Structural characterization of Clostridium acetobutylicum 8-oxoguanine DNA glycosylase in its apo form and in complex with 8-oxodeoxyguanosine.
J Mol Biol
; 387(3): 669-79, 2009 Apr 03.
Article
em En
| MEDLINE
| ID: mdl-19361427
ABSTRACT
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-oxoGC), but it can also form a stable Hoogsteen pair with adenine (8-oxoGA), leading to a GC-->TA 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.
Texto completo:
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Bases de dados:
MEDLINE
Assunto principal:
Proteínas de Bactérias
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Estrutura Terciária de Proteína
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DNA Glicosilases
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Clostridium acetobutylicum
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Desoxiguanosina
Limite:
Humans
Idioma:
En
Revista:
J Mol Biol
Ano de publicação:
2009
Tipo de documento:
Article
País de afiliação:
Estados Unidos