Linked Life Data

11148051

Source:http://linkedlifedata.com/resource/pubmed/id/11148051

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2001-1-23
pubmed:abstractText
DNA glycosylase and glycosylase/abasic (AP) lyases are the enzymes responsible for initiating the base excision repair pathway by recognizing the damaged target base and catalyzing the breakage of the base-sugar glycosyl bond. The subset of glycosylases that have an associated AP lyase activity also catalyze DNA strand breakage at the resulting or preexisting AP site via a beta-elimination reaction, proceeding from an enzyme-DNA imino intermediate. Two distinct mechanisms have been proposed for the formation of this intermediate. These mechanisms essentially differ in the nature of the first bond broken and the timing of the opening of the deoxyribose ring. The data presented here demonstrate that the combined rate of sugar ring opening and reduction of the sugar is significantly slower than the rate of formation of a T4-pyrimidine dimer glycosylase (T4-pdg)-DNA intermediate. Using a methyl-deoxyribofuranose AP-site analogue that is incapable of undergoing sugar ring opening, it was demonstrated that the T4-pdg reaction can initiate at the ring-closed form, albeit at a drastically reduced rate. T4-pdg preferentially cleaved the beta-anomer of the methyl-deoxyribofuranose AP site analogue. This is consistent with a mechanism in which the methoxy group is backside-displaced by the amino group from the alpha-face of the deoxyribofuranose ring. In addition, studies examining rates of sugar-aldehyde reduction and the sodium borohydride concentration dependence of the rate of formation of the covalent imine intermediate suggest that the reduction of the intermediate is rate-limiting in the reaction.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Borohydrides, http://linkedlifedata.com/resource/pubmed/chemical/Carbon-Oxygen Lyases, http://linkedlifedata.com/resource/pubmed/chemical/DNA Glycosylases, http://linkedlifedata.com/resource/pubmed/chemical/DNA-(Apurinic or Apyrimidinic..., http://linkedlifedata.com/resource/pubmed/chemical/Deoxyribonuclease IV (Phage..., http://linkedlifedata.com/resource/pubmed/chemical/Deoxyribonucleosides, http://linkedlifedata.com/resource/pubmed/chemical/Macromolecular Substances, http://linkedlifedata.com/resource/pubmed/chemical/N-Glycosyl Hydrolases, http://linkedlifedata.com/resource/pubmed/chemical/Oligodeoxyribonucleotides, http://linkedlifedata.com/resource/pubmed/chemical/Schiff Bases, http://linkedlifedata.com/resource/pubmed/chemical/Thionucleotides, http://linkedlifedata.com/resource/pubmed/chemical/deoxyribopyrimidine endonucleosidase, http://linkedlifedata.com/resource/pubmed/chemical/sodium borohydride
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0006-2960
pubmed:author
pubmed:issnType
Print
pubmed:day
16
pubmed:volume
40
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
561-8
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2001
pubmed:articleTitle
The reaction mechanism of DNA glycosylase/AP lyases at abasic sites.
pubmed:affiliation
Center for Molecular Science and Department of Human Biological Chemistry and Genetics, University of Texas Medical Branch, Galveston, Texas 77555-1071, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't