PMID:10946229

Citation	Hollis, T, Lau, A and Ellenberger, T (2000) Structural studies of human alkyladenine glycosylase and E. coli 3-methyladenine glycosylase. Mutat. Res. 460:201-10
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.
Links	PubMed
Keywords	Alkylation; Bacterial Proteins/chemistry; Bacterial Proteins/physiology; Binding Sites; Catalysis; DNA/chemistry; DNA/metabolism; DNA Damage; DNA Glycosylases; DNA Repair; Escherichia coli/enzymology; Humans; Hydrogen Bonding; Methylation; Models, Molecular; N-Glycosyl Hydrolases/chemistry; N-Glycosyl Hydrolases/physiology; Nucleic Acid Conformation; Protein Conformation; Structure-Activity Relationship; Substrate Specificity
edit table

Significance

You can help EcoliWiki by summarizing why this paper is useful

Useful Materials and Methods

You can help Ecoliwiki by describing the useful materials (strains, plasmids, antibodies, etc) described in this paper.

Annotations

<annotationlinks/>

EcoliWiki Links

Add links to pages that link here (e.g. gene, product, method pages)

References

See Help:References for how to manage references in EcoliWiki.