Structural characterization of Clostridium acetobutylicum 8-oxoguanine DNA glycosylase in its apo form and in complex with 8-oxodeoxyguanosine.
DNA is subject to a multitude of oxidative damages generated by oxidizing agents from metabolism and exogenous sources and by ionizing radiation. Guanine is particularly vulnerable to oxidation, and the most common oxidative product 8-oxoguanine (8-oxoG) is the most prevalent lesion observed in DNA molecules. 8-OxoG can form a normal Watson-Crick pair with cytosine (8-oxoG:C), but it can also form a stable Hoogsteen pair with adenine (8-oxoG:A), leading to a G:C-->T:A transversion after replication. Fortunately, 8-oxoG is recognized and excised by either of two DNA glycosylases of the base excision repair pathway: formamidopyrimidine-DNA glycosylase and 8-oxoguanine DNA glycosylase (Ogg). While Clostridium acetobutylicum Ogg (CacOgg) DNA glycosylase can specifically recognize and remove 8-oxoG, it displays little preference for the base opposite the lesion, which is unusual for a member of the Ogg1 family. This work describes the crystal structures of CacOgg in its apo form and in complex with 8-oxo-2'-deoxyguanosine. A structural comparison between the apo form and the liganded form of the enzyme reveals a structural reorganization of the C-terminal domain upon binding of 8-oxoG, similar to that reported for human OGG1. A structural comparison of CacOgg with human OGG1, in complex with 8-oxoG containing DNA, provides a structural rationale for the lack of opposite base specificity displayed by CacOgg.
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.
Frédérick
F
Faucher
Susan M
SM
Robey-Bond
Susan S
SS
Wallace
Sylvie
S
Doublié
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D001665:Binding Sites; D046969:Clostridium acetobutylicum / Q000201:enzymology* / Q000235:genetics; D003460:Crystallization; D045647:DNA Glycosylases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D004260:DNA Repair; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D014961:X-Ray Diffraction
D001426:Bacterial Proteins; D000080242:8-Hydroxy-2'-Deoxyguanosine; D045647:DNA Glycosylases; C479058:oxoguanine glycosylase 1, human; D003849:Deoxyguanosine