title: Structural characterization of the Fpg family of DNA glycosylases.
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.
authors.affiliation: Novosibirsk Institute of Bioorganic Chemistry, Siberian Division of Russian Academy of Sciences, 630090 Novosibirsk, Russia.
authors.forename: Dmitry O
authors.initials: DO
authors.lastname: Zharkov
authors.forename: Gil
authors.initials: G
authors.lastname: Shoham
authors.forename: Arthur P
authors.initials: AP
authors.lastname: Grollman
mesh_terms: D000595:Amino Acid Sequence; D004260:DNA Repair / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000378:metabolism; D043382:DNA-Formamidopyrimidine Glycosylase / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D043224:Deoxyribonuclease (Pyrimidine Dimer) / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D008957:Models, Genetic; D008969:Molecular Sequence Data; D016415:Sequence Alignment; D013379:Substrate Specificity / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; D043224:Deoxyribonuclease (Pyrimidine Dimer); D043382:DNA-Formamidopyrimidine Glycosylase