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Crystal structures of MBOgg1 in complex with two abasic DNA ligands

DOI: 10.1016/j.jsb.2012.12.003 DOI Help

Authors: Hongjun Yu (of Biophysics, Chinese Academy of Sciences) , Mingzhang Yang (of Biophysics, Chinese Academy of Sciences) , Xian-en Zhang (Institute of Biophysics, Chinese Academy of Sciences) , Lijun Bi (Institute of Biophysics, Chinese Academy of Sciences) , Tao Jiang (Institute of Biophysics,CAS)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Journal Of Structural Biology , VOL 181 (3)

State: Published (Approved)
Published: December 2012

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/DNATHF:C) or thymine (MBOgg1/DNATHF:T). Different states of THF (extrahelical or intrahelical) are observed in the two complexes of the ASU of MBOgg1/DNATHF: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/DNATHF:T with MBOgg1/DNATHF: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.

Journal Keywords: 8-Oxoguanine Glycosylase; Estranged Base Recognition; Single Turnover Kinetics; Abasic Site; Crystal Structure

Subject Areas: Biology and Bio-materials


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