Abstract
Human alkyladenine glycosylase (AAG) and Escherichia coli 3-methyladenine glycosylase (AlkA) are base excision repair glycosylases that recognize and excise a variety of alkylated bases from DNA. The crystal structures of these enzymes have provided insight into their substrate specificity and mechanisms of catalysis. Both enzymes utilize DNA bending and base-flipping mechanisms to expose and bind substrate bases. Crystal structures of AAG complexed to DNA suggest that the enzyme selects substrate bases through a combination of hydrogen bonding and the steric constraints of the active site, and that the enzyme activates a water molecule for an in-line backside attack of the N-glycosylic bond. In contrast to AAG, the structure of the AlkA-DNA complex suggests that AlkA substrate recognition and catalytic specificity are intimately integrated in a S(N)1 type mechanism in which the catalytic Asp238 directly promotes the release of modified bases.
Original language | English (US) |
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Pages (from-to) | 201-210 |
Number of pages | 10 |
Journal | Mutation Research - DNA Repair |
Volume | 460 |
Issue number | 3-4 |
DOIs | |
State | Published - Aug 30 2000 |
Externally published | Yes |
Keywords
- AAG
- AlkA
- Base-flipping
- Glycosidase mechanism
- Protein-DNA complex
ASJC Scopus subject areas
- Molecular Biology
- Toxicology
- Genetics