Information on EC 3.6.1.55 - 8-oxo-dGTP diphosphatase

Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
Specify your search results
Mark a special word or phrase in this record:
Select one or more organisms in this record:
Show additional data
Do not include text mining results
Include (text mining) results (more...)
Include results (AMENDA + additional results, but less precise; more...)


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

EC NUMBER
COMMENTARY
3.6.1.55
-
RECOMMENDED NAME
GeneOntology No.
8-oxo-dGTP diphosphatase
-
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
8-oxo-dGTP + H2O = 8-oxo-dGMP + diphosphate
show the reaction diagram
-
-
-
-
PATHWAY
KEGG Link
MetaCyc Link
oxidized GTP and dGTP detoxification
-
SYSTEMATIC NAME
IUBMB Comments
8-oxo-dGTP diphosphohydrolase
This enzyme hydrolyses the phosphoanhydride bond between the alpha and beta phosphate of 8-oxoguanine-containing nucleoside di- and triphosphates thereby preventing misincorporation of the oxidized purine nucleoside triphosphates into DNA. It does not hydrolyse 2-hydroxy-dATP (cf. EC 3.6.1.56, 2-hydroxy-dATP diphosphatase) [4]. Requires Mg2+.
SYNONYMS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
7,8-dihydro-8-oxo-dGTP pyrophosphohydrolase
-
-
8-oxo-dGTP diphosphatase
-
-
CiMutT
-
CiMutT is a functional homologue of Escherichia coli MutT
MTH1
P36639
-
MutT
Q6G5F4
-
MutT
P08337
-
MutT
Escherichia coli strain CC101
-
-
-
MutT homologue 1
P36639
-
Nudix hydrolase
Q6G5F4
-
NUDT1
P36639
-
ORGANISM
COMMENTARY
LITERATURE
SEQUENCE CODE
SEQUENCE DB
SOURCE
Escherichia coli strain CC101
-
-
-
Manually annotated by BRENDA team
-
SwissProt
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
malfunction
-
the increase in the production of erroneous proteins by oxidative damage is 28fold over the wild-type cells in Escherichia coli mutT deficient cells
physiological function
-
the oxidized nucleotide precursors 8-oxo-dGTP is readily incorporated into nascent DNA strands during replication, which would cause base substitution mutations. 8-oxo-dGTP diphosphatase (8-oxo-dGTP diphosphatase) enzyme has the potential to prevent mutations by 8-oxo-dGTP in Ciona intestinalis
physiological function
-
MutT molecules are needed for keeping the spontaneous mutation frequency at the normal level. The MutT functions are not needed under anaerobic condition, yet the level of the MutT protein in cell is kept constant, probably for preparing for sudden changes of oxygen pressure
physiological function
-
the enzyme prevents replicational errors by degrading 8-oxo-dGTP, a potent mutagenic substrate for DNA synthesis. Elimination from the nucleotide pool of the oxidized form of guanine nucleotide is important for the high fidelity of DNA synthesis
physiological function
-
is produced in cells by reactive oxygen species normally formed during cellular metabolic processes. This oxidized base can pair with both adenine and cytosine, and thus the existence of this base in messenger RNA would cause translational errors. The MutT protein of Escherichia coli degrades 8-oxoGua-containing ribonucleoside di- and triphosphates to the monophosphate, thereby preventing the misincorporation of 8-oxoGua into RNA
physiological function
Escherichia coli strain CC101
-
MutT molecules are needed for keeping the spontaneous mutation frequency at the normal level. The MutT functions are not needed under anaerobic condition, yet the level of the MutT protein in cell is kept constant, probably for preparing for sudden changes of oxygen pressure
-
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
7,8-dihydro-8-oxo-GTP + H2O
7,8-dihydro-8-oxo-GMP + diphosphate
show the reaction diagram
Q6G5F4
-
-
-
?
8-oxo-dGDP + H2O
8-oxo-dGMP + phosphate
show the reaction diagram
-
-
-
-
?
8-oxo-dGTP + H2O
8-oxo-dGMP + diphosphate
show the reaction diagram
-
-
-
-
?
8-oxo-dGTP + H2O
8-oxo-dGMP + diphosphate
show the reaction diagram
-
-
-
-
?
8-oxo-dGTP + H2O
8-oxo-dGMP + diphosphate
show the reaction diagram
P36639
-
-
-
?
8-oxo-dGTP + H2O
8-oxo-dGMP + diphosphate
show the reaction diagram
-
8-oxo-dGTP i.e. 8-oxo-7,8-dihydro-2'-deoxyguanosine 5'-triphosphate
-
-
?
8-oxo-dGTP + H2O
8-oxo-dGMP + diphosphate
show the reaction diagram
-
8-oxoguanine (8-oxo-7,8-dihydroguanine) is produced in nucleic acids as well as in nucleotide pools of cells, by reactive oxygen species normally formed during cellular metabolic processes. MutT protein of Escherichia coli specifically degrades 8-oxoGua-containing deoxyribo- and ribonucleoside triphosphates to corresponding nucleoside monophosphates, thereby preventing misincorporation of 8-oxoguanine into DNA and RNA, which would cause mutation and phenotypic suppression, respectively
-
-
?
8-oxo-dGTP + H2O
8-oxo-dGMP + diphosphate
show the reaction diagram
-
MutT molecules are needed for keeping the spontaneous mutation frequency at the normal level. The MutT functions are not needed under anaerobic condition, yet the level of the MutT protein in cell is kept constant, probably for preparing for sudden changes of oxygen pressure
-
-
?
8-oxo-dGTP + H2O
8-oxo-dGMP + diphosphate
show the reaction diagram
-
prevents replicational errors by degrading 8-oxo-dGTP, a potent mutagenic substrate for DNA synthesis. Elimination from the nucleotide pool of the oxidized form of guanine nucleotide is important for the high fidelity of DNA synthesis
-
-
?
8-oxo-dGTP + H2O
8-oxo-dGMP + diphosphate
show the reaction diagram
P08337
the activity of MutT can prevent the misincorporation of 8-oxoguanine opposite adenine in DNA
-
-
?
8-oxo-dGTP + H2O
8-oxo-dGMP + diphosphate
show the reaction diagram
-
the MutT protein specifically hydrolyzes both 8-oxo-deoxyguanosine triphosphate (8-oxo-dGTP) and 8-oxo-guanosine triphosphate (8-oxo-GTP), which are otherwise incorporated in DNA and RNA opposite template A. This cleaning of the nucleotide pools decreases both DNA replication and transcription errors
-
-
?
8-oxo-dGTP + H2O
8-oxo-dGMP + diphosphate
show the reaction diagram
-
the oxidized nucleotide precursors 8-oxo-dGTP is readily incorporated into nascent DNA strands during replication, which would cause base substitution mutations. 8-oxo-dGTP diphosphatase (8-oxo-dGTP diphosphatase) enzyme has the potential to prevent mutations by 8-oxo-dGTP in Ciona intestinalis
-
-
?
8-oxo-dGTP + H2O
8-oxo-dGMP + diphosphate
show the reaction diagram
-
experimental thermodynamic data of 8-oxo-dGMP and dGMP binding to MutT show largely different affinities, even though the difference of chemical structures of the two molecules is very small. Enthalpic and entropic components of the binding free energy suggest drastically different conformational responses of MutT for binding the two molecules. These different conformational responses appear to be the mechanism for the enhanced recognition/discrimination between the two molecules despite a small difference of the chemical structures. Transition between two minimum energy substates, both existing in the native state of the protein, is involved in high-resolution molecular recognition
-
-
?
8-oxo-dGTP + H2O
8-oxo-dGMP + diphosphate
show the reaction diagram
P08337
MutT exhibits high substrate specificity for 8-oxoguanine nucleotides by the ligand-induced conformational change
-
-
?
8-oxo-dGTP + H2O
8-oxo-dGMP + diphosphate
show the reaction diagram
-
specfic for the MutT protein hydrolyses other dNTPs and GTP with lower Vmax and extremely high Km-values
-
-
?
8-oxo-dGTP + H2O
8-oxo-dGMP + diphosphate
show the reaction diagram
-
the MutT protein has an ability to cleave the phosphoanhydride bond between the alpha and beta phosphate of 8-oxoguanine-containing nucleoside di- and triphosphates. 8-oxo-dGTP is hydrolysed with the highest efficiency
-
-
?
8-oxo-dGTP + H2O
8-oxo-dGMP + diphosphate
show the reaction diagram
-
the specific activity for 8-oxo-dGTP is greater than that for unoxidized dATP and dGTP
-
-
?
8-oxo-dGTP + H2O
8-oxo-dGMP + diphosphate
show the reaction diagram
-
the unusually high affinity of MutT for 8-oxo-nucleotides is due not only to interactions with the altered 8-oxo or 7-NH positions on guanine, but results primarily from diffuse structural changes which tighten the protein structure around the 8-oxo-nucleotide
-
-
?
8-oxo-dGTP + H2O
8-oxo-dGMP + diphosphate
show the reaction diagram
Escherichia coli strain CC101
-
-, MutT molecules are needed for keeping the spontaneous mutation frequency at the normal level. The MutT functions are not needed under anaerobic condition, yet the level of the MutT protein in cell is kept constant, probably for preparing for sudden changes of oxygen pressure
-
-
?
8-oxo-GDP + H2O
8-oxo-GMP + phosphate
show the reaction diagram
-
-
-
-
?
8-oxo-GDP + H2O
8-oxo-GMP + phosphate
show the reaction diagram
P36639
-
-
-
?
8-oxo-GTP + H2O
8-oxo-GMP + diphosphate
show the reaction diagram
-
-
-
-
?
8-oxo-GTP + H2O
8-oxo-GMP + diphosphate
show the reaction diagram
-
the MutT protein eliminates 8-oxoGTP and prevents the occurrence of transcriptional errors, which are induced particularly in the aerobic state
-
-
?
dGDP + H2O
dGMP + phosphate
show the reaction diagram
-
-
-
-
?
dGTP + H2O
dGMP + diphosphate
show the reaction diagram
-
-
-
-
?
GDP + H2O
GMP + phosphate
show the reaction diagram
-
-
-
-
?
GTP + H2O
GMP + diphosphate
show the reaction diagram
-
-
-
-
?
additional information
?
-
-
in addition the enzyme hydrolyzes all four of the unoxidized nucleoside triphosphates, with a preference for dATP
-
-
-
additional information
?
-
-
no hydrolysis of 2-hydroxy-dATP
-
-
-
additional information
?
-
-
no hydrolysis of 2-hydroxy-dATP and 8-oxo-dATP, (R)-8,5'-cyclo-dATP, other forms of oxidized dATP, 5-oxo-dCTP and 5-formyl-dUTP are not hydrolyzed by the MutT enzyme
-
-
-
additional information
?
-
-
no hydrolysis of 2-hydroxy-dATP, 8-oxo-dGDP and 2-oxo-dAMP. The enzyme oxidizes all four unoxidized nucleoside triphosphates with a preference for dATP
-
-
-
additional information
?
-
P36639
the enzyme does not cleave 8-oxo-dGDP
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
8-oxo-dGDP + H2O
8-oxo-dGMP + phosphate
show the reaction diagram
-
-
-
-
?
8-oxo-dGTP + H2O
8-oxo-dGMP + diphosphate
show the reaction diagram
-
-
-
-
?
8-oxo-dGTP + H2O
8-oxo-dGMP + diphosphate
show the reaction diagram
-
-
-
-
?
8-oxo-dGTP + H2O
8-oxo-dGMP + diphosphate
show the reaction diagram
-
8-oxo-dGTP i.e. 8-oxo-7,8-dihydro-2'-deoxyguanosine 5'-triphosphate
-
-
?
8-oxo-dGTP + H2O
8-oxo-dGMP + diphosphate
show the reaction diagram
-
8-oxoguanine (8-oxo-7,8-dihydroguanine) is produced in nucleic acids as well as in nucleotide pools of cells, by reactive oxygen species normally formed during cellular metabolic processes. MutT protein of Escherichia coli specifically degrades 8-oxoGua-containing deoxyribo- and ribonucleoside triphosphates to corresponding nucleoside monophosphates, thereby preventing misincorporation of 8-oxoguanine into DNA and RNA, which would cause mutation and phenotypic suppression, respectively
-
-
?
8-oxo-dGTP + H2O
8-oxo-dGMP + diphosphate
show the reaction diagram
-
MutT molecules are needed for keeping the spontaneous mutation frequency at the normal level. The MutT functions are not needed under anaerobic condition, yet the level of the MutT protein in cell is kept constant, probably for preparing for sudden changes of oxygen pressure
-
-
?
8-oxo-dGTP + H2O
8-oxo-dGMP + diphosphate
show the reaction diagram
-
prevents replicational errors by degrading 8-oxo-dGTP, a potent mutagenic substrate for DNA synthesis. Elimination from the nucleotide pool of the oxidized form of guanine nucleotide is important for the high fidelity of DNA synthesis
-
-
?
8-oxo-dGTP + H2O
8-oxo-dGMP + diphosphate
show the reaction diagram
P08337
the activity of MutT can prevent the misincorporation of 8-oxoguanine opposite adenine in DNA
-
-
?
8-oxo-dGTP + H2O
8-oxo-dGMP + diphosphate
show the reaction diagram
-
the MutT protein specifically hydrolyzes both 8-oxo-deoxyguanosine triphosphate (8-oxo-dGTP) and 8-oxo-guanosine triphosphate (8-oxo-GTP), which are otherwise incorporated in DNA and RNA opposite template A. This cleaning of the nucleotide pools decreases both DNA replication and transcription errors
-
-
?
8-oxo-dGTP + H2O
8-oxo-dGMP + diphosphate
show the reaction diagram
-
the oxidized nucleotide precursors 8-oxo-dGTP is readily incorporated into nascent DNA strands during replication, which would cause base substitution mutations. 8-oxo-dGTP diphosphatase (8-oxo-dGTP diphosphatase) enzyme has the potential to prevent mutations by 8-oxo-dGTP in Ciona intestinalis
-
-
?
8-oxo-dGTP + H2O
8-oxo-dGMP + diphosphate
show the reaction diagram
Escherichia coli strain CC101
-
MutT molecules are needed for keeping the spontaneous mutation frequency at the normal level. The MutT functions are not needed under anaerobic condition, yet the level of the MutT protein in cell is kept constant, probably for preparing for sudden changes of oxygen pressure
-
-
?
8-oxo-GDP + H2O
8-oxo-GMP + phosphate
show the reaction diagram
-
-
-
-
?
8-oxo-GTP + H2O
8-oxo-GMP + diphosphate
show the reaction diagram
-
the MutT protein eliminates 8-oxoGTP and prevents the occurrence of transcriptional errors, which are induced particularly in the aerobic state
-
-
?
METALS and IONS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
Mg2+
-
activates
Mg2+
-
5 mM required for optimal activity; required, optimal activity at 5 mM
Mg2+
Q6G5F4
the enzyme binds catalytically essential Mg2+
Mn2+
-
activates
INHIBITORS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
8-oxo-dGMP
-
noncompetitive inhibitor of dGTP hydrolysis
dGMP
-
noncompetitive inhibitor of dGTP hydrolysis
diphosphate
-
linear uncompetitive inhibitor of dGTP hydrolysis
KM VALUE [mM]
KM VALUE [mM] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.000058
-
8-oxo-dGDP
-
pH 8.0, 30C
0.000081
-
8-oxo-dGTP
-
pH 8.0, 30C
0.0169
-
8-oxo-dGTP
-
pH 9.5, 30C
0.48
-
8-oxo-dGTP
-
pH and temperature not specified in the publication
0.000045
-
8-oxo-GDP
-
pH 8.0, 30C
0.0117
-
8-oxo-GDP
P36639
in Tris-HCl buffer (pH 8.0), at 37C
0.00026
-
8-oxo-GTP
-
pH 8.0, 30C
0.17
-
dGDP
-
pH 8.0, 30C
1.1
-
dGTP
-
pH 8.0, 30C
0.35
-
GDP
-
pH 8.0, 30C
1
-
GTP
-
pH 8.0, 30C
TURNOVER NUMBER [1/s]
TURNOVER NUMBER MAXIMUM[1/s]
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
2.55
-
8-oxo-dGTP
-
pH 9.5, 30C
kcat/KM VALUE [1/mMs-1]
kcat/KM VALUE [1/mMs-1] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
15
-
8-oxo-dGTP
-
pH 9.5, 30C
83713
150
-
8-oxo-dGTP
-
pH 9.5, 30C
83713
Ki VALUE [mM]
Ki VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.000049
-
8-oxo-dGMP
-
pH 7.5, 23C, Mg2+-activated, Ki(slope)
0.000173
-
8-oxo-dGMP
-
pH 7.5, 23C, Mn2+-activated, Ki(slope)
0.000593
-
8-oxo-dGMP
-
pH 7.5, 23C, Mn2+-activated, Ki(intercept)
0.00162
-
8-oxo-dGMP
-
pH 7.5, 23C, Mg2+-activated, Ki(intercept)
1.74
-
dGMP
-
pH 7.5, 23C, Mg2+-activated, Ki(slope)
3.96
-
dGMP
-
pH 7.5, 23C, Mn2+-activated, Ki(slope)
4.57
-
dGMP
-
pH 7.5, 23C, Mn2+-activated, Ki(intercept)
14.5
-
dGMP
-
pH 7.5, 23C, Mg2+-activated, Ki(intercept)
0.413
-
diphosphate
-
pH 7.5, 23C, Mn2+-activated, Ki(intercept)
4.95
-
diphosphate
-
pH 7.5, 23C, Mg2+-activated, Ki(intercept)
SPECIFIC ACTIVITY [µmol/min/mg]
SPECIFIC ACTIVITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
11.8
-
-
pH 9.5, 30C, 8-oxo-dGTP
pH OPTIMUM
pH MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
7.5
-
-
assay at
pH RANGE
pH RANGE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
8.5
10.5
-
pH 8.5: about 60% of maximal activity, pH 10.5: about 50% of maximal activity
TEMPERATURE OPTIMUM
TEMPERATURE OPTIMUM MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
23
-
-
assay at
30
-
-
assay at
30
-
-
assay at
37
-
-
assay at
TEMPERATURE RANGE
TEMPERATURE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
20
38
-
20C: about 50% of maximal activity, 38C: about 80% of maximal activity
MOLECULAR WEIGHT
MOLECULAR WEIGHT MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
20400
-
-
gel filtration
Crystallization/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
sitting drop vapor diffusion method, using 0.1 M HEPES, pH 7.5, 10% (w/v) PEG 4000, 0.1 M MgCl2
Q6G5F4
the crystal structures of MutT in the apo and holo forms and in the binary and ternary forms complexed with the product 8-oxo-dGMP and 8-oxo-dGMP plus Mn2+, respectively, are determined
P08337
TEMPERATURE STABILITY
TEMPERATURE STABILITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
60
-
Q6G5F4
the enzyme irreversibly unfolds and precipitates out of solution upon heating, with a melting temperature of 60C
Purification/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
nickel Sepharose column chromatography and Superdex 75 gel filtration
Q6G5F4
HisTrap column chromatography, HiTrap heparin column chromatography, and Mono S column chromatography
P36639
Cloned/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
expressed in Escherichia coli BL21(DE3)-R3-pRARE2 cells
Q6G5F4
expression in Escherichia coli CC101 mttT mutant; expression in Escherichia coli mutT mutant. CiMutT significantly suppressed the mutator activity of Escherichia coli mutT mutant
-
expression in Escherichia coli
P08337
MutT protein is produced as a His-tagged form in Escherichia coli M15
-
expressed in Escherichia coli BL21 cells
P36639
EXPRESSION
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
MutT molecules are needed for keeping the spontaneous mutation frequency at the normal level. The MutT functions are not needed under anaerobic condition, yet the level of the MutT protein in cell is kept constant, probably for preparing for sudden changes of oxygen pressure
-
MutT molecules are needed for keeping the spontaneous mutation frequency at the normal level. The MutT functions are not needed under anaerobic condition, yet the level of the MutT protein in cell is kept constant, probably for preparing for sudden changes of oxygen pressure
Escherichia coli strain CC101
-
-