2.1.1.63: methylated-DNA-[protein]-cysteine S-methyltransferase
This is an abbreviated version!
For detailed information about methylated-DNA-[protein]-cysteine S-methyltransferase, go to the full flat file.
Word Map on EC 2.1.1.63
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2.1.1.63
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glioblastoma
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temozolomide
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glioma
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o6-benzylguanine
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adduct
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resect
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hypermethylation
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methylation-specific
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radiotherapy
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unmethylated
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mismatch
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nitrosoureas
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isocitrate
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cpg
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n-methyl-n'-nitro-n-nitrosoguanidine
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multiforme
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chloroethylnitrosoureas
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progression-free
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1,3-bis2-chloroethyl-1-nitrosourea
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chloroethylating
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n-methyl-n-nitrosourea
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astrocytomas
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carmustine
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o6-meg
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interstrand
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glycosylase
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dna-repair
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anaplastic
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karnofsky
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dacarbazine
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repair-deficient
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tmz-induced
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methylnitrosourea
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phosphotriester
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n-nitroso
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myelosuppression
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chemoradiotherapy
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oligodendrogliomas
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tmz-resistant
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medicine
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procarbazine
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p14arf
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drug development
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diagnostics
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lomustine
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miscoding
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idh-mutant
-
analysis
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idh-wildtype
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dna-alkylating
-
repair-proficient
-
neuro-oncology
-
premutagenic
-
codeletion
-
molecular biology
- 2.1.1.63
- glioblastoma
- temozolomide
- glioma
- o6-benzylguanine
- adduct
-
resect
-
hypermethylation
-
methylation-specific
-
radiotherapy
-
unmethylated
- mismatch
-
nitrosoureas
- isocitrate
- cpg
- n-methyl-n'-nitro-n-nitrosoguanidine
- multiforme
-
chloroethylnitrosoureas
-
progression-free
-
1,3-bis2-chloroethyl-1-nitrosourea
-
chloroethylating
- n-methyl-n-nitrosourea
- astrocytomas
- carmustine
-
o6-meg
-
interstrand
- glycosylase
-
dna-repair
-
anaplastic
-
karnofsky
- dacarbazine
-
repair-deficient
-
tmz-induced
-
methylnitrosourea
-
phosphotriester
-
n-nitroso
-
myelosuppression
-
chemoradiotherapy
- oligodendrogliomas
-
tmz-resistant
- medicine
- procarbazine
-
p14arf
- drug development
- diagnostics
-
lomustine
-
miscoding
-
idh-mutant
- analysis
-
idh-wildtype
-
dna-alkylating
-
repair-proficient
-
neuro-oncology
-
premutagenic
-
codeletion
- molecular biology
Reaction
Synonyms
Ada protein, Ada-C, AGAT, AGT, AGTendoV, alkylated DNA-protein alkyltransferase, alkylguanine transferase, ATASE, C-hAGT, carboxyl terminal domain of the inducible Escherichia coli ada alkyltransferase, hAGT, methylated-DNA-[protein]-cysteine S-methyltransferase, methylguanine DNA methyltransferase, MGMT, Mgt1, MJ1529, 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 methyltransferase, O6-methylguanine-DNA methyltransferase, O6-methylguanine-DNA-methyltransferase, O6-MGMT, O6meG-DNA alkyltransferase, OGT, Pk-MGMT, SSO2487, Tk-MGMT, TTHA1564
ECTree
2.1.1.63 methylated-DNA-[protein]-cysteine S-methyltransferaseAdvanced search results
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results (Engineering
Engineering on EC 2.1.1.63 - methylated-DNA-[protein]-cysteine S-methyltransferase
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PROTEIN VARIANTS 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
V139F
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has an increased ability to protect against the cytotoxic and mutagenic effects of N-methyl-N'-nitro-N-nitrosoguanidine
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
A41D/S115T/I151N
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1.6fold increased activity, AGT mutant selected using yeast three-hybrid system
C145A
C145F
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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
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inactive mutant enzyme forms a specific and stable complex with a 6-O-methylguanine-containing oligonucleotide substrate
C24A
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mutation of Cys24 prevents the zinc-dependent alkyl transferase by N-terminal domain human AGT
C5A
D42E/A51T/A64V/K104M
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0.5fold increased activity, AGT mutant selected using yeast three-hybrid system
D42E/P47L/V155L/K178M
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1.9fold increased activity, AGT mutant selected using yeast three-hybrid system
E110D/L120M
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0.7fold increased activity, AGT mutant selected using yeast three-hybrid system
E25K
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0.7fold increased activity, AGT mutant selected using yeast three-hybrid system
E92D/I151V/R175W
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1.0fold increased activity, AGT mutant selected using yeast three-hybrid system
F79I/V88I/F89L
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0.7fold increased activity, AGT mutant selected using yeast three-hybrid system
G122C
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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
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mutant form expressed by the medulloblastoma cell line D283 MED, mutant enzyme is not easily inhibited by O6-benzylguanine
G160R
G160W
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cells overexpressing W160AGT do not become labeled, even when incubated with O6-propargylguanine for extended periods of time
H29A
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does not show the stability enehancement of wild-type hAGT with its intact zinc coordination sphere
H71Y/A154T
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3.3fold increased activity, AGT mutant selected using phage display
H85A
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does not show the stability enehancement of wild-type hAGT with its intact zinc coordination sphere
I143V
I143V/K178R
K104E/T127A/A154T
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4.5fold increased activity, AGT mutant selected using phage display
K107R/A154T
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4.7fold increased activity, AGT mutant selected using phage display
K165R
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does not abolish activity on 6-O-methylguanine but greatly reduces the ability to react with O6-benzylguanine
K165T
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mutant form expressed by the medulloblastoma cell line D341 MED, mutant enzyme is not easily inhibited by O6-benzylguanine
K8R/K104E/I151T
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1.4fold increased activity, AGT mutant selected using phage display
K8T/A51T/I112V/A154T
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5.5fold increased activity, AGT mutant selected using phage display
K8T/T127A/A154T/H174R
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5.8fold increased activity, AGT mutant selected using phage display
L33F/A68T
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2.1fold increased activity, AGT mutant selected using yeast three-hybrid system
L33F/N123Y
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2.2fold increased activity, AGT mutant selected using yeast three-hybrid system
L33F/V44A/V52A/A154T
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6.1fold increased activity, AGT mutant selected using phage display
L66M/K131R
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1.5fold increased activity, AGT mutant selected using yeast three-hybrid system
L84F
L84F/I143V/K178R
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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
N123V
no major structural change upon energy minimization, is within the DNA binding region and may therefore affect DNA binding of MGMT
N157/S159/C62A/C150N/G131K/G132T/M134L/R135S/Q115S/Q116H/K125A/A127T/R128A/S151I/S152N
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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
P140K
Q90R/K101N/F108I/V164L
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1.2fold increased activity, AGT mutant selected using yeast three-hybrid system
R128A
R128G
R128L
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reduces the AGT repair efficiency, smaller effects with the O6-benzylguanine substrate than the 6-O-methylguanine
R175L
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0.6fold increased activity, AGT mutant selected using yeast three-hybrid system
T11I/N67K/Q72L
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1.0fold increased activity, AGT mutant selected using yeast three-hybrid system
T38M/A41D/A64T/G173C
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0.8fold increased activity, AGT mutant selected using yeast three-hybrid system
V149I/A154T
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4.5fold increased activity, AGT mutant selected using phage display
V44G/V106A/I151T/A170T
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1.4fold increased activity, AGT mutant selected using yeast three-hybrid system
V46A/A50V/P58V/A154T
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3.4fold increased activity, AGT mutant selected using phage display
V52A/I151S/K178E
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2.3fold increased activity, AGT mutant selected using phage display
V52I/V164M
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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
P140K
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mutant confers resistance to N,N'-bis(2-chloroethyl)-N-nitrosourea and O(6)-benzylguanine
R37E
the mutant exhibits a 5fold lower affinity for the methylated duplex DNA compared to the wild type enzyme
R37K
the variant performs a sub-optimal alkylated-DNA repair in vitro compared to the wild type enzyme
R37L
T15S
the mutant exhibits a 2fold-lower affinity for double stranded methylated DNA compared to the wild type enzyme
Y139F
the mutant exhibits a 10fold lower affinity for the methylated duplex DNA compared to the wild type enzyme
C119F
the mutant shows reduced thermal stability compared to the wild type enzyme
C119L
the mutant shows reduced thermal stability compared to the wild type enzyme
D27A
the mutant shows reduced thermal stability compared to the wild type enzyme
D27K
the mutant shows reduced thermal stability compared to the wild type enzyme
C119F
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the mutant shows reduced thermal stability compared to the wild type enzyme
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C119L
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the mutant shows reduced thermal stability compared to the wild type enzyme
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D27A
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the mutant shows reduced thermal stability compared to the wild type enzyme
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D27K
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the mutant shows reduced thermal stability compared to the wild type enzyme
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E158A
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melting temperature of mutant enzyme E83A at 5 mM urea is 90.6°C, compared to 91.5°C for the wild-type enzyme
E159A
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melting temperature of mutant enzyme E83A at 5 mM urea is 91.7°C, compared to 91.5°C for the wild-type enzyme
E83A
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melting temperature of mutant enzyme E83A at 5 mM urea is 89.2°C, compared to 91.5°C for the wild-type enzyme
E93A
additional information
C145A
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inactive mutant enzyme forms a specific and stable complex with a 6-O-methylguanine-containing oligonucleotide substrate
C145A
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abolishes 1,2,3,4-diepoxybutane-induced cross-linking at this site, while the formation of conjugates via neighboring Cys150 is retained
C145A
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binds to alkylated DNA in a similar manner to wild type AGT but is unable to carry out the repair transfer, expressed in Escherichia coli, this mutant increases killing and mutagenesis by N-methyl-N'-nitro-N-nitrosoguanidine
C5A
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mutation of Cys5 prevents the zinc-dependent alkyl transferase by N-terminal domain human AGT
G156A
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mutant MGMT protein that is resistant to inactivators of the wild-type protein, used in myeloprotective gene therapy
G160R
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is as effective as wild-type in protecting cells from N-methyl-N'-nitro-N-nitrosoguanidine and N,N'-bis(2-chloroethyl)-N-nitrosourea, is strongly resistant to O6-benzylguanine
G160R
no major structural change upon energy minimization, is in the vicinity of the active Cys145 and may cause disturbances of O6-alkyl transfer from DNA to the protein
I143V
no major structural change upon energy minimization, is in the vicinity of the active Cys145 and may cause disturbances of O6-alkyl transfer from DNA to the protein, does not affect DNA repair capacity
I143V
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no significant association between the G allele of I143Val and cancer risk is found
I143V/K178R
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no significant effect on AGT activity, may be an increased risk for lung cancer in individuals with this change
I143V/K178R
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enhanced green fluorescent protein-tagged MGMT variants exhibit nuclear localization patterns indistinguishable from wild type enzyme
L84F
no major structural change upon energy minimization, may affect Zn2+ binding, does not affect DNA repair capacity
L84F
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a significant association is found between the T allele of L84F and cancer risk
L84F
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the L84F polymorphic variant of human O6-methylguanine-DNA methyltransferase alters stability in U87MG glioma cells but not temozolomide sensitivity, upon exposure to O6-benzylguanine, the L84F variant is degraded more rapidly than wild type
P140K
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95% reduced ability of the protein to react with Br(CH2)2Br as measured by loss of activity, no change in the stability of the AGT-Cys145S-(CH2)2Br intermediate
P140K
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mutant MGMT protein that is resistant to inactivators of the wild-type protein, used in myeloprotective gene therapy
R128A
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substantially reduced AGT-mediated increase in toxicity and the induction of mutations in Escherichia coli cells treated with Br(CH2)2Br, is able to react with Br(CH2)2Br at the Cys145 acceptor site, but the resulting AGT-Cys145S-(CH2)2Br is much less able to produce a covalent adduct with DNA
R128G
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reduces the AGT repair efficiency, no smaller effects with the O6-benzylguanine substrate than the 6-O-methylguanine
Y114A
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reduced ability of the protein to react with Br(CH2)2Br as measured by loss of activity
Y114E
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substantially reduced AGT-mediated increase in toxicity and the induction of mutations in Escherichia coli cells treated with Br(CH2)2Br
Y114F
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mutant form expressed by the medulloblastoma cell line Daoy, mutant enzyme is not easily inhibited by O6-benzylguanine
Y114F
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reduces the AGT repair efficiency, smaller effects with the O6-benzylguanine substrate than the 6-O-methylguanine
Y158H
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78% reduced ability of the protein to react with Br(CH2)2Br as measured by loss of activity, no change in the stability of the AGT-Cys145S-(CH2)2Br intermediate
R37L
the mutant exhibits a 10fold-lower affinity for double stranded methylated DNA compared to the wild type enzyme
R37L
the variant performs a sub-optimal alkylated-DNA repair in vitro compared to the wild type enzyme
E93A
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mutant enzyme unfolds one order of magnitude faster than does the wild-type enzyme
E93A
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stability against organic solvents does not differ from that of the wild-type enzyme
additional information
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deletion of more than 8 or 31 residues from the amino or carboxyl terminus, respectively, leads to the loss of both activity and substrate binding. Removal of Arg9 or Leu176 and distal residues inactivates the protein
additional information
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three allelic variants: V1 with amino acid substitution Leu84Phe, variant V2 with amino acid substitution Trp65Cys and variant V3 with a silent mutation. Wild-type and V1 variant have similar enzymatic and physicochemical properties, while variant V2 is considered to be unstable and rare
additional information
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the 28-amino acid carboxy-terminal tail of the enzyme is not required for activity and modulates the rate of 6-O-methylguanine DNA methyltransferase repair at reduced temperatures and plays a role in substrate specificity
additional information
AGT mutants resistant to inactivation by N9-cyclopentyl-O6-(4-bromothenyl)guanine
additional information
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AGT mutants resistant to inactivation by N9-cyclopentyl-O6-(4-bromothenyl)guanine
additional information
examination of the structural changes accompanying single nucleotide polymorphisms-related amino-acid changes in the MGMT protein
additional information
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insertion of random amino acid loops into the protein backbone reveals mutants that react with the non-natural substrate O6-propargylguanine, libraries generated by conventional random or targeted saturation mutagenesis, by contrast, do not yield any mutants with activity towards this new substrate
additional information
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MAGT decreased activity can be restored by combination of saturation mutagenesis of residues 150-154 and 31-35 from phage display and yeast three-hybrid system selections, reveals a mutant with 17fold higher activity than MAGT and a 52fold higher activity than wild-type AGT, is the most active AGT mutant against O6-benzylguanine derivatives described so far
additional information
MGMT W145 mutant does not inhibit methyl transfer by wild-type MGMT under the assay conditions used
additional information
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MGMT W145 mutant does not inhibit methyl transfer by wild-type MGMT under the assay conditions used
additional information
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mutation of Arg-128 to Ala greatly reduces the ability of AGT to repair O6-methylguanine in DNA but has no effect on the alkyl transfer reaction when the free base substrate, O6-benzylguanine is used, stability of AGT is reduced by most mutations at Lys-165
additional information
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no differences in protein levels and catalytic activity of topoisomerase I between MGMT-proficient and MGMT-deficient cells from the Tet-On-inducible and small interfering RNA systems
additional information
construct human AGT-03 (where AGT sequence -V149CSSGAVGN157- is replaced with the corresponding Ogt -I143GRNGTMTG151-), exhibits enhanced DNA containing 4-O-methylthymine repair activity in vitro compared to wild type AGT
additional information
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MGMT deficiency does not result in greater mutation frequency following cyclophosphamide or 1,3-bis (2-chloroethyl)-1-nitrosourea compared with wild-type mice
additional information
the H5 variant harbouring five mutations (in the helix-turn helix motif) has a catalytic activity on O-6-benzyl guanine derivated substrates, whereas its ability to bind and repair the natural DNA containing 6-O-methylguanine is completely abolished
additional information
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the H5 variant harbouring five mutations (in the helix-turn helix motif) has a catalytic activity on O-6-benzyl guanine derivated substrates, whereas its ability to bind and repair the natural DNA containing 6-O-methylguanine is completely abolished
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