title: Crystal structures of MBOgg1 in complex with two abasic DNA ligands.
abstract: 7,8-Dihydro-8-oxoguanine (8-oxoG) is one of the most common oxidative DNA lesions. 8-oxoguanine DNA glycosylases (Oggs) detect and excise 8-oxoG through a multiple-step process. To better understand the basis for estranged base recognition, we have solved the crystal structures of MBOgg1, the 8-oxoguanine DNA glycosylase of Thermoanaerobacter tengcongensis, in complex with DNA containing a tetrahydrofuranyl site (THF, a stable abasic site analog) paired with an estranged cytosine (MBOgg1/DNA(THF:C)) or thymine (MBOgg1/DNA(THF:T)). Different states of THF (extrahelical or intrahelical) are observed in the two complexes of the ASU of MBOgg1/DNA(THF:C) structure. Analyses of their different interaction modes reveal that variable contacts on the 5' region flanking the THF abasic site are correlated with the states of the THF. Comparison of MBOgg1/DNA(THF:T) with MBOgg1/DNA(THF:C) indicates that the non-preferred estranged T may affect MBOgg1's contacts with the 5' flank of the lesion strand. Furthermore, we identified a region in MBOgg1 that is rich in positive charges and interacts with the 5' region flanking the lesion. This region is conserved only in non-eukaryotic Oggs, and additional mutagenesis and biochemical assays reveal that it may contribute to the distinct estranged base specificities between eukaryotic and non-eukaryotic Oggs.
authors.affiliation: National Key Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Chaoyang District, Beijing 100101, China.
authors.forename: Hongjun
authors.initials: H
authors.lastname: Yu
authors.forename: Mingzhang
authors.initials: M
authors.lastname: Yang
authors.forename: Xian-en
authors.initials: XE
authors.lastname: Zhang
authors.forename: Lijun
authors.initials: L
authors.lastname: Bi
authors.forename: Tao
authors.initials: T
authors.lastname: Jiang
mesh_terms: D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry* / Q000378:metabolism*; D045647:DNA Glycosylases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D020349:Surface Plasmon Resonance; D046968:Thermoanaerobacter / Q000201:enzymology
chemical_list: D004247:DNA; D045647:DNA Glycosylases