InterPro domain: IPR003180

Methylpurine-DNA glycosylase (MPG, or alkyladenine DNA glycosylase (AAG)) is a base excision-repair protein, catalyzing the first step in base excision repair by cleaving damaged DNA bases within double-stranded DNA to produce an abasic site. MPG bends DNA by intercalating between the base pairs, causing the damaged base to flip out of the double helix and into the enzyme active site for cleavage. It is responsible for the hydrolysis of the deoxyribose N-glycosidic bond, excising 3-methyladenine and 3-methylguanine from damaged DNA [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 ]. Its action is induced by alkylating chemotherapeutics, as well as deaminated and lipid peroxidation-induced purine adducts [ 12 ]. MPG without an N-terminal extension excises hypoxanthine with one-third of the efficiency of full-length MPG under similar conditions, suggesting that is function may largely be attributable to the N-terminal extension [ 13 ].

Although AAG represents one of six DNA glycosylase classes, it lacks the helix-hairpin-helix active site motif associated with other base excision repair glycosylases and is structurally distinct from them.

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2. 3-methyladenine DNA glycosylases: structure, function, and biological importance. Bioessays 21, 668-76
3. Crystallizing thoughts about DNA base excision repair. Prog. Nucleic Acid Res. Mol. Biol. 68, 305-14
4. Crystal structure of a human alkylbase-DNA repair enzyme complexed to DNA: mechanisms for nucleotide flipping and base excision. Cell 95, 249-58
5. Molecular basis for discriminating between normal and damaged bases by the human alkyladenine glycosylase, AAG. Proc. Natl. Acad. Sci. U.S.A. 97, 13573-8
6. Human alkyladenine DNA glycosylase uses acid-base catalysis for selective excision of damaged purines. Biochemistry 42, 12418-29
7. Dissecting the broad substrate specificity of human 3-methyladenine-DNA glycosylase. J. Biol. Chem. 279, 9750-7
8. The efficiency of hypoxanthine excision by alkyladenine DNA glycosylase is altered by changes in nearest neighbor bases. DNA Repair (Amst.) 4, 1088-98
9. Effects of hydrogen bonding within a damaged base pair on the activity of wild type and DNA-intercalating mutants of human alkyladenine DNA glycosylase. J. Biol. Chem. 277, 31673-8
10. Methylated DNA-binding domain 1 and methylpurine-DNA glycosylase link transcriptional repression and DNA repair in chromatin. Proc. Natl. Acad. Sci. U.S.A. 100, 12859-64
11. Active-site clashes prevent the human 3-methyladenine DNA glycosylase from improperly removing bases. Chem. Biol. 9, 1033-41
12. Discrimination of lesion removal of N-methylpurine-DNA glycosylase revealed by a potent neutralizing monoclonal antibody. DNA Repair (Amst.) 7, 31-9
13. N-terminal extension of N-methylpurine DNA glycosylase is required for turnover in hypoxanthine excision reaction. J. Biol. Chem. 282, 30078-84