Recognition of the nonpolar base 4-methylindole in DNA by the DNA repair adenine glycosylase MutY

Org Lett. 2000 May 4;2(9):1341-4. doi: 10.1021/ol005831o.

Abstract

[formula: see text] The DNA repair adenine glycosylase MutY efficiently recognizes 7-deaza-2'-deoxyadenosine (Z) and its nonpolar isostere 4-methylindole beta-deoxynucleoside (M) opposite 7,8-dihydro-8-oxo-2'-deoxyguanosine (OG) and G in DNA. Both wild-type and truncated MutY exhibit a 10- to 20-fold higher affinity for a duplex containing OG:M than OG:Z. More efficient recognition of M over Z by MutY may be to due the lack of hydrogen bonding with the OG that facilitates nucleotide flipping during the substrate recognition process.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 8-Hydroxy-2'-Deoxyguanosine
  • DNA / chemistry
  • DNA / metabolism*
  • DNA Glycosylases*
  • DNA Repair
  • Deoxyguanosine / analogs & derivatives
  • Deoxyguanosine / chemistry
  • Deoxyguanosine / metabolism
  • Guanosine / metabolism
  • Indoles / metabolism*
  • N-Glycosyl Hydrolases / chemistry
  • N-Glycosyl Hydrolases / metabolism*
  • Nucleic Acid Heteroduplexes
  • Nucleosides / metabolism*

Substances

  • 4-methylindole deoxynucleoside
  • Indoles
  • Nucleic Acid Heteroduplexes
  • Nucleosides
  • Guanosine
  • 8-Hydroxy-2'-Deoxyguanosine
  • DNA
  • DNA Glycosylases
  • N-Glycosyl Hydrolases
  • mutY adenine glycosylase
  • Deoxyguanosine