Linked Life Data

12206669

Source:http://linkedlifedata.com/resource/pubmed/id/12206669

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
36
pubmed:dateCreated
2002-9-3
pubmed:abstractText
Uracil DNA glycosylase (UDG) is a base excision repair enzyme that specifically recognizes and removes uracil from double- or single-stranded DNA. The efficiency of the enzyme depends on the DNA sequence surrounding the uracil. Crystal structures of UDG in complex with DNA reveal that the DNA is severely bent and distorted in the region of the uracil. This suggests that the sequence-dependent efficiency of the enzyme may be related to the energetic cost of DNA distortion in the process of specific damage recognition. To test this hypothesis, molecular dynamics simulations were performed on two sequences representing extreme cases of UDG efficiency, AUA/TAT (high efficiency) and GUG/CAC (low efficiency). Analysis of the simulations shows that the effective bending force constants are lower for the AUA/TAT sequence, indicating that this sequence is more flexible than the GUG/CAC sequence. Fluorescence lifetimes of the adenine analogue 2-aminopurine (2AP), replacing adenine opposite the uracil, are shorter in the context of the AUA/TAT sequence, indicating more dynamic base-base interaction and greater local flexibility than in the GUG/CAC sequence. Furthermore, the K(M) of Escherichia coli UDG for the AUA/TAT sequence is 10-fold smaller than that for the GUG/CAC sequence, while the k(cat) is only 2-fold smaller. This indicates that differences in UDG efficiency largely arise from differences in binding and not catalysis. These results link directly flexibility near the damaged DNA site with the efficiency of DNA repair.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0006-2960
pubmed:author
pubmed:issnType
Print
pubmed:day
10
pubmed:volume
41
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
10976-84
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
Role of DNA flexibility in sequence-dependent activity of uracil DNA glycosylase.
pubmed:affiliation
Department of Pharmacology and Biological Chemistry, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, New York 10029, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.