Crystal structure of DNA polymerase β with DNA containing the base lesion spiroiminodihydantoin in a templating position

Biochemistry. 2014 Apr 8;53(13):2075-7. doi: 10.1021/bi500270e. Epub 2014 Mar 26.

Abstract

The first high-resolution crystal structure of spiroiminodihydantoin (dSp1) was obtained in the context of the DNA polymerase β active site and reveals two areas of significance. First, the structure verifies the recently determined S configuration at the spirocyclic carbon. Second, the distortion of the DNA duplex is similar to that of the single-oxidation product 8-oxoguanine. For both oxidized lesions, adaptation of the syn conformation results in similar backbone distortions in the DNA duplex. The resulting conformation positions the dSp1 A-ring as the base-pairing face whereas the B-ring of dSp1 protrudes into the major groove.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Crystallography, X-Ray
  • DNA / chemistry*
  • DNA / metabolism
  • DNA Polymerase beta / chemistry*
  • DNA Polymerase beta / metabolism
  • Guanosine / analogs & derivatives*
  • Guanosine / chemistry
  • Guanosine / metabolism
  • Humans
  • Models, Molecular
  • Spiro Compounds / chemistry
  • Spiro Compounds / metabolism*
  • Templates, Genetic

Substances

  • Spiro Compounds
  • spiroiminodihydantoin
  • Guanosine
  • DNA
  • DNA Polymerase beta