3-methyladenine-DNA glycosylase II: the crystal structure of an AlkA-hypoxanthine complex suggests the possibility of product inhibition

Bioconjug Chem. 2002 May-Jun;13(3):403-7. doi: 10.1021/bc015527v.

Abstract

Escherichia coli (E. coli) protein 3-methyladenine-DNA glycosylase II (AlkA) functions primarily by removing alkylation damage from duplex and single stranded DNA. A crystal structure of AlkA was refined to 2.0 A resolution. This structure in turn was used to refine an AlkA-hypoxanthine (substrate) complex structure to 2.4 A resolution. The complex structure shows hypoxanthine located in AlkA's active site stacked between residues W218 and Y239. The structural analysis of the AlkA and AlkA-hypoxanthine structures indicate that free hypoxanthine binding in the active site may inhibit glycosylase activity.

MeSH terms

  • Crystallization
  • DNA Glycosylases*
  • Enzyme Inhibitors / pharmacology
  • Escherichia coli / enzymology*
  • Escherichia coli / genetics
  • Hypoxanthines / chemistry*
  • Models, Molecular
  • N-Glycosyl Hydrolases / antagonists & inhibitors
  • N-Glycosyl Hydrolases / chemistry*
  • N-Glycosyl Hydrolases / metabolism
  • Tryptophan / chemistry
  • Tyrosine / chemistry
  • X-Ray Diffraction

Substances

  • Enzyme Inhibitors
  • Hypoxanthines
  • Tyrosine
  • Tryptophan
  • DNA Glycosylases
  • N-Glycosyl Hydrolases
  • DNA-3-methyladenine glycosidase II