Linked Life Data

20640798

Source:http://linkedlifedata.com/resource/pubmed/id/20640798

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2010-7-19
pubmed:abstractText
E. coli AlkB is a DNA repair enzyme that catalyzes the de-methylation of DNA by means of a non-heme iron and alpha-keto glutarate as a co-factor. The proposed reaction mechanism can be separated in four stages. The first stage involves the binding of the co-factor and molecular oxygen to the Fe in the active site. This is followed by the formation of a ferryl intermediate in a high-spin state, along with CO(2) and succinate. Subsequently, the O atom on the Fe center is reoriented. The last stage comprises the oxidative de-methylation of the base to produce the native DNA base and formaldehyde. This stage also includes the rate limiting step in the reaction. Here, the last stage of the proposed reaction mechanism of AlkB has been studied for a model of the active site with DFT methods. Minimum structures have been calculated for all intermediates along the path in triplet and quintet spin states. Our results point to the quintet states as more stable, in agreement with previously reported calculations. Potential energy barriers have been obtained for all the steps along this last stage in the quintet state. In the first step the oxygen bound to the Fe center of the ferryl intermediate abstracts a hydrogen atom from the methyl moiety. This first step corresponds to the rate limiting step in the reaction. The calculated barrier for this step is 26.7 kcal/mol. The subsequent steps are highly exoergic. This energetic picture is in qualitative agreement with previously reported results. The calculated energy difference between the ferryl intermediate and the final product is -75.7 kcal/mol for a model with succinate in the active site and -49.3 kcal/mol for a model where the succinate is replaced by water. Our calculated mechanism is slightly different than the previously reported one. These results suggest the possibility of more than one mechanism. This is currently under investigation by ab initio QM/MM methods.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1913-2751
pubmed:author
pubmed:issnType
Print
pubmed:volume
2
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
70-7
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
DFT study of a model system for the dealkylation step catalyzed by AlkB.
pubmed:affiliation
Department of Chemistry, Wayne State University, Detroit, MI 48202, USA. andres@chem.wayne.edu
pubmed:publicationType
Journal Article