title: Crystal structures of two archaeal 8-oxoguanine DNA glycosylases provide structural insight into guanine/8-oxoguanine distinction.
abstract: Among the four DNA bases, guanine is particularly vulnerable to oxidative damage and the most common oxidative product, 7,8-dihydro-8-oxoguanine (8-oxoG), is the most prevalent lesion observed in DNA molecules. Fortunately, 8-oxoG is recognized and excised by the 8-oxoguanine DNA glycosylase (Ogg) of the base excision repair pathway. Ogg enzymes are divided into three separate families, namely, Ogg1, Ogg2, and archaeal GO glycosylase (AGOG). To date, structures of members of both Ogg1 and AGOG families are known but no structural information is available for members of Ogg2. Here we describe the first crystal structures of two archaeal Ogg2: Methanocaldococcus janischii Ogg and Sulfolobus solfataricus Ogg. A structural comparison with OGG1 and AGOG suggested that the C-terminal lysine of Ogg2 may play a key role in discriminating between guanine and 8-oxoG. This prediction was substantiated by measuring the glycosylase/lyase activity of a C-terminal deletion mutant of MjaOgg.
authors.affiliation: Department of Microbiology and Molecular Genetics, The Markey Center for Molecular Genetics, University of Vermont, Stafford Hall, Burlington, VT 05405-0068, USA.
authors.forename: Frédérick
authors.initials: F
authors.lastname: Faucher
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Duclos
authors.forename: Viswanath
authors.initials: V
authors.lastname: Bandaru
authors.forename: Susan S
authors.initials: SS
authors.lastname: Wallace
authors.forename: Sylvie
authors.initials: S
authors.lastname: Doublié
mesh_terms: D000595:Amino Acid Sequence; D001059:Apoproteins / Q000737:chemistry / Q000378:metabolism; D019843:Archaeal Proteins / Q000737:chemistry* / Q000378:metabolism; D045647:DNA Glycosylases / Q000737:chemistry* / Q000378:metabolism; D006147:Guanine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D017015:Methanococcales / Q000201:enzymology / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D048229:Sulfolobus solfataricus / Q000201:enzymology / Q000378:metabolism
chemical_list: D001059:Apoproteins; D019843:Archaeal Proteins; C024829:8-hydroxyguanine; D006147:Guanine; D045647:DNA Glycosylases