| pubmed-article:11087352 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:11087352 | lifeskim:mentions | umls-concept:C0205103 | lld:lifeskim |
| pubmed-article:11087352 | lifeskim:mentions | umls-concept:C0003075 | lld:lifeskim |
| pubmed-article:11087352 | lifeskim:mentions | umls-concept:C0022262 | lld:lifeskim |
| pubmed-article:11087352 | lifeskim:mentions | umls-concept:C0077845 | lld:lifeskim |
| pubmed-article:11087352 | lifeskim:mentions | umls-concept:C0443286 | lld:lifeskim |
| pubmed-article:11087352 | lifeskim:mentions | umls-concept:C1280500 | lld:lifeskim |
| pubmed-article:11087352 | lifeskim:mentions | umls-concept:C2603343 | lld:lifeskim |
| pubmed-article:11087352 | lifeskim:mentions | umls-concept:C0332120 | lld:lifeskim |
| pubmed-article:11087352 | pubmed:issue | 46 | lld:pubmed |
| pubmed-article:11087352 | pubmed:dateCreated | 2000-12-12 | lld:pubmed |
| pubmed-article:11087352 | pubmed:abstractText | The DNA repair enzyme uracil DNA glycosylase catalyzes the first step in the uracil base excision repair pathway, the hydrolytic cleavage of the N-glycosidic bond of deoxyuridine in DNA. Here we report kinetic isotope effect (KIE) measurements that have allowed the determination of the transition-state structure for this important reaction. The small primary (13)C KIE (=1.010 +/- 0.009) and the large secondary alpha-deuterium KIE (=1.201 +/- 0.021) indicate that (i) the glycosidic bond is essentially completely broken in the transition state and (ii) there is significant sp(2) character at the anomeric carbon. Large secondary beta-deuterium KIEs were observed when [2'R-(2)H] = 1.102 +/- 0.011 and [2'S-(2)H] = 1.106 +/- 0.010. The nearly equal and large magnitudes of the two stereospecific beta-deuterium KIEs indicate strong hyperconjugation between the elongated glycosidic bond and both of the C2'-H2' bonds. Geometric interpretation of these beta-deuterium KIEs indicates that the furanose ring adopts a mild 3'-exo sugar pucker in the transition state, as would be expected for maximal stabilization of an oxocarbenium ion. Taken together, these results strongly indicate that the reaction proceeds through a dissociative transition state, with complete dissociation of the uracil anion followed by addition of water. To our knowledge, this is the first transition-state structure determined for enzymatic cleavage of the glycosidic linkage in a pyrimidine deoxyribonucleotide. | lld:pubmed |
| pubmed-article:11087352 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11087352 | pubmed:language | eng | lld:pubmed |
| pubmed-article:11087352 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11087352 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:11087352 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11087352 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11087352 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11087352 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11087352 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11087352 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11087352 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11087352 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11087352 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11087352 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11087352 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:11087352 | pubmed:month | Nov | lld:pubmed |
| pubmed-article:11087352 | pubmed:issn | 0006-2960 | lld:pubmed |
| pubmed-article:11087352 | pubmed:author | pubmed-author:WernerR MRM | lld:pubmed |
| pubmed-article:11087352 | pubmed:author | pubmed-author:StiversJ TJT | lld:pubmed |
| pubmed-article:11087352 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:11087352 | pubmed:day | 21 | lld:pubmed |
| pubmed-article:11087352 | pubmed:volume | 39 | lld:pubmed |
| pubmed-article:11087352 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:11087352 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:11087352 | pubmed:pagination | 14054-64 | lld:pubmed |
| pubmed-article:11087352 | pubmed:dateRevised | 2008-11-21 | lld:pubmed |
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| pubmed-article:11087352 | pubmed:meshHeading | pubmed-meshheading:11087352... | lld:pubmed |
| pubmed-article:11087352 | pubmed:meshHeading | pubmed-meshheading:11087352... | lld:pubmed |
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| pubmed-article:11087352 | pubmed:meshHeading | pubmed-meshheading:11087352... | lld:pubmed |
| pubmed-article:11087352 | pubmed:year | 2000 | lld:pubmed |
| pubmed-article:11087352 | pubmed:articleTitle | Kinetic isotope effect studies of the reaction catalyzed by uracil DNA glycosylase: evidence for an oxocarbenium ion-uracil anion intermediate. | lld:pubmed |
| pubmed-article:11087352 | pubmed:affiliation | Center for Advanced Research in Biotechnology of the University of Maryland Biotechnology Institutes and National Institute of Standards and Technology, 9600 Gudelsky Drive, Rockville, Maryland 20850, USA. | lld:pubmed |
| pubmed-article:11087352 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:11087352 | pubmed:publicationType | Research Support, U.S. Gov't, P.H.S. | lld:pubmed |
| pubmed-article:11087352 | pubmed:publicationType | Research Support, U.S. Gov't, Non-P.H.S. | lld:pubmed |
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