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 language | English |
|---|---|
| Pages (from-to) | 839-862 |
| Number of pages | 24 |
| Journal | DNA Repair |
| Volume | 2 |
| Issue number | 8 |
| DOIs | |
| State | Published - 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