at pH 8.0 and 25°
0.0002
1-[3-(tritylamino)propyl]pyrimidine-2,4(1H,3H)-dione
wild type enzyme, at pH 8.0 and 25°
0.0006
1-[3-(tritylamino)propyl]pyrimidine-2,4(1H,3H)-dione
mutant enzyme I117A, at pH 8.0 and 25°
0.028
1-[3-(tritylamino)propyl]pyrimidine-2,4(1H,3H)-dione
mutant enzyme F46A, at pH 8.0 and 25°
0.00004
1-[4-hydroxy-3-[(tritylamino)methyl]butyl]pyrimidine-2,4(1H,3H)-dione
mutant enzyme K96A, at pH 8.0 and 25°
0.0002
1-[4-hydroxy-3-[(tritylamino)methyl]butyl]pyrimidine-2,4(1H,3H)-dione
wild type enzyme, at pH 8.0 and 25°
0.00027
1-[4-hydroxy-3-[(tritylamino)methyl]butyl]pyrimidine-2,4(1H,3H)-dione
mutant enzyme I117A, at pH 8.0 and 25°
0.029
1-[4-hydroxy-3-[(tritylamino)methyl]butyl]pyrimidine-2,4(1H,3H)-dione
mutant enzyme F46A, at pH 8.0 and 25°
0.00015
1-[6-(tritylamino)hexyl]pyrimidine-2,4(1H,3H)-dione
mutant enzyme K96A, at pH 8.0 and 25°
0.0018
1-[6-(tritylamino)hexyl]pyrimidine-2,4(1H,3H)-dione
wild type enzyme, at pH 8.0 and 25°
0.0044
1-[6-(tritylamino)hexyl]pyrimidine-2,4(1H,3H)-dione
mutant enzyme I117A, at pH 8.0 and 25°
0.035
1-[6-(tritylamino)hexyl]pyrimidine-2,4(1H,3H)-dione
mutant enzyme F46A, at pH 8.0 and 25°
0.0007
1-[[2-(trityloxy)ethoxy]methyl]pyrimidine-2,4(1H,3H)-dione
wild type enzyme, at pH 8.0 and 25°
0.008
1-[[2-(trityloxy)ethoxy]methyl]pyrimidine-2,4(1H,3H)-dione
mutant enzyme I117A, at pH 8.0 and 25°
0.013
1-[[2-(trityloxy)ethoxy]methyl]pyrimidine-2,4(1H,3H)-dione
mutant enzyme F46A, at pH 8.0 and 25°
0.0048
2',3'-dideoxy-3'-fluoro-5'-O-trityluridine
mutant enzyme K96A, at pH 8.0 and 25°
0.005
2',3'-dideoxy-3'-fluoro-5'-O-trityluridine
wild type enzyme, at pH 8.0 and 25°
0.225
2',3'-dideoxy-3'-fluoro-5'-O-trityluridine
mutant enzyme F46A, at pH 8.0 and 25°
0.406
2',3'-dideoxy-3'-fluoro-5'-O-trityluridine
mutant enzyme I117A, at pH 8.0 and 25°
0.00011
2',5'-dideoxy-5'-(tritylamino)uridine
mutant enzyme K96A, at pH 8.0 and 25°
0.00024
2',5'-dideoxy-5'-(tritylamino)uridine
wild type enzyme, at pH 8.0 and 25°
0.0013
2',5'-dideoxy-5'-(tritylamino)uridine
mutant enzyme I117A, at pH 8.0 and 25°
0.02
2',5'-dideoxy-5'-(tritylamino)uridine
mutant enzyme F46A, at pH 8.0 and 25°
0.121
dUTP
-
pH 7.0, 25°C, recombinant enzyme, without NaCl, presence of EDTA
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0039
1-[N-(triphenylmethyl) diaminodi(n-propyl) acetamide]uracil
Plasmodium falciparum
-
above
0.0045
1-[N-(triphenylmethylaminoethyl)-N-(aminoethyl) acetamide]uracil
Plasmodium falciparum
-
above
0.083
1-[N-hydroxyethyl-N-(triphenylmethylamino) ethyl-acetamide]uracil
Plasmodium falciparum
-
above
0.0053
2',3',5'-trideoxy-3'-fluoro-5'-(tritylamino)uridine
Plasmodium falciparum
-
activity against the parasites with IC50: 0.0053 mM
0.002
2',3'-dideoxy-3'-fluoro-5'-O-trityluridine
Plasmodium falciparum
-
activity against the parasites with IC50: 0.0020 mM, binding structure involving Tyr112, Ile117, Ile108, and Asn103, overview
0.0045
2',5'-dideoxy-5'-(tritylamino)uridine
Plasmodium falciparum
-
activity against the parasites with IC50: 0.0045 mM
0.0011
2'-deoxy-5'-O-(triphenylsilyl)uridine
Plasmodium falciparum
-
activity against the parasites with IC50: 0.0011 mM
0.006
2'-deoxy-5'-O-trityluridine
Plasmodium falciparum
-
activity against the parasites with IC50: 0.006 mM
0.013
2'-deoxy-5'-O-[tris(1-methylethoxy)silyl]uridine
Plasmodium falciparum
-
activity against the parasites with IC50: 0.013 mM
0.0046
N-[3-(tert-butyl diphenyl silanyloxy)-propyl]-2-uracil acetamide
Plasmodium falciparum
-
above
0.0037
N-[4-(tert-butyl diphenyl silanyloxy)-butyl]-2-uracil acetamide
Plasmodium falciparum
-
above
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pI VALUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
physiological function
the enzyme is involved in nucleotide metabolism that acts as first line of defence against uracil incorporation into DNA
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
trimer
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
purified recombinant enzyme in complex with inhibitor 2',3'-dideoxy-3'-fluoro-5'-O-trityluridine, X-ray diffraction structure determination and analysis at 2.4 A resolution
-
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
F46A
the mutation does not affect the nucleotide hydrolase activity of dUTPase
I117A
the mutation does not affect the nucleotide hydrolase activity of dUTPase
K96A
the mutation does not affect the nucleotide hydrolase activity of dUTPase
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
phosphocellulose column chromatography and Superdex 200 gel filtration
recombinant enzyme from Escherichia coli by phosphocellulose chromatography and gel filtration to near homogeneity
-
recombinant enzyme from Escherichia coli strain BL21(DE3) by cation exchange chromatography, gel filtration, and anion exchange chromatography to near homogeneity
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expressed in Escherichia coli BL21(DE3) cells
DNA and amino acid sequence determination and analysis, the gene locates on chromosome 11, overexpression in Escherichia coli strain BL21(DE3)
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
drug development
drug development
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dUTPase as a platform for antimalarial drug design: structural basis for the selectivity of a class of nucleoside inhibitors
drug development
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the enzyme is a potential drug target against malaria
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Nguyen, C.; Kasinathan, G.; Leal-Cortijo, I.; Musso-Buendia, A.; Kaiser, M.; Brun, R.; Ruiz-Perez, L.M.; Johansson, N.G.; Gonzalez-Pacanowska, D.; Gilbert, I.H.
Deoxyuridine triphosphate nucleotidohydrolase as a potential antiparasitic drug target
J. Med. Chem.
48
5942-5954
2005
Homo sapiens, Leishmania donovani, Leishmania major, Plasmodium falciparum
Nguyen, C.; Ruda, G.F.; Schipani, A.; Kasinathan, G.; Leal, I.; Musso-Buendia, A.; Kaiser, M.; Brun, R.; Ruiz-Perez, L.M.; Sahlberg, B.L.; Johansson, N.G.; Gonzalez-Pacanowska, D.; Gilbert, I.H.
Acyclic nucleoside analogues as inhibitors of Plasmodium falciparum dUTPase
J. Med. Chem.
49
4183-4195
2006
Homo sapiens, Plasmodium falciparum
Whittingham, J.L.; Leal, I.; Nguyen, C.; Kasinathan, G.; Bell, E.; Jones, A.F.; Berry, C.; Benito, A.; Turkenburg, J.P.; Dodson, E.J.; Perez, L.M.; Wilkinson, A.J.; Johansson, N.G.; Brun, R.; Gilbert, I.H.; Pacanowska, D.G.; Wilson, K.S.
dUTPase as a platform for antimalarial drug design: structural basis for the selectivity of a class of nucleoside inhibitors
Structure
13
329-338
2005
Plasmodium falciparum
Quesada-Soriano, I.; Leal, I.; Casas-Solvas, J.M.; Vargas-Berenguel, A.; Baron, C.; Ruiz-Perez, L.M.; Gonzalez-Pacanowska, D.; Garcia-Fuentes, L.
Kinetic and thermodynamic characterization of dUTP hydrolysis by Plasmodium falciparum dUTPase
Biochim. Biophys. Acta
1784
1347-1355
2008
Plasmodium falciparum
McCarthy, O.; Musso-Buendia, A.; Kaiser, M.; Brun, R.; Ruiz-Perez, L.M.; Johansson, N.G.; Pacanowska, D.G.; Gilbert, I.H.
Design, synthesis and evaluation of novel uracil acetamide derivatives as potential inhibitors of Plasmodium falciparum dUTP nucleotidohydrolase
Eur. J. Med. Chem.
44
678-688
2009
Plasmodium falciparum
Quesada-Soriano, I.; Casas-Solvas, J.M.; Recio, E.; Ruiz-Perez, L.M.; Vargas-Berenguel, A.; Gonzalez-Pacanowska, D.; Garcia-Fuentes, L.
Kinetic properties and specificity of trimeric Plasmodium falciparum and human dUTPases
Biochimie
92
178-186
2010
Homo sapiens, Plasmodium falciparum
Baragana, B.; McCarthy, O.; Sanchez, P.; Bosch-Navarrete, C.; Kaiser, M.; Brun, R.; Whittingham, J.L.; Roberts, S.M.; Zhou, X.X.; Wilson, K.S.; Johansson, N.G.; Gonzalez-Pacanowska, D.; Gilbert, I.H.
beta-Branched acyclic nucleoside analogues as inhibitors of Plasmodium falciparum dUTPase
Bioorg. Med. Chem.
19
2378-2391
2011
Plasmodium falciparum (Q8II92), Plasmodium falciparum
Recio, E.; Musso-Buendia, A.; Vidal, A.E.; Ruda, G.F.; Kasinathan, G.; Nguyen, C.; Ruiz-Perez, L.M.; Gilbert, I.H.; Gonzalez-Pacanowska, D.
Site-directed mutagenesis provides insights into the selective binding of trityl derivatives to Plasmodium falciparum dUTPase
Eur. J. Med. Chem.
46
3309-3314
2011
Plasmodium falciparum (Q8II92), Plasmodium falciparum
Hampton, S.E.; Schipani, A.; Bosch-Navarrete, C.; Recio, E.; Kaiser, M.; Kahnberg, P.; Gonzalez-Pacanowska, D.; Johansson, N.G.; Gilbert, I.H.
Investigation of acyclic uridine amide and 5-amido nucleoside analogues as potential inhibitors of the Plasmodium falciparum dUTPase
Bioorg. Med. Chem.
21
5876-5885
2013
Plasmodium falciparum
Hizi, A.; Herzig, E.
dUTPase the frequently overlooked enzyme encoded by many retroviruses
Retrovirology
12
70
2015
bovine immunodeficiency virus, Caenorhabditis elegans, Caprine arthritis encephalitis virus, equine infectious anemia virus, Escherichia coli (P06968), feline immunodeficiency virus, Homo sapiens (P33316), Homo sapiens, Human endogenous retrovirus K, Human gammaherpesvirus 4, Human gammaherpesvirus 8, Jembrana disease virus, Mason-Pfizer monkey virus, mouse mammary tumor virus, Murid gammaherpesvirus 4, Mycobacterium tuberculosis, Plasmodium falciparum, Saccharomyces cerevisiae, Visna-maedi virus
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