Structural studies of human alkyladenine glycosylase and E. coli 3-methyladenine glycosylase

Thomas Hollis, Albert Lau, Tom Ellenberger

Research output: Contribution to journalArticlepeer-review

55 Scopus citations


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 languageEnglish (US)
Pages (from-to)201-210
Number of pages10
JournalMutation Research - DNA Repair
Issue number3-4
StatePublished - Aug 30 2000
Externally publishedYes


  • AAG
  • AlkA
  • Base-flipping
  • Glycosidase mechanism
  • Protein-DNA complex

ASJC Scopus subject areas

  • Molecular Biology
  • Toxicology
  • Genetics


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