Structural characterization of the Fpg family of DNA glycosylases

Dmitry O. Zharkov, Gil Shoham, Arthur P. Grollman*

*Corresponding author for this work

Research output: Contribution to journalShort surveypeer-review

129 Scopus citations

Abstract

Until recently, the Fpg family was the only major group of DNA glycosylases for which no structural data existed. Prototypical members of this family, found in eukaryotes as well as prokaryotes, have now been crystallized as free proteins and as complexes with DNA. In this review, we analyze the available structural information for formamidopyrimidine-DNA glycosylase (Fpg) and endonuclease VIII (Nei). Special emphasis is placed on mechanisms by which these enzymes recognize and selectively excise cognate lesions from oxidatively damaged DNA. The problem of lesion recognition is considered in two parts: how the enzyme efficiently locates a single lesion embedded in a vast excess of DNA; and how the lesion is accommodated in a pocket near the active site of the enzyme. Although all crystal structures reported to date for the Fpg family lack the damaged base, functionally important residues that participate in DNA binding and enzyme catalysis have been clearly identified and other residues, responsible for substrate specificity, have been inferred.

Original languageAmerican English
Pages (from-to)839-862
Number of pages24
JournalDNA Repair
Volume2
Issue number8
DOIs
StatePublished - 12 Aug 2003

Bibliographical note

Funding Information:
D.O.Z. acknowledges support from the Russian Foundation for Basic Research (02-04-49605) and Russian Ministry of Education (PD02-1.4-469). A.P.G. is supported by grants ES04068, CA47995 and CA17395 from the National Institutes of Health. The authors gratefully acknowledge the scientific contributions of their colleagues to the research described in this review, the editorial assistance of Annette Oestreicher and expert help from Erich Bremer in preparing the images and video of molecular models.

Keywords

  • 8-Oxoguanine
  • Crystal structure
  • DNA glycosylase
  • DNA repair
  • Formamidopyrimidine
  • Thymine glycol

Fingerprint

Dive into the research topics of 'Structural characterization of the Fpg family of DNA glycosylases'. Together they form a unique fingerprint.

Cite this