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Information on EC 2.1.1.63 - methylated-DNA-[protein]-cysteine S-methyltransferase and Organism(s) Homo sapiens

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EC Tree
IUBMB Comments
This protein is involved in the repair of methylated DNA. Unlike EC 3.2.2.20, DNA-3-methyladenine glycosidase I and EC 3.2.2.21, DNA-3-methyladenine glycosidase II, which remove the methylated base leaving an apurinic/apyrimidinic site, this enzyme transfers the methyl group from the methylated DNA to an internal cysteine residue, leaving an intact nucleotide. Since the methyl transfer is irreversible, the enzyme can only catalyse a single turnover.
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Homo sapiens
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The taxonomic range for the selected organisms is: Homo sapiens
The enzyme appears in selected viruses and cellular organisms
Synonyms
o6-methylguanine-dna methyltransferase, atase, o6-alkylguanine-dna alkyltransferase, ada protein, o6-methylguanine dna methyltransferase, o6-methylguanine-dna-methyltransferase, o6-methylguanine methyltransferase, o6-alkylguanine dna alkyltransferase, o6-mgmt, methylguanine dna methyltransferase, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Ada protein
-
-
-
-
AGAT
-
-
C-hAGT
-
-
methylated-DNA-[protein]-cysteine S-methyltransferase
-
-
N-hAGT
-
-
O6-alkylguanine DNA alkyltransferase
-
-
O6-alkylguanine DNA-alkyltransferase
-
-
O6-alkylguanine-DNA alkyl-transferase
-
-
O6-alkylguanine-DNA alkyltransferase
O6-methylguanine DNA methyltransferase
O6-methylguanine-DNA methyltransferase
O6-methylguanine-DNA-methyltransferase
-
-
O6-MGMT
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
methyl group transfer
SYSTEMATIC NAME
IUBMB Comments
DNA-6-O-methylguanine/DNA-4-O-methylthymine:[protein]-L-cysteine S-methyltransferase
This protein is involved in the repair of methylated DNA. Unlike EC 3.2.2.20, DNA-3-methyladenine glycosidase I and EC 3.2.2.21, DNA-3-methyladenine glycosidase II, which remove the methylated base leaving an apurinic/apyrimidinic site, this enzyme transfers the methyl group from the methylated DNA to an internal cysteine residue, leaving an intact nucleotide. Since the methyl transfer is irreversible, the enzyme can only catalyse a single turnover.
CAS REGISTRY NUMBER
COMMENTARY hide
77271-19-3
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
DNA (containing 6-O-benzylguanine) + protein L-cysteine
DNA (without 6-O-benzylguanine) + protein S-benzyl-L-cysteine
show the reaction diagram
-
-
-
-
?
DNA (containing 6-O-carboxymethylguanine) + protein L-cysteine
DNA (without 6-O-carboxymethylguanine) + protein S-carboxymethyl-L-cysteine
show the reaction diagram
-
-
-
-
?
DNA (containing 6-O-methylguanine) + protein L-cysteine
DNA (without 6-O-methylguanine) + protein S-methyl-L-cysteine
show the reaction diagram
DNA (containing 6-O-methylguanine) + [protein] L-cysteine
DNA (without 6-O-methylguanine) + [protein] S-methyl-L-cysteine
show the reaction diagram
DNA (containing 6-O-methylguanine) + [protein]-L-cysteine
DNA (without 6-O-methylguanine) + [protein]-S-methyl-L-cysteine
show the reaction diagram
DNA (containing O6-chloroethylguanine) + protein L-cysteine
DNA (without O6-chloroethylguanine) + protein S-chloroethyl-L-cysteine
show the reaction diagram
-
-
-
-
?
DNA (containing O6-[4-oxo-4-(3-pyridyl)butyl]guanine) + protein L-cysteine
DNA (without O6-[4-oxo-4-(3-pyridyl)butyl]guanine) + protein S-4-oxo-4-(3-pyridyl)butyl-L-cysteine
show the reaction diagram
-
-
-
-
?
DNA containing 4-O-methylthymine + [protein-L-cysteine
DNA lacking 4-O-methylthymine + [protein]-S-methyl-L-cysteine
show the reaction diagram
DNA containing 6-O-benzylguanine + [protein]-L-cysteine
DNA lacking 6-O-benzylguanine + [protein]-S-methyl-L-cysteine
show the reaction diagram
-
AGT binds and scans DNA rapidly, flips O6-alkylG residues, transfers the alkyl group in a chemical step that is not rate-limiting in the case of 6-O-benzylguanine and releases the dealkylated DNA
-
-
?
DNA containing 6-O-ethylguanine + [protein]-L-cysteine
DNA lacking 6-O-ethylguanine +[protein]-S-ethyl-L-cysteine
show the reaction diagram
-
CGC(e6G)AGCTCGCG
-
?
DNA containing 6-O-methylguanine + [protein]-L-cysteine
DNA lacking 6-O-methylguanine + [protein]-S-methyl-L-cysteine
show the reaction diagram
DNA containing O6-(4-oxo-4-(3-pyridyl)butyl)guanine
?
show the reaction diagram
-
-
-
-
?
[N-[2-(2-[2-[(3-[[(2-amino-9H-purin-6-yl)oxy]methyl]phenyl)methoxy]ethoxy]ethoxy)ethyl]-5-(3,5-dimethyl-1H-pyrrol-2-yl-kappaN)-5-(3,5-dimethyl-2H-pyrrol-2-ylidene-kappaN)pentanamidato](difluoro)boron + [protein]-L-cysteine
[protein]-S-methyl-L-cysteine + ?
show the reaction diagram
-
-
-
-
?
additional information
?
-
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
DNA (containing 6-O-carboxymethylguanine) + protein L-cysteine
DNA (without 6-O-carboxymethylguanine) + protein S-carboxymethyl-L-cysteine
show the reaction diagram
-
-
-
-
?
DNA (containing 6-O-methylguanine) + protein L-cysteine
DNA (without 6-O-methylguanine) + protein S-methyl-L-cysteine
show the reaction diagram
DNA (containing 6-O-methylguanine) + [protein] L-cysteine
DNA (without 6-O-methylguanine) + [protein] S-methyl-L-cysteine
show the reaction diagram
-
the DNA repair protein O6-alkylguanine-DNA alkyltransferase is a principal mechanism of cellular resistance to the toxic and mutagenic effects of DNA damage produced by certain monofunctional alkylating agents. ATase operates by the transfer of the offending alkyl groups from the O6 position of guanine and the O4 position of thymine in damaged DNA to a cysteine residue at the active site of the protein. This is an irreversible process that results in the stoichiometric inactivation of the protein
-
-
ir
DNA (containing 6-O-methylguanine) + [protein]-L-cysteine
DNA (without 6-O-methylguanine) + [protein]-S-methyl-L-cysteine
show the reaction diagram
DNA (containing O6-chloroethylguanine) + protein L-cysteine
DNA (without O6-chloroethylguanine) + protein S-chloroethyl-L-cysteine
show the reaction diagram
-
-
-
-
?
DNA (containing O6-[4-oxo-4-(3-pyridyl)butyl]guanine) + protein L-cysteine
DNA (without O6-[4-oxo-4-(3-pyridyl)butyl]guanine) + protein S-4-oxo-4-(3-pyridyl)butyl-L-cysteine
show the reaction diagram
-
-
-
-
?
DNA containing 4-O-methylthymine + [protein-L-cysteine
DNA lacking 4-O-methylthymine + [protein]-S-methyl-L-cysteine
show the reaction diagram
-
DNA-repair enzyme
-
-
?
DNA containing 6-O-methylguanine + [protein]-L-cysteine
DNA lacking 6-O-methylguanine + [protein]-S-methyl-L-cysteine
show the reaction diagram
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Zinc
-
in bacterial expression systems, recombinant hAGT is produced in increasingly larger quantities when growth media are supplemented with up to 0.1 mM ZnCl2. Metal-enriched hAGT samples have a 5fold increase in repair rate constant over conventionally purified protein samples and a 60fold increase over metal-stripped hAGT. Zinc confers a mechanistic enhancement to repair activity that does not result from an increase in substrate binding affinity. Zinc also provides conformational stability to hAGT that may influence its regulation
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
2-([2-amino-6-[(4-bromothiophen-2-yl)methoxy]-9H-purin-9-yl]methoxy)ethanol
-
-
2-amino-O4-benzyl-6,7-dimethylpteridine
-
potent
2-amino-O4-benzyl-6-formylpteridine
-
potent
2-amino-O4-benzyl-6-hydroxymethylpteridine
-
potent
2-amino-O4-benzylpteridine
-
potent
2-amino-O4-benzylpteridine-6-carboxylic acid
-
potent
2-hexaprenyl-6-methoxy-1,4-benzoquinone
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-
4-[(4-bromothiophen-2-yl)methoxy]-1H-pyrazolo[3,4-d]pyrimidin-6-amine
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-
4-[bis(2-chloroethyl)amino]-L-phenylalanine
-
hyperthermia enhances the inhibitory effects of L-phenylalanine mustard on melanoma cell growth
6-(1-benzofuran-2-ylmethoxy)-9H-purin-2-amine
-
-
6-(4,5,6,7-tetrahydro-1-benzothiophen-2-ylmethoxy)-9H-purin-2-amine
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6-(naphtho[1,2-b]thiophen-2-ylmethoxy)-9H-purin-2-amine
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-
6-(naphtho[2,1-b]thiophen-2-ylmethoxy)-9H-purin-2-amine
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6-(phenanthro[9,10-b]thiophen-2-ylmethoxy)-9H-purin-2-amine
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-
6-[(1-methyl-4-nitro-1H-pyrrol-2-yl)methoxy]-9H-purin-2-amine
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6-[(4-bromothiophen-2-yl)methoxy]-9-(2-deoxy-beta-D-erythro-pentofuranosyl)-9H-purin-2-amine
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-
7-[(4-bromothiophen-2-yl)methoxy]-2,3-dihydro-1H-[1,2,3]triazolo[4,5-d]pyrimidin-5-amine
-
-
9-beta-D-arabinofuranosyl-6-[(4-bromothiophen-2-yl)methoxy]-9H-purin-2-amine
-
-
alkyltransferase-like protein
inhibits the transfer of methyl groups to MGMT, thus the action of MGMT on 6-O-methylguanine in DNA, inhibition is reversible by prolonged incubation in the presence of MGMT
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Br(CH2)2Br
-
inactivates purified AGT and mutant R128A to approximately the same extent; inactivates purified AGT and mutant R128A to approximately the same extent, small reduction in the loss of activity in the absence of DNA, but no effect at all in the presence of DNA, inactivates mutant Y114A much less than wild-type, and DNA completely prevents this inactivation, mutants P140K and Y158H are less inactivated than wild-type AGT, specifically in the presence of DNA
Br(CH2)3Br
-
mutant P140K requires higher concentrations than wild-type AGT for inactivation
Br(CH2)5Br
-
mutant P140K requires higher concentrations than wild-type AGT for inactivation
BrCH2Br
-
wild-type AGT and mutant P140K show no difference in sensitivity to BrCH2Br
BrCH2OAc
-
reacts with the enzyme at its cysteine acceptor site, abolishing its DNA repair activity, the formation of AGT-Cys145S-CH2Br by BrCH2OAc
CH2Br2
-
reacts with the enzyme at its cysteine acceptor site, abolishing its DNA repair activity
DNA (containing 6-O-carboxymethylguanine)
-
-
-
DNA (containing 6-O-methylguanine)
-
-
double-stranded oligonucleotides
-
6-O-methylguanine, 6-O-(4-fluorobenzyl)-guanine, 6-O-(3-fluorobenzyl)-guanine, 6-O-(2-fluorobenzyl)-guanine, 6-O-benzylguanine, 6-O-benzylhypoxanthine. IC50: 1.4-3.0 nM
-
formaldehyde
-
decreases activity at levels up to 3fold higher than the maximally allowed workplace concentration, no decrease at the maximally allowed level
methotrexate
-
-
methyl iodide
-
can directly alkylate the active site of the enzyme, the agent can increase the effectiveness of environmental and endogenously produced alkylating carcinogens in producing the mutagenic 6-O-alkylguanine residue in DNA in vivo
methyl isocyanate
-
methyl isocyanate resulting from base-catalyzed activation of VNP40101M inhibits the enzyme, thereby enhancing the yield of the DNA G-C interstrand crosslink responsible for the antitumor activity of this agent
N9-cyclopentyl-O6-(4-bromothenyl)guanine
efficient inhibitor of wild-type AGT
Na2SO4
-
-
Na3 citrate
-
-
NaCl
-
0.2 M, 80% inhibition
Ni2+
-
purified protein is not very sensitive to this metal but the loss of AGT could contribute to the well-known carcinogenicity of nickel
O4-(4-bromothenylpterin)
-
-
O4-benzylfolic acid
-
30times more active than O6-benzylguanine against the wild-type alkyltransferase, inactivation of P140K mutant alkyltransferase. Inhibitor shows promise as an agent for possible tumor-selective alkyltransferase inactivation superior toO6-benzylguanine as a chemotherapy adjuvant
O6-(1,2-thiazol-4-ylmethyl)guanine
-
-
O6-(1,3-oxazol-5-yl)guanine
-
-
O6-(1,3-thiazol-5-yl)guanine
-
-
O6-(1-benzofuran-2-ylmethyl)guanine
-
-
O6-(2-benzo[b]thienylmethyl)guanine
-
-
O6-(3-pyridyl)guanine
-
-
O6-(4-(2-chloropyridyl))guanine
-
-
O6-(4-bromothenyl)-8-oxaguanine
-
-
O6-(4-bromothenyl)-8-thiaguanine
-
-
O6-(4-bromothenyl)guanine
O6-(4-pyridyl)guanine
-
-
O6-alkylating drugs
-
O6-alkylating drugs deplete MGMT activity indirectly via alkylation of DNA
-
O6-benzyl guanine
-
-
O6-benzyl-2'-deoxyguanosine
-
-
O6-benzylguanine
O6-furfurylguanine
-
-
O6-methylguanine
-
-
O6-methylguanine oligonucleotide
-
preincubation of extracts with a short oligonucleotide containing a single O6-methylguanine residue causes essentially complete loss of ATase activity
-
O6-thenylguanine
-
original Patrin, became Patrin-1
O6-[(1-methyl-1H-imidazol-5-yl)methyl]guanine
-
-
temozolomide
VNP40101M
-
methyl isocyanate resulting from base-catalyzed activation of VNP40101M inhibits the enzyme, thereby enhancing the yield of the DNA G-C interstrand crosslink responsible for the antitumor activity of this agent
additional information
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1,2,3,4-diepoxybutane
-
induces AGT-DNA cross-linking, takes place exclusively at the cysteine residues within the protein
activator of protein kinase C
-
increases the level of AGT mRNA and increases resistance to N,N'-bis(2-chloroethyl)-N-nitrosourea in HeLa cells
-
dexamethasone
-
-
glucocorticoid
-
inhibitor of protein phosphatase
-
increases the level of AGT mRNA and increases resistance to N,N'-bis(2-chloroethyl)-N-nitrosourea in HeLa cells
-
additional information
-
DNA damage, ionizing radiation
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
additional information
additional information
-
-
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
additional information
additional information
-
second order repair rate constants of 6-O-methyl and 6-O-ethylguanine containing substrates
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.00033
2-([2-amino-6-[(4-bromothiophen-2-yl)methoxy]-9H-purin-9-yl]methoxy)ethanol
Homo sapiens
-
-
0.000006
4-[(4-bromothiophen-2-yl)methoxy]-1H-pyrazolo[3,4-d]pyrimidin-6-amine
Homo sapiens
-
-
0.00008
6-(1-benzofuran-2-ylmethoxy)-9H-purin-2-amine
Homo sapiens
-
-
0.185
6-(4,5,6,7-tetrahydro-1-benzothiophen-2-ylmethoxy)-9H-purin-2-amine
Homo sapiens
-
-
0.000022
6-(naphtho[1,2-b]thiophen-2-ylmethoxy)-9H-purin-2-amine
Homo sapiens
-
-
0.00005
6-(naphtho[2,1-b]thiophen-2-ylmethoxy)-9H-purin-2-amine
Homo sapiens
-
-
0.0011
6-(phenanthro[9,10-b]thiophen-2-ylmethoxy)-9H-purin-2-amine
Homo sapiens
-
-
0.00055
6-[(1-methyl-4-nitro-1H-pyrrol-2-yl)methoxy]-9H-purin-2-amine
Homo sapiens
-
-
0.000095
6-[(4-bromothiophen-2-yl)methoxy]-9-(2-deoxy-beta-D-erythro-pentofuranosyl)-9H-purin-2-amine
Homo sapiens
-
-
0.000045
7-[(4-bromothiophen-2-yl)methoxy]-2,3-dihydro-1H-[1,2,3]triazolo[4,5-d]pyrimidin-5-amine
Homo sapiens
-
-
0.000115
9-beta-D-arabinofuranosyl-6-[(4-bromothiophen-2-yl)methoxy]-9H-purin-2-amine
Homo sapiens
-
-
0.0000018
DNA (containing 6-O-carboxymethylguanine)
Homo sapiens
-
in 50 mM Tris-HCl pH 8.3, at 37°C
-
0.00000093
DNA (containing 6-O-methylguanine)
Homo sapiens
-
in 50 mM Tris-HCl pH 8.3, at 37°C
0.0000014 - 0.000003
double-stranded oligonucleotides
Homo sapiens
-
6-O-methylguanine, 6-O-(4-fluorobenzyl)-guanine, 6-O-(3-fluorobenzyl)-guanine, 6-O-(2-fluorobenzyl)-guanine, 6-O-benzylguanine, 6-O-benzylhypoxanthine. IC50: 1.4-3.0 nM
-
0.0005
N9-cyclopentyl-O6-(4-bromothenyl)guanine
Homo sapiens
-
0.000025
O4-(4-bromothenylpterin)
Homo sapiens
-
-
0.00007
O6-(1,2-thiazol-4-ylmethyl)guanine
Homo sapiens
-
-
0.00035
O6-(1,3-oxazol-5-yl)guanine
Homo sapiens
-
-
0.000033
O6-(1,3-thiazol-5-yl)guanine
Homo sapiens
-
-
0.000035
O6-(1-benzofuran-2-ylmethyl)guanine
Homo sapiens
-
-
0.00003
O6-(2-benzo[b]thienylmethyl)guanine
Homo sapiens
-
-
0.00043
O6-(3-pyridyl)guanine
Homo sapiens
-
-
0.00004
O6-(4-(2-chloropyridyl))guanine
Homo sapiens
-
-
0.00024
O6-(4-bromothenyl)-8-oxaguanine
Homo sapiens
-
-
0.0000028
O6-(4-bromothenyl)-8-thiaguanine
Homo sapiens
-
-
0.0000001 - 0.0000034
O6-(4-bromothenyl)guanine
0.00013
O6-(4-pyridyl)guanine
Homo sapiens
-
-
0.00009 - 1.2
O6-benzylguanine
0.0003
O6-furfurylguanine
Homo sapiens
-
-
0.000018
O6-thenylguanine
Homo sapiens
-
-
0.0085
O6-[(1-methyl-1H-imidazol-5-yl)methyl]guanine
Homo sapiens
-
-
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
41.5
-
hyperthermic condition
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
AGT expression is increased in breast cancer compared to normal breast
Manually annotated by BRENDA team
-
activity is significantly decreased in samples from current smokers compared to nonsmokers
Manually annotated by BRENDA team
-
esophageal squamous cell carcinoma
Manually annotated by BRENDA team
-
low 6-O-methylguanine-DNA methyltransferase activity may contribute to the chemosensitivity of some human oligodendrogliomas
Manually annotated by BRENDA team
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
-
enzyme deficiency leads to a tremendously enhanced sensitivity toward alkylation-induced colorectal carcinogenesis
physiological function
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
MGMT_HUMAN
207
0
21646
Swiss-Prot
other Location (Reliability: 1)
A0A059PXT9_HUMAN
113
0
12474
TrEMBL
other Location (Reliability: 1)
A0A0G2SKE6_HUMAN
59
0
5834
TrEMBL
other Location (Reliability: 3)
A0A0G2SKF3_HUMAN
59
0
5860
TrEMBL
other Location (Reliability: 3)
B4DEE8_HUMAN
238
0
25050
TrEMBL
Mitochondrion (Reliability: 3)
E5BBQ0_HUMAN
182
0
19414
TrEMBL
other Location (Reliability: 1)
A0A059PXU1_HUMAN
49
0
5347
TrEMBL
other Location (Reliability: 2)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
19000
-
gel filtration, glycerol density gradient sedimentation
20900
-
x * 20900, SDS-PAGE
21000
-
x * 21000, SDS-PAGE
21614
x * 21860, SDS-PAGE, x * 21614, sequence analysis
21860
x * 21860, SDS-PAGE, x * 21614, sequence analysis
23000
-
-
24000
-
x * 24000, SDS-PAGE
25000
-
1 * 25000, SDS-PAGE
51000
-
enhanced green fluorescent protein-tagged enzyme, SDS-PAGE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
monomer
-
1 * 25000, SDS-PAGE
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
A121E
no major structural change upon energy minimization, is within the DNA binding region and may therefore affect DNA binding of MGMT
A121T
no major structural change upon energy minimization, is within the DNA binding region and may therefore affect DNA binding of MGMT
A154T
-
ca. 4fold increased activity, AGT mutant selected using phage display
A41D/S115T/I151N
-
1.6fold increased activity, AGT mutant selected using yeast three-hybrid system
C145A
C145F
-
appears to cause a similar change in the AGT structure as alkylation of the active site and provides a model for detailed study of the mechanism of degradation
C145S
-
inactive mutant enzyme forms a specific and stable complex with a 6-O-methylguanine-containing oligonucleotide substrate
C24A
-
mutation of Cys24 prevents the zinc-dependent alkyl transferase by N-terminal domain human AGT
D42E/A51T/A64V/K104M
-
0.5fold increased activity, AGT mutant selected using yeast three-hybrid system
D42E/P47L/V155L/K178M
-
1.9fold increased activity, AGT mutant selected using yeast three-hybrid system
E110D/L120M
-
0.7fold increased activity, AGT mutant selected using yeast three-hybrid system
E166D
no major structural change upon energy minimization
E25K
-
0.7fold increased activity, AGT mutant selected using yeast three-hybrid system
E92D/I151V/R175W
-
1.0fold increased activity, AGT mutant selected using yeast three-hybrid system
F79I/V88I/F89L
-
0.7fold increased activity, AGT mutant selected using yeast three-hybrid system
G122C
-
0.9fold increased activity, AGT mutant selected using yeast three-hybrid system
G132R
no major structural change upon energy minimization, is within the DNA binding region and may therefore affect DNA binding of MGMT
G156A
G156C
-
mutant form expressed by the medulloblastoma cell line D283 MED, mutant enzyme is not easily inhibited by O6-benzylguanine
G160R
G160W
-
cells overexpressing W160AGT do not become labeled, even when incubated with O6-propargylguanine for extended periods of time
H29A
-
does not show the stability enehancement of wild-type hAGT with its intact zinc coordination sphere
H71Y/A154T
-
3.3fold increased activity, AGT mutant selected using phage display
H85A
-
does not show the stability enehancement of wild-type hAGT with its intact zinc coordination sphere
I143V
I143V/K178R
K104E/T127A/A154T
-
4.5fold increased activity, AGT mutant selected using phage display
K107L
-
mutant is deficient in DNA repair
K107R/A154T
-
4.7fold increased activity, AGT mutant selected using phage display
K165R
-
does not abolish activity on 6-O-methylguanine but greatly reduces the ability to react with O6-benzylguanine
K165T
-
mutant form expressed by the medulloblastoma cell line D341 MED, mutant enzyme is not easily inhibited by O6-benzylguanine
K8R/K104E/I151T
-
1.4fold increased activity, AGT mutant selected using phage display
K8T/A51T/I112V/A154T
-
5.5fold increased activity, AGT mutant selected using phage display
K8T/T127A/A154T/H174R
-
5.8fold increased activity, AGT mutant selected using phage display
L33F/A68T
-
2.1fold increased activity, AGT mutant selected using yeast three-hybrid system
L33F/N123Y
-
2.2fold increased activity, AGT mutant selected using yeast three-hybrid system
L33F/V44A/V52A/A154T
-
6.1fold increased activity, AGT mutant selected using phage display
L66M/K131R
-
1.5fold increased activity, AGT mutant selected using yeast three-hybrid system
L84F/I143V/K178R
-
enhanced green fluorescent protein-tagged MGMT variants exhibit nuclear localization patterns indistinguishable from wild type enzyme, upon exposure to O6-benzylguanine, the L84F/I143V/K178R variant is degraded more rapidly than wild type
M1V/V164M
-
1.9fold increased activity, AGT mutant selected using phage display
N123S
-
1.3fold increased activity, AGT mutant selected using phage display
N123V
no major structural change upon energy minimization, is within the DNA binding region and may therefore affect DNA binding of MGMT
N150D
-
1.8fold increased activity, AGT mutant selected using phage display
N157/S159/C62A/C150N/G131K/G132T/M134L/R135S/Q115S/Q116H/K125A/A127T/R128A/S151I/S152N
-
called MAGT with 15 different mutations in a single protein, has23fold increase in activity relative to wild-type, is resistant against N9-substituted BG derivatives used for inhibition of wild-type, shows suppressed affinity towards DNA
P140A
-
70% reduced ability of the protein to react with Br(CH2)2Br
P140K
Q90R/K101N/F108I/V164L
-
1.2fold increased activity, AGT mutant selected using yeast three-hybrid system
R128A
R128G
R128K
active site mutant
R128L
-
reduces the AGT repair efficiency, smaller effects with the O6-benzylguanine substrate than the 6-O-methylguanine
R175L
-
0.6fold increased activity, AGT mutant selected using yeast three-hybrid system
T11I/N67K/Q72L
-
1.0fold increased activity, AGT mutant selected using yeast three-hybrid system
T127A
-
2.2fold increased activity, AGT mutant selected using phage display
T38M/A41D/A64T/G173C
-
0.8fold increased activity, AGT mutant selected using yeast three-hybrid system
V149I/A154T
-
4.5fold increased activity, AGT mutant selected using phage display
V44G/V106A/I151T/A170T
-
1.4fold increased activity, AGT mutant selected using yeast three-hybrid system
V46A/A50V/P58V/A154T
-
3.4fold increased activity, AGT mutant selected using phage display
V52A/I151S/K178E
-
2.3fold increased activity, AGT mutant selected using phage display
V52I/V164M
-
2.1fold increased activity, AGT mutant selected using yeast three-hybrid system
W65C
no major structural change upon energy minimization, possibly unstable
Y114A
Y114E
Y114F
Y158H
additional information
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
50
-
20 min, 55-65% loss of activity in absence of DNA, 25-35% loss of activity in presence of DNA, 0.2 mg/ml
65
-
the enzyme is inactivated after 5 min at 65°C
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
zinc provides conformational stability to hAGT that may influence its regulation
-
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
by immobilized metal affinity chromatography
-
DEAE-Sepharose column chromatography
-
immobilized metal affinity column chromatography
mutants purified by either nickel or glutathione affinity chromatography
-
recombinant enzyme
-
to apparent homogeneity
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
cDNA is cloned into a pET-11a plasmid and expressed in Escherichia coli
-
expressed in CHO-9 cells
-
expressed in Escherichia coli
-
expressed in Escherichia coli XL-1 Blue cells
expressed in Escherichia coliKT233 and in HeLa cells
-
expressed in HEK-293T cells as enhanced green fluorescent protein-tagged enzyme
-
expressed in U-87MG cells
-
expression in CHO cells
-
expression in Escherichia coli strain AB1157 and isogenic strain GWR111
expression in Escherichia coli TRG8
-
expression in Escherichia coli, transgenic overexpression in mouse skin, expression in CHO cells
-
expression of N-hAGT and C-hAGT in Escherichia coli XL1-Blue cells. N-hAGT, C-hAGT and full length AGT expressed from the pQE-30 vector in Escherichia coli GWR-109
-
ligated into the pHybLex/Zeo plasmid and electroporated into Escherichia coli XL1-Blue, yielding a library of at least 320000 independent clones, genes of selected AGT mutants subcloned into the pGEX-2T plasmid, allowing for the expression of the AGT mutants as GST fusion proteins
-
mutants subcloned into pGEX-2T for expression as a GST–AGT fusion, or into pET15b for expression as a 6 x His–AGT fusion protein
overexpressed in Escherichia coli strain UC978
-
overexpression in CHO-derived Tet-on-inducible cells, knockdown of MGMT expression with small interfering RNA in HONE-1 cells
-
recombinant AGT and mutants expressed in Escherichia coli, pQE expression vectors for wild-type and mutant AGT production and plasmid pREP4 cotransformed into TRG8 cells to suppress basal AGT protein expression
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
a loss of MGMT expression is noted in 20 cases of 60 total soft tissue sarcomas
-
ependymomas lack MGMT promoter hypermethylation and show high MGMT protein expression
-
extensive methylation of MGMT promoter is associated with loss/reduced protein expression, methylation of MGMT promoter region is essential for methylation-induced silencing of this gene
-
interleukin-24 down-regulates O6-methylguanine-DNA methyltransferase in melanoma cells, accumulation of functional p53 is essential for interleukin-24-induced down-regulation of O6-methylguanine-DNA methyltransferase
-
MGMT activity is significantly higher in the group with the lowest consumption of vegetables than in the group with the greatest vegetable consumption
-
microRNA-603 directly interacts with the 3'-UTR region of enzyme gene and produces a 6fold decrease of both enzyme mRNA and protein upon transfection in glioblastoma cell line in vitro. Downregulation of enzyme expression by microRNA-181d and microRNA-767-3p is due to degradation of the enzyme mRNA. microRNA-221 and microRNA-222 also downregulate the enzyme expression
-
neither short-term (24 h) nor long-term changes (7 weeks) in S-adenosyl-L-methionine/S-adenosylhomocysteine ratio alter global or MGMT promoter methylation, however, experimentally elevated S-adenosylhomocysteine levels significantly decrease MGMT mRNA levels by more than 50%
-
promoter methylation of O6-methylguanine-DNA-methyltransferase in lung cancer is regulated by p53
-
resistance to alkylating agents such as temozolomide correlates with increased expression of O6-methylguanine-DNA methyltransferase
-
there is a good correlation between the increasing MGMT promoter methylation and decreased MGMT expression, in most patients who has been treated with temozolomide, there is decreased MGMT expression in the post treatment sample when compared to the primary sample
-
treatment with 0.05 mM disulfiram reduces enzyme protein expression
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
analysis
diagnostics
-
introduction of the MS-MLPA assay may not only be helpful for predicting response of gliomas to temozolomide, but may also facilitate tailor-made treatment with other chemotherapeutic agents for a variety of tumors
drug development
-
highly effective inactivation of MGMT by an oligodeoxyribonucleotide containing O6-(4-bromothenyl)guanine suggests that such oligodeoxyribonucleotides might have therapeutic applications if problems of delivery can be addressed
medicine
molecular biology
modest binding cooperativity and high binding densities of AGT are adaptations that allow the enzyme to efficiently search for lesions in the context of chromatin remodeling and DNA replication
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Oh, H.K.; Teo, A.K.C.; Ali, R.B.; Lim, A.; Ayi, T.C.; Yarosh, D.B.; Li, B.F.L.
Conformational change in human DNA repair enzyme O6-methylguanine-DNA methyltransferase upon alkylation of its active site by SN1 (indirect-acting) and SN2 (direct-acting) alkylating agents: breaking a "salt-link"?
Biochemistry
35
12259-12266
1996
Homo sapiens
Manually annotated by BRENDA team
Hazra, T.K.; Roy, R.; Biswas, T.; Grabowski, D.T.; Pegg, A.E.; Mitra, S.
Specific recognition of O6-methylguanine in DNA by active site mutants of human O6-methylguanine-DNA methyltransferase
Biochemistry
36
5769-5776
1997
Homo sapiens
Manually annotated by BRENDA team
Terashima, I.; Kawate, H.; Sakumi, K.; Sekiguchi, M.; Kohda, K.
Substrate specificity of human O6-methylguanine-DNA methyltransferase for O6-benzylguanine derivatives in oligodeoxynucleotides
Chem. Res. Toxicol.
10
1234-1239
1997
Homo sapiens
Manually annotated by BRENDA team
Inoue, R.; Abe, M.; Nakabeppu, Y.; Sekiguchi, M.; Mori, T.; Suzuki, T.
Characterization of human polymorphic DNA repair methyltransferase
Pharmacogenetics
10
59-66
2000
Homo sapiens
Manually annotated by BRENDA team
Liem, L.K.; Lim, A.; Li, B.F.L.
Specificities of human, rat and E.coli O6-methylguanine-DNA methyltransferases towards the repair of O6-methyl and O6-ethylguanine in DNA
Nucleic Acids Res.
22
1613-1619
1994
Escherichia coli, Homo sapiens, Rattus norvegicus
Manually annotated by BRENDA team
Nutt, C.L.; Costello, J.F.; Bambrick, L.L.; Yarosh, D.B.; Swinnen, L.J.; Chambers, A.F.; Cairncross, J.G.
O6-Methylguanine-DNA methyltransferase in tumors and cells of the oligodendrocyte lineage
Can. J. Neurol. Sci.
22
111-115
1995
Homo sapiens, Rattus norvegicus
Manually annotated by BRENDA team
Chan, C.L.; Wu, Z.; Ciardelli, T.; Eastman, A.; Bresnick, E.
Kinetic and DNA-binding properties of recombinant human O6-methylguanine-DNA methyltransferase
Arch. Biochem. Biophys.
300
193-200
1993
Homo sapiens
Manually annotated by BRENDA team
Roy, R.; Shiota, S.; Kennel, S.J.; Raha, R.; von Wronski, M.; Brent, T.P.; Mitra, S.
A comparative study of the biochemical properties of human and mouse recombinant O6-methylguanine-DNA methyltransferases
Carcinogenesis
16
405-411
1995
Homo sapiens, Mus musculus
Manually annotated by BRENDA team
Mattern, J.; Eichhorn, U.; Kaina, B.; Volm, M.
O6-Methylguanine-DNA methyltransferase activity and sensitivity to cyclophosphamide and cisplatin in human lung tumor xenografts
Int. J. Cancer
77
919-922
1998
Homo sapiens
Manually annotated by BRENDA team
D'Atri, S.; Graziani, G.; Lacal, P.M.; Nistico, V.; Gilberti, S.; Faraoni, I.; Watson, A.J.; Bonmassar, E.; Margison, G.P.
Attenuation of O(6)-methylguanine-DNA methyltransferase activity and mRNA levels by cisplatin and temozolomide in jurkat cells
J. Pharmacol. Exp. Ther.
294
664-671
2000
Homo sapiens
Manually annotated by BRENDA team
Kreklau, E.L.; Liu, N.; Li, Z.; Cornetta, K.; Erickson, L.C.
Comparison of single- versus double-bolus treatments of O6-benzylguanine for depletion of O6-methylguanine DNA methyltransferase (MGMT) activity in vivo: development of a novel fluorometric oligonucleotide assay for measurement of MGMT activity
J. Pharmacol. Exp. Ther.
297
524-530
2001
Homo sapiens
Manually annotated by BRENDA team
Koike, G.; Maki, H.; Takeya, H.; Hayakawa, H.; Sekiguchi, M.
Purification, structure, and biochemical properties of human O6-methylguanine-DNA methyltransferase
J. Biol. Chem.
265
14754-14762
1990
Homo sapiens
Manually annotated by BRENDA team
Morgan, S.E.; Kelley, M.R.; Pieper, R.O.
The role of the carboxyl-terminal tail in human O6-methylguanine DNA methyltransferase substrate specificity and temperature sensitivity
J. Biol. Chem.
268
19802-19809
1993
Homo sapiens
Manually annotated by BRENDA team
Guengerich, F.P.; Fang, Q.; Liu, L.; Hachey, D.L.; Pegg, A.E.
O6-Alkylguanine-DNA alkyltransferase: low pKa and high reactivity of cysteine 145
Biochemistry
42
10965-10970
2003
Homo sapiens
Manually annotated by BRENDA team
Rasimas, J.J.; Kanugula, S.; Dalessio, P.M.; Ropson, I.J.; Fried, M.G.; Pegg, A.E.
Effects of zinc occupancy on human O6-alkylguanine-DNA alkyltransferase
Biochemistry
42
980-990
2003
Homo sapiens
Manually annotated by BRENDA team
Baumann, R.P.; Shyam, K.; Penketh, P.G.; Remack, J.S.; Brent, T.P.; Sartorelli, A.C.
1,2-Bis(methylsulfonyl)-1-(2-chloroethyl)-2-[(methylamino)carbonyl]hydrazine (VNP40101M): II. Role of O6-alkylguanine-DNA alkyltransferase in cytotoxicity
Cancer Chemother. Pharmacol.
53
288-295
2004
Homo sapiens
Manually annotated by BRENDA team
Liu, L.; Williams, K.M.; Guengerich, F.P.; Pegg, A.E.
O6-Alkylguanine-DNA alkyltransferase has opposing effects in modulating the genotoxicity of dibromomethane and bromomethyl acetate
Chem. Res. Toxicol.
17
742-752
2004
Homo sapiens
Manually annotated by BRENDA team
Fang, M.Z.; Jin, Z.; Wang, Y.; Liao, J.; Yang, G.Y.; Wang, L.D.; Yang, C.S.
Promoter hypermethylation and inactivation of O6-methylguanine-DNA methyltransferase in esophageal squamous cell carcinomas and its reactivation in cell lines
Int. J. Oncol.
26
615-622
2005
Homo sapiens
Manually annotated by BRENDA team
Rasimas, J.J.; Pegg, A.E.; Fried, M.G.
DNA-binding mechanism of O6-alkylguanine-DNA alkyltransferase
J. Biol. Chem.
278
7973-7980
2003
Homo sapiens
Manually annotated by BRENDA team
Nelson, M.E.; Loktionova, N.A.; Pegg, A.E.; Moschel, R.C.
2-Amino-O4-benzylpteridine derivatives: potent inactivators of O6-alkylguanine-DNA alkyltransferase
J. Med. Chem.
47
3887-3891
2004
Homo sapiens
Manually annotated by BRENDA team
Bacolod, M.D.; Johnson, S.P.; Pegg, A.E.; Dolan, M.E.; Moschel, R.C.; Bullock, N.S.; Fang, Q.; Colvin, O.M.; Modrich, P.; Bigner, D.D.; Friedman, H.S.
Brain tumor cell lines resistant to O6-benzylguanine/1,3-bis(2-chloroethyl)-1-nitrosourea chemotherapy have O6-alkylguanine-DNA alkyltransferase mutations
Mol. Cancer Ther.
3
1127-1135
2004
Homo sapiens
Manually annotated by BRENDA team
Esteller, M.; Herman, J.G.
Generating mutations but providing chemosensitivity: the role of O6-methylguanine DNA methyltransferase in human cancer
Oncogene
23
1-8
2004
Homo sapiens
Manually annotated by BRENDA team
Heinis, C.; Schmitt, S.; Kindermann, M.; Godin, G.; Johnsson, K.
Evolving the substrate specificity of O6-alkylguanine-DNA alkyltransferase through loop insertion for applications in molecular imaging
ACS Chem. Biol.
1
575-584
2006
Homo sapiens
Manually annotated by BRENDA team
Fang, Q.; Kanugula, S.; Pegg, A.E.
Function of domains of human O6-alkylguanine-DNA alkyltransferase
Biochemistry
44
15396-15405
2005
Homo sapiens
Manually annotated by BRENDA team
Geoerger, B.; Vassal, G.; Doz, F.; OQuigley, J.; Wartelle, M.; Watson, A.J.; Raquin, M.A.; Frappaz, D.; Chastagner, P.; Gentet, J.C.; Rubie, H.; Couanet, D.; Geoffray, A.; Djafari, L.; Margison, G.P.; Pein, F.
Dose finding and O6-alkylguanine-DNA alkyltransferase study of cisplatin combined with temozolomide in paediatric solid malignancies
Br. J. Cancer
93
529-537
2005
Homo sapiens
Manually annotated by BRENDA team
Blough, M.D.; Zlatescu, M.C.; Cairncross, J.G.
O6-methylguanine-DNA methyltransferase regulation by p53 in astrocytic cells
Cancer Res.
67
580-584
2007
Homo sapiens, Mus musculus
Manually annotated by BRENDA team
Loeber, R.; Rajesh, M.; Fang, Q.; Pegg, A.E.; Tretyakova, N.
Cross-linking of the human DNA repair protein O6-alkylguanine DNA alkyltransferase to DNA in the presence of 1,2,3,4-diepoxybutane
Chem. Res. Toxicol.
19
645-654
2006
Homo sapiens
Manually annotated by BRENDA team
Liu, L.; Watanabe, K.; Fang, Q.; Williams, K.M.; Guengerich, F.P.; Pegg, A.E.
Effect of alterations of key active site residues in O6-alkylguanine-DNA Alkyltransferase on its ability to modulate the genotoxicity of 1,2-dibromoethane
Chem. Res. Toxicol.
20
155-163
2007
Homo sapiens
Manually annotated by BRENDA team
Juillerat, A.; Heinis, C.; Sielaff, I.; Barnikow, J.; Jaccard, H.; Kunz, B.; Terskikh, A.; Johnsson, K.
Engineering substrate specificity of O6-alkylguanine-DNA alkyltransferase for specific protein labeling in living cells
Chembiochem
6
1263-1269
2005
Homo sapiens (P16455), Homo sapiens
Manually annotated by BRENDA team
Sabharwal, A.; Middleton, M.R.
Exploiting the role of O6-methylguanine-DNA-methyltransferase (MGMT) in cancer therapy
Curr. Opin. Pharmacol.
6
355-363
2006
Escherichia coli, Homo sapiens, Mus musculus, Rattus norvegicus
Manually annotated by BRENDA team
Povey, A.C.; ODonnell, P.; Barber, P.; Watson, M.; Margison, G.P.; Santibanez Koref, M.F.
Smoking is associated with a decrease of O6-alkylguanine-DNA alkyltransferase activity in bronchial epithelial cells
Int. J. Cancer
119
463-466
2006
Homo sapiens
Manually annotated by BRENDA team
Schwarzl, S.M.; Smith, J.C.; Kaina, B.; Efferth, T.
Molecular modeling of O6-methylguanine-DNA methyltransferase mutant proteins encoded by single nucleotide polymorphisms
Int. J. Mol. Med.
16
553-557
2005
Homo sapiens (P16455)
Manually annotated by BRENDA team
Pagani, E.; Falcinelli, S.; Pepponi, R.; Turriziani, M.; Caporaso, P.; Caporali, S.; Bonmassar, E.; DAtri, S.
Combined effect of temozolomide and hyperthermia on human melanoma cell growth and O6-methylguanine-DNA methyltransferase activity
Int. J. Oncol.
30
443-451
2007
Homo sapiens
Manually annotated by BRENDA team
Zang, H.; Fang, Q.; Pegg, A.E.; Guengerich, F.P.
Kinetic analysis of steps in the repair of damaged DNA by human O6-alkylguanine-DNA alkyltransferase
J. Biol. Chem.
280
30873-30881
2005
Homo sapiens
Manually annotated by BRENDA team
Rasimas, J.J.; Kar, S.R.; Pegg, A.E.; Fried, M.G.
Interactions of human O6-alkylguanine-DNA alkyltransferase (AGT) with short single-stranded DNAs
J. Biol. Chem.
282
3357-3366
2007
Homo sapiens (P16455), Homo sapiens
Manually annotated by BRENDA team
Kuo, C.C.; Liu, J.F.; Chang, J.Y.
DNA repair enzyme, O6-methylguanine DNA methyltransferase, modulates cytotoxicity of camptothecin-derived topoisomerase I inhibitors
J. Pharmacol. Exp. Ther.
316
946-954
2006
Homo sapiens
Manually annotated by BRENDA team
Maxwell, J.A.; Johnson, S.P.; Quinn, J.A.; McLendon, R.E.; Ali-Osman, F.; Friedman, A.H.; Herndon, J.E.; Bierau, K.; Bigley, J.; Bigner, D.D.; Friedman, H.S.
Quantitative analysis of O6-alkylguanine-DNA alkyltransferase in malignant glioma
Mol. Cancer Ther.
5
2531-2539
2006
Homo sapiens
Manually annotated by BRENDA team
Pearson, S.J.; Ferguson, J.; Santibanez-Koref, M.; Margison, G.P.
Inhibition of O6-methylguanine-DNA methyltransferase by an alkyltransferase-like protein from Escherichia coli
Nucleic Acids Res.
33
3837-3844
2005
Homo sapiens (P16455), Homo sapiens
Manually annotated by BRENDA team
Shibata, T.; Glynn, N.; McMurry, T.B.; McElhinney, R.S.; Margison, G.P.; Williams, D.M.
Novel synthesis of O6-alkylguanine containing oligodeoxyribonucleotides as substrates for the human DNA repair protein, O6-methylguanine DNA methyltransferase (MGMT)
Nucleic Acids Res.
34
1884-1891
2006
Homo sapiens
Manually annotated by BRENDA team
Gronemeyer, T.; Chidley, C.; Juillerat, A.; Heinis, C.; Johnsson, K.
Directed evolution of O6-alkylguanine-DNA alkyltransferase for applications in protein labeling
Protein Eng. Des. Sel.
19
309-316
2006
Homo sapiens
Manually annotated by BRENDA team
Verbeek, B.; Southgate, T.D.; Gilham, D.E.; Margison, G.P.
O6-Methylguanine-DNA methyltransferase inactivation and chemotherapy
Br. Med. Bull.
85
17-33
2008
Homo sapiens
Manually annotated by BRENDA team
McMurry, T.B.
MGMT inhibitors--The Trinity College-Paterson Institute experience, a chemists perception
DNA Repair
6
1161-1169
2007
Homo sapiens
Manually annotated by BRENDA team
Jeuken, J.W.; Cornelissen, S.J.; Vriezen, M.; Dekkers, M.M.; Errami, A.; Sijben, A.; Boots-Sprenger, S.H.; Wesseling, P.
MS-MLPA: an attractive alternative laboratory assay for robust, reliable, and semiquantitative detection of MGMT promoter hypermethylation in gliomas
Lab. Invest.
87
1055-1065
2007
Homo sapiens
Manually annotated by BRENDA team
Hu, J.; Ma, A.; Dinner, A.R.
A two-step nucleotide-flipping mechanism enables kinetic discrimination of DNA lesions by AGT
Proc. Natl. Acad. Sci. USA
105
4615-4620
2008
Homo sapiens (P16455)
Manually annotated by BRENDA team
Sasai, K.; Nodagashira, M.; Nishihara, H.; Aoyanagi, E.; Wang, L.; Katoh, M.; Murata, J.; Ozaki, Y.; Ito, T.; Fujimoto, S.; Kaneko, S.; Nagashima, K.; Tanaka, S.
Careful exclusion of non-neoplastic brain components is required for an appropriate evaluation of O6-methylguanine-DNA methyltransferase status in glioma: relationship between immunohistochemistry and methylation analysis
Am. J. Surg. Pathol.
32
1220-1227
2008
Homo sapiens
Manually annotated by BRENDA team
Lee, S.M.; Lee, E.J.; Ko, Y.H.; Lee, S.H.; Maeng, L.; Kim, K.M.
Prognostic significance of O6-methylguanine DNA methyltransferase and p57 methylation in patients with diffuse large B-cell lymphomas
APMIS
117
87-94
2009
Homo sapiens
Manually annotated by BRENDA team
Hermes, M.; Geisler, H.; Osswald, H.; Riehle, R.; Kloor, D.
Alterations in S-adenosylhomocysteine metabolism decrease O6-methylguanine DNA methyltransferase gene expression without affecting promoter methylation
Biochem. Pharmacol.
75
2100-2111
2008
Homo sapiens
Manually annotated by BRENDA team
Billson, H.A.; Harrison, K.L.; Lees, N.P.; Hall, C.N.; Margison, G.P.; Povey, A.C.
Dietary variables associated with DNA N7-methylguanine levels and O6-alkylguanine DNA-alkyltransferase activity in human colorectal mucosa
Carcinogenesis
30
615-620
2009
Homo sapiens
Manually annotated by BRENDA team
Quiros, S.; Roos, W.P.; Kaina, B.
Processing of O6-methylguanine into DNA double-strand breaks requires two rounds of replication whereas apoptosis is also induced in subsequent cell cycles
Cell Cycle
9
168-178
2010
Homo sapiens
Manually annotated by BRENDA team
Lai, J.C.; Cheng, Y.W.; Goan, Y.G.; Chang, J.T.; Wu, T.C.; Chen, C.Y.; Lee, H.
Promoter methylation of O(6)-methylguanine-DNA-methyltransferase in lung cancer is regulated by p53
DNA Repair
7
1352-1363
2008
Homo sapiens
Manually annotated by BRENDA team
Nakajima, T.; Yamada, Y.; Shimoda, T.; Matsubara, J.; Kato, K.; Hamaguchi, T.; Shimada, Y.; Okayama, Y.; Oka, T.; Shirao, K.
Combination of O6-methylguanine-DNA methyltransferase and thymidylate synthase for the prediction of fluoropyrimidine efficacy
Eur. J. Cancer
44
400-407
2008
Homo sapiens
Manually annotated by BRENDA team
Kim, J.I.; Suh, J.T.; Choi, K.U.; Kang, H.J.; Shin, D.H.; Lee, I.S.; Moon, T.Y.; Kim, W.T.
Inactivation of O6-methylguanine-DNA methyltransferase in soft tissue sarcomas: association with K-ras mutations
Hum. Pathol.
40
934-941
2009
Homo sapiens
Manually annotated by BRENDA team
Nagasaka, T.; Goel, A.; Notohara, K.; Takahata, T.; Sasamoto, H.; Uchida, T.; Nishida, N.; Tanaka, N.; Boland, C.R.; Matsubara, N.
Methylation pattern of the O6-methylguanine-DNA methyltransferase gene in colon during progressive colorectal tumorigenesis
Int. J. Cancer
122
2429-2436
2008
Homo sapiens
Manually annotated by BRENDA team
Fang, Q.; Kanugula, S.; Tubbs, J.L.; Tainer, J.A.; Pegg, A.E.
Repair of O4-alkylthymine by O6-alkylguanine-DNA alkyltransferases
J. Biol. Chem.
285
8185-8195
2009
Escherichia coli, Homo sapiens (P16455)
Manually annotated by BRENDA team
Buccoliero, A.M.; Castiglione, F.; Rossi DeglInnocenti, D.; Paglierani, M.; Maio, V.; Gheri, C.F.; Garbini, F.; Moncini, D.; Taddei, A.; Sardi, I.; Sanzo, M.; Giordano, F.; Mussa, F.; Genitori, L.; Taddei, G.L.
O6-methylguanine-DNA-methyltransferase in recurring anaplastic ependymomas: PCR and immunohistochemistry
J. Chemother.
20
263-268
2008
Homo sapiens
Manually annotated by BRENDA team
Parkinson, J.; Wheeler, H.; Clarkson, A.; McKenzie, C.; Biggs, M.; Little, N.; Cook, R.; Messina, M.; Robinson, B.; McDonald, K.
Variation of O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation in serial samples in glioblastoma
J. Neurooncol.
87
71-78
2008
Homo sapiens
Manually annotated by BRENDA team
Jena, N.R.; Shukla, P.K.; Jena, H.S.; Mishra, P.C.; Suhai, S.
O6-methylguanine repair by O6-alkylguanine-DNA alkyltransferase
J. Phys. Chem. B
113
16285-16290
2009
Homo sapiens (P16455)
Manually annotated by BRENDA team
Sabharwal, A.; Waters, R.; Danson, S.; Clamp, A.; Lorigan, P.; Thatcher, N.; Margison, G.P.; Middleton, M.R.
Predicting the myelotoxicity of chemotherapy: the use of pretreatment O6-methylguanine-DNA methyltransferase determination in peripheral blood mononuclear cells
Melanoma Res.
21
502-508
2011
Homo sapiens
Manually annotated by BRENDA team
Zheng, M.; Bocangel, D.; Ramesh, R.; Ekmekcioglu, S.; Poindexter, N.; Grimm, E.A.; Chada, S.
Interleukin-24 overcomes temozolomide resistance and enhances cell death by down-regulation of O6-methylguanine-DNA methyltransferase in human melanoma cells
Mol. Cancer Ther.
7
3842-3851
2008
Homo sapiens
Manually annotated by BRENDA team
Zhong, Y.; Huang, Y.; Huang, Y.; Zhang, T.; Ma, C.; Zhang, S.; Fan, W.; Chen, H.; Qian, J.; Lu, D.
Effects of O6-methylguanine-DNA methyltransferase (MGMT) polymorphisms on cancer: a meta-analysis
Mutagenesis
25
83-95
2010
Homo sapiens
Manually annotated by BRENDA team
Remington, M.; Chtchetinin, J.; Ancheta, K.; Nghiemphu, P.L.; Cloughesy, T.; Lai, A.
The L84F polymorphic variant of human O6-methylguanine-DNA methyltransferase alters stability in U87MG glioma cells but not temozolomide sensitivity
Neuro-oncology
11
22-32
2009
Homo sapiens
Manually annotated by BRENDA team
Robinson, C.; Palomo, J.; Vogelbaum, M.A.
Thin layer chromatography-based assay of O6-methylguanine-DNA methyltransferase activity in tissue
Anal. Biochem.
405
263-265
2010
Homo sapiens
Manually annotated by BRENDA team
Lin, J.W.; Wu, Y.T.; Chang, I.W.
The prognostic impact of O6-methylguanine DNA methyltransferase and epidermal growth factor receptor expressions on primary gliosarcoma: a clinicopathologic and immunohistochemical study of seven cases at a single institution
Indian J. Pathol. Microbiol.
54
683-687
2012
Homo sapiens
Manually annotated by BRENDA team
Skorvaga, M.; Raven, N.D.; Margison, G.P.
Thermostable archaeal O6-alkylguanine-DNA alkyltransferases
Proc. Natl. Acad. Sci. USA
95
6711-6715
1998
Escherichia coli, Homo sapiens, Pyrobaculum islandicum, Pyrococcus furiosus, Sulfolobus acidocaldarius, Thermococcus litoralis, Escherichia coli BS21
Manually annotated by BRENDA team
Hongo, A.; Gu, R.; Suzuki, M.; Nemoto, N.; Nishigaki, K.
A radioisotope-nondependent high-sensitivity method for measuring the activity of glioblastoma-related O6-methylguanine DNA methyltransferase
Anal. Biochem.
480
82-84
2015
Homo sapiens
Manually annotated by BRENDA team
Fahrer, J.; Kaina, B.
O6-methylguanine-DNA methyltransferase in the defense against N-nitroso compounds and colorectal cancer
Carcinogenesis
34
2435-2442
2013
Homo sapiens
Manually annotated by BRENDA team
Chahal, M.; Abdulkarim, B.; Xu, Y.; Guiot, M.C.; Easaw, J.C.; Stifani, N.; Sabri, S.
O6-Methylguanine-DNA methyltransferase is a novel negative effector of invasion in glioblastoma multiforme
Mol. Cancer Ther.
11
2440-2450
2012
Homo sapiens
Manually annotated by BRENDA team
Senthong, P.; Millington, C.L.; Wilkinson, O.J.; Marriott, A.S.; Watson, A.J.; Reamtong, O.; Eyers, C.E.; Williams, D.M.; Margison, G.P.; Povey, A.C.
The nitrosated bile acid DNA lesion O6-carboxymethylguanine is a substrate for the human DNA repair protein O6-methylguanine-DNA methyltransferase
Nucleic Acids Res.
41
3047-3055
2013
Homo sapiens
Manually annotated by BRENDA team
Li, X.; Qian, S.; Zheng, L.; Yang, B.; He, Q.; Hu, Y.
A mechanism-based fluorescent probe for labeling O6-methylguanine-DNA methyltransferase in live cells
Org. Biomol. Chem.
10
3189-3191
2012
Homo sapiens
Manually annotated by BRENDA team
Kishida, Y.; Natsume, A.; Toda, H.; Toi, Y.; Motomura, K.; Koyama, H.; Matsuda, K.; Nakayama, O.; Sato, M.; Suzuki, M.; Kondo, Y.; Wakabayashi, T.
Correlation between quantified promoter methylation and enzymatic activity of O6-methylguanine-DNA methyltransferase in glioblastomas
Tumour Biol.
33
373-381
2012
Homo sapiens
Manually annotated by BRENDA team
Thirumal Kumar, D.; Mendonca, E.; Priyadharshini Christy, J.; George Priya Doss, C.; Zayed, H.
A computational model to predict the structural and functional consequences of missense mutations in O6-methylguanine DNA methyltransferase
Adv. Protein Chem. Struct. Biol.
115
351-369
2019
Homo sapiens (P16455)
Manually annotated by BRENDA team
Girot, P.; Dumars, C.; Mosnier, J.F.; Muzellec, L.; Senellart, H.; Foubert, F.; Caroli-Bosc, F.X.; Cauchin, E.; Regenet, N.; Matysiak-Budnik, T.; Touchefeu, Y.
Short article Evaluation of O6-methylguanine-DNA methyltransferase as a predicting factor of response to temozolomide-based chemotherapy in well-differentiated metastatic pancreatic neuroendocrine tumors
Eur. J. Gastroenterol. Hepatol.
29
826-830
2017
Homo sapiens (P16455), Homo sapiens
Manually annotated by BRENDA team
Cabrini, G.; Fabbri, E.; Lo Nigro, C.; Dechecchi, M.C.; Gambari, R.
Regulation of expression of O6-methylguanine-DNA methyltransferase and the treatment of glioblastoma (Review)
Int. J. Oncol.
47
417-428
2015
Homo sapiens
Manually annotated by BRENDA team
Kurimoto, T.; Kondo, A.; Ogino, I.; Fujimura, J.; Arakawa, A.; Arai, H.; Shimizu, T.
Effect of O6-methylguanine-DNA methyltransferase methylation in medulloblastoma
Mol. Clin. Oncol.
7
1107-1111
2017
Homo sapiens (P16455)
Manually annotated by BRENDA team
Zhao, Y.; Xiao, Z.; Chen, W.; Yang, J.; Li, T.; Fan, B.
Disulfiram sensitizes pituitary adenoma cells to temozolomide by regulating O6-methylguanine-DNA methyltransferase expression
Mol. Med. Rep.
12
2313-2322
2015
Homo sapiens
Manually annotated by BRENDA team
Chikan, N.A.; Bukhari, S.; Shabir, N.; Amin, A.; Shafi, S.; Qadri, R.A.; Patel, T.N.
Atomic insight into the altered O6-methylguanine-DNA methyltransferase protein architecture in gastric cancer
PLoS ONE
10
e0127741
2015
Homo sapiens (P16455), Homo sapiens
Manually annotated by BRENDA team
Franceschi, E.; Tosoni, A.; Minichillo, S.; Depenni, R.; Paccapelo, A.; Bartolini, S.; Michiara, M.; Pavesi, G.; Urbini, B.; Crisi, G.; Cavallo, M.A.; Tosatto, L.; Dazzi, C.; Biasini, C.; Pasini, G.; Balestrini, D.; Zanelli, F.; Ramponi, V.; Fioravanti, A.; Giombelli, E.; De Biase, D.; Baruzzi, A.
The prognostic roles of gender and O6-methylguanine-DNA methyltransferase methylation status in glioblastoma patients The female power
World Neurosurg.
112
e342-e347
2018
Homo sapiens
Manually annotated by BRENDA team
Yang, L.; Li, W.; Zhao, Y.; Zhong, S.; Wang, X.; Jiang, S.; Cheng, Y.; Xu, H.; Zhao, G.
Computational study of novel natural inhibitors targeting O6-methylguanine-DNA methyltransferase
World Neurosurg.
130
e294-e306
2019
Homo sapiens
Manually annotated by BRENDA team