O⁶-Methylguanine-DNA Methyltransferase human

O⁶-Methylguanine-DNA methyl transferase (MGMT), containing 207 amino acids, is a ubiquitous DNA repair enzyme that removes O⁶-alkyl-guanine, primarily O⁶-methylguanine, lesions from damaged DNA.

O⁶-Methylguanine-DNA methyl transferase (MGMT), containing 207 amino acids, is a ubiquitous DNA repair enzyme that removes O⁶-alkyl-guanine, primarily O⁶-methylguanine, lesions from damaged DNA. It is a major contributor to cellular protection from the mutagenic, carcinogenic, and cytotoxic effects of DNA alkylation. Its action is based on the transfer of the alkyl group from the DNA to a unique acceptor cysteine residue in the protein, forming a stable thioether linkage. The cysteine sulfhydryl moiety is not regenerated and therefore, MGMT is frequently classified as a suicide enzyme. Since the reaction irreversibly inactivates the enzyme, the repair capacity for O⁶-methylguanine is dependent on the number of MGMT molecules in the cell. There is a correlation between the occurrence of cancer in various tissues and the lack of the MGMT enzyme. High levels of MGMT result in reduced tumor events and resistance of tumors to alkylating agents.

One unit is the amount of protein that removes 50% of the methyl groups of 0.5 pmol double stranded DNA oligonucleotide substrate containing an O⁶-methylguanine in 10 minutes at 37 °C.

Solution in 50% glycerol containing 20 mM Tris, pH 7.5, 1 mM EDTA, 200 mM NaCl, and 1 mM DTT.