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PMID:6765195
| Citation |
Lindahl, T, Demple, B and Robins, P (1982) Suicide inactivation of the E. coli O6-methylguanine-DNA methyltransferase. EMBO J. 1:1359-63 |
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| Abstract |
The O6-methylguanine-DNA methyltransferase of Escherichia coli acts rapidly and stoichiometrically to convert a mutagenic O6-methylguanine residue in DNA to unsubstituted guanine. Even at low protein concentrations and in the absence of any cofactors, the transfer of a methyl group to one of the protein's own cysteine residues occurs in less than 2 s at 37 degrees C. The entire kinetic process can be followed experimentally at 5 degrees C. Formation of S-methylcysteine in the protein is accompanied by loss of activity and accounts for the exceptional suicide kinetics of this enzyme as well as for the sharp saturation of O6-methylguanine repair observed in vivo. The enzyme can remove greater than 98% of the methyl groups from O6-methylguanine present in alkylated DNA, but leaves N-alkylated purines untouched. Single-stranded DNA containing O6-methylguanine is a poor substrate, with the methyl transfer occurring at approximately 0.1% of the rate for duplex DNA. This latter observation may explain the high frequency of mutations induced by alkylating agents at DNA replication forks. |
| Links | |
| Keywords |
Chromatography, High Pressure Liquid; DNA Repair; DNA Replication; DNA, Bacterial; Escherichia coli/enzymology; Kinetics; Methyltransferases/antagonists & inhibitors; Micrococcus; O(6)-Methylguanine-DNA Methyltransferase; Protein Binding |
Significance
Annotations
| Gene product | Qualifier | GO Term | Evidence Code | with/from | Aspect | Extension | Notes | Status |
|---|---|---|---|---|---|---|---|---|
|
involved_in |
GO:0080111: DNA demethylation |
ECO:0000314: direct assay evidence used in manual assertion |
P |
Seeded From UniProt |
complete | |||
|
involved_in |
GO:0018125: peptidyl-cysteine methylation |
ECO:0000314: direct assay evidence used in manual assertion |
P |
Seeded From UniProt |
complete | |||
|
enables |
GO:0003908: methylated-DNA-[protein]-cysteine S-methyltransferase activity |
ECO:0000314: direct assay evidence used in manual assertion |
F |
Seeded From UniProt |
complete | |||
Notes
See also
References
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