title: The C-terminal lysine of Ogg2 DNA glycosylases is a major molecular determinant for guanine/8-oxoguanine distinction.
abstract: 7,8-Dihydro-8-oxoguanine (8-oxoG) is a major oxidative lesion found in DNA. The 8-oxoguanine DNA glycosylases (Ogg) responsible for the removal of 8-oxoG are divided into three families Ogg1, Ogg2 and AGOG. The Ogg2 members are devoid of the recognition loop used by Ogg1 to discriminate between 8-oxoG and guanine and it was unclear until recently how Ogg2 enzymes recognize the oxidized base. We present here the first crystallographic structure of an Ogg2 member, Methanocaldococcus janischii Ogg, in complex with a DNA duplex containing the 8-oxoG lesion. This structure highlights the crucial role of the C-terminal lysine, strictly conserved in Ogg2, in the recognition of 8-oxoG. The structure also reveals that Ogg2 undergoes a conformational change upon DNA binding similar to that observed in Ogg1 glycosylases. Furthermore, this work provides a structural rationale for the lack of opposite base specificity in this family of enzymes.
authors.affiliation: Department of Microbiology and Molecular Genetics, The Markey Center for Molecular Genetics, University of Vermont, Stafford Hall, 95 Carrigan Drive, Burlington, VT 05405-0068, USA.
authors.forename: Frédérick
authors.initials: F
authors.lastname: Faucher
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*; D001665:Binding Sites; D018360:Crystallography, X-Ray; D003596:Cytosine / Q000378:metabolism; D045647:DNA Glycosylases / Q000737:chemistry; D019641:DNA, Archaeal / Q000737:chemistry / Q000378:metabolism; D006147:Guanine / Q000031:analogs & derivatives* / Q000378:metabolism; D006801:Humans; D007477:Ions; D008239:Lysine / Q000378:metabolism*; D017015:Methanococcales / Q000201:enzymology*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D017433:Protein Structure, Secondary; D016415:Sequence Alignment; D012964:Sodium / Q000378:metabolism; D055672:Static Electricity; D013329:Structure-Activity Relationship
chemical_list: D001059:Apoproteins; D019843:Archaeal Proteins; D019641:DNA, Archaeal; D007477:Ions; C024829:8-hydroxyguanine; D006147:Guanine; D003596:Cytosine; D012964:Sodium; D045647:DNA Glycosylases; C479058:oxoguanine glycosylase 1, human; D008239:Lysine