Structural Characterization of Clostridium acetobutylicum 8-Oxoguanine DNA Glycosylase in Its Apo Form and in Complex with 8-Oxodeoxyguanosine

Journal Article · Tue Jun 30 04:00:00 EDT 2009 · J. Mol. Biol.

DOI:https://doi.org/10.1016/j.jmb.2009.01.067· OSTI ID:1005697

Faucher, Frédérick; Robey-Bond, Susan M; Wallace, Susan S; Doublié, Sylvie

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 {yields} 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.

• Research Organization: Argonne National Laboratory (ANL)
• Sponsoring Organization: USDOE
• OSTI ID: 1005697
• Journal Information: J. Mol. Biol., Journal Name: J. Mol. Biol. Journal Issue: (3) ; 04, 2009 Vol. 387; ISSN JMOBAK; ISSN 0022-2836
• Country of Publication: United States
• Language: ENGLISH

Related Subjects

36 MATERIALS SCIENCE
ADENINES
CLOSTRIDIUM ACETOBUTYLICUM
CRYSTAL STRUCTURE
CYTOSINE
DNA
DNA REPAIR
ENZYMES
EXCISION REPAIR
GUANINE
HUMAN POPULATIONS
IONIZING RADIATIONS
METABOLISM
MOLECULES
OXIDATION
OXIDIZERS
SPECIFICITY