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Information on EC 3.6.1.23 - dUTP diphosphatase and Organism(s) Saccharomyces cerevisiae and UniProt Accession P33317
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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: Saccharomyces cerevisiae
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, deoxyuridine 5'-triphosphate nucleotidohydrolase, dut-n, 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
-
-
-
-
additional information
-
the enzyme belongs to the Nudix superfamily of enzymes
dUTPase
-
-
-
-
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
dUTP + H2O = dUMP + diphosphate
structural organization and substrate binding modes
-
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
dITP + H2O
dIMP + diphosphate
shows also significant activity against dITP
-
-
?
UTP + H2O
UMP + diphosphate
substrate for mutant enzyme Y88A
-
-
?
dUTP + H2O
dUMP + diphosphate
-
removes dUTP from the nucleotide triphosphate pool and therefore prevents the incorporation of uracil into the DNA
-
-
?
additional information
?
-
alpha,beta-imido dUTP is a non-hydrolysable substrate
-
-
?
additional information
?
-
-
alpha,beta-imido dUTP is a non-hydrolysable substrate
-
-
?
additional information
?
-
-
biological functions in housekeeping, overview
-
-
?
additional information
?
-
-
substrate specificity, no hydrolysis of canonical NTPs, overview
-
-
?
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
additional information
?
-
-
biological functions in housekeeping, overview
-
-
?
dUTP + H2O
dUMP + diphosphate
-
removes dUTP from the nucleotide triphosphate pool and therefore prevents the incorporation of uracil into the DNA
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Mg2+
strictly dependent on a bivalent metal cation like Mg2+ which supports the highest rate of dUTP hydrolysis
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0447
dITP
wild type enzyme, in 50 mM HEPES (pH 7.5), 5 mM MgCl2, 1 mM MnCl2, 0.5 mM NiCl2, at 30°C
0.035
UTP
mutant enzyme Y88A, in 50 mM HEPES (pH 7.5), 5 mM MgCl2, 1 mM MnCl2, 0.5 mM NiCl2, at 30°C
0.0132
dUTP
wild type enzyme, in 50 mM HEPES (pH 7.5), 5 mM MgCl2, 1 mM MnCl2, 0.5 mM NiCl2, at 30°C
0.0142
dUTP
mutant enzyme Q114A, in 50 mM HEPES (pH 7.5), 5 mM MgCl2, 1 mM MnCl2, 0.5 mM NiCl2, at 30°C
0.0315
dUTP
mutant enzyme R111A, in 50 mM HEPES (pH 7.5), 5 mM MgCl2, 1 mM MnCl2, 0.5 mM NiCl2, at 30°C
0.041
dUTP
mutant enzyme Y88A, in 50 mM HEPES (pH 7.5), 5 mM MgCl2, 1 mM MnCl2, 0.5 mM NiCl2, at 30°C
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
1.3
dITP
wild type enzyme, in 50 mM HEPES (pH 7.5), 5 mM MgCl2, 1 mM MnCl2, 0.5 mM NiCl2, at 30°C
5.3
UTP
mutant enzyme Y88A, in 50 mM HEPES (pH 7.5), 5 mM MgCl2, 1 mM MnCl2, 0.5 mM NiCl2, at 30°C
1.3
dUTP
mutant enzyme Q114A, in 50 mM HEPES (pH 7.5), 5 mM MgCl2, 1 mM MnCl2, 0.5 mM NiCl2, at 30°C
3.3
dUTP
mutant enzyme R111A, in 50 mM HEPES (pH 7.5), 5 mM MgCl2, 1 mM MnCl2, 0.5 mM NiCl2, at 30°C
7.4
dUTP
mutant enzyme Y88A, in 50 mM HEPES (pH 7.5), 5 mM MgCl2, 1 mM MnCl2, 0.5 mM NiCl2, at 30°C
9.6
dUTP
wild type enzyme, in 50 mM HEPES (pH 7.5), 5 mM MgCl2, 1 mM MnCl2, 0.5 mM NiCl2, at 30°C
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
29
dITP
wild type enzyme, in 50 mM HEPES (pH 7.5), 5 mM MgCl2, 1 mM MnCl2, 0.5 mM NiCl2, at 30°C
150
UTP
mutant enzyme Y88A, in 50 mM HEPES (pH 7.5), 5 mM MgCl2, 1 mM MnCl2, 0.5 mM NiCl2, at 30°C
90
dUTP
mutant enzyme Q114A, in 50 mM HEPES (pH 7.5), 5 mM MgCl2, 1 mM MnCl2, 0.5 mM NiCl2, at 30°C
100
dUTP
mutant enzyme R111A, in 50 mM HEPES (pH 7.5), 5 mM MgCl2, 1 mM MnCl2, 0.5 mM NiCl2, at 30°C
180
dUTP
mutant enzyme Y88A, in 50 mM HEPES (pH 7.5), 5 mM MgCl2, 1 mM MnCl2, 0.5 mM NiCl2, at 30°C
740
dUTP
wild type enzyme, in 50 mM HEPES (pH 7.5), 5 mM MgCl2, 1 mM MnCl2, 0.5 mM NiCl2, at 30°C
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
physiological function
the enzyme plays a key role in preventing uracil incorporation into DNA
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
18100
3 * 18100, His tagged enzyme, calculated from amino acid sequence
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
homotrimer
3 * 18100, His tagged enzyme, calculated from amino acid sequence
hexamer
-
composed of two identical trimers, crystal structure analysis
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
hanging drop vapor diffusion method, apo-enzyme using 0.1 M ammonium sulfate, 0.1 M Bis-Tris (pH 5.5), and 25% (w/v) PEG3350. In complex with dUMP using 0.2 M sodium acetate, 0.1 M Tris-HCl (pH 8.5), and 30% (w/v) PEG4000. In complex with alpha,beta-imido dUTP using 30% Jeffamine ED-2001 (pH 7.0), 0.1 M potassium-HEPES (pH 7.0) and 3 mM MgCl2
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
G82S
allele dut1-1 of gene dut1 possesses a single amino acid substitution in a conserved motif nearby the active site and exhibits a greatly reduced dUTPase activity, dut1-1 single mutant exhibits growth delay and cell cycle abnormalities and shows a strong spontaneous mutator phenotype, the dut1-1 allele is deleterious in wild-type strain and AP sites repair defective mutants, overview. The dut1-1 mutant is a spontaneous mutator that accumulates AT to CG transversions
Q114A
the mutant shows essentially the wild type affinity for dUTP and greatly reduced activity
R111A
the mutant has reduced activity and lower substrate affinity (increased Km) compared to the wild type enzyme
Y88A
the mutant protein is equally active against both dUTP and UTP and has reduced activity and lower substrate affinity (increased Km) compared to the wild type enzyme
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
nickel affinity resin column chromatography and Superdex-200 gel filtration
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
gene DUT1, DNA and amino acid sequence determination and analysis of DUT1 alleles, genotyping, expression of wild-type and mutant enzymes in yeast strains
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Han, B.W.; Lee, J.Y.; Yang, J.K.; Lee, B.I.; Suh, S.W.
Crystallization and preliminary X-ray crystallographic analysis of deoxyuridine triphosphate nucleotidohydrolase from Saccharomyces cerevisiae
Acta Crystallogr. Sect. D
57
1147-1149
2001
Saccharomyces cerevisiae
Galperin, M.Y.; Moroz, O.V.; Wilson, K.S.; Murzin, A.G.
House cleaning, a part of good housekeeping
Mol. Microbiol.
59
5-19
2006
Saccharomyces cerevisiae, Campylobacter jejuni, Escherichia coli, Leishmania major, Staphylococcus aureus, Trypanosoma cruzi, Mycobacterium tuberculosis (P9WNS5), Mycobacterium tuberculosis H37Rv (P9WNS5)
Guillet, M.; Van Der Kemp, P.A.; Boiteux, S.
dUTPase activity is critical to maintain genetic stability in Saccharomyces cerevisiae
Nucleic Acids Res.
34
2056-2066
2006
Saccharomyces cerevisiae (P33317), Saccharomyces cerevisiae
Tchigvintsev, A.; Singer, A.U.; Flick, R.; Petit, P.; Brown, G.; Evdokimova, E.; Savchenko, A.; Yakunin, A.F.
Structure and activity of the Saccharomyces cerevisiae dUTP pyrophosphatase DUT1, an essential housekeeping enzyme
Biochem. J.
437
243-253
2011
Saccharomyces cerevisiae (P33317), Saccharomyces cerevisiae
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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