Linked Life Data

7947770

Source:http://linkedlifedata.com/resource/pubmed/id/7947770

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
46
pubmed:dateCreated
1994-12-21
pubmed:abstractText
One- and two-dimensional NMR spectroscopy and energy minimization calculations were used to investigate the conformation of a 2-aminofluorene- (AF-) modified model human c-H-ras1 protooncogene codon 61 deoxyoligonucleotide duplex, d(C1-A2-C3-C4-A5- [AF-G6]-G7-A8-A9-C10).-d(G11-T12-T13-C14-C15-T16 -G17-G18-T19-G20), in which the AF adduct is located at the third base of codon 61 with cytosine as the complementary nucleotide. Two interchangeable conformations of the AF-modified duplex, referred to as the external-AF conformation and the inserted-AF conformation, were determined from the NMR data. An analysis of the coalescence of resonances led to the estimation that the chemical exchange lifetime is greater than 3 ms but less than 20 ms at 30 degrees C, pH 7. In the external-AF conformation, Watson-Crick base-pair formation is observed for all 10 complementary nucleotides, including the AF-G6.C15 base pair. In the inserted-AF conformation, 9 of the 10 complementary bases form Watson-Crick base pairs; the AF-G6 imino proton exhibits no evidence of hydrogen bond formation with its complementary cytosine. Several NOEs between aminofluorene protons and DNA protons show that the AF moiety in the inserted-AF conformation stacks between the adjacent A5.T16 and G7.C14 base pairs. Solvated energy minimization calculations using distance restraints obtained from NOESY data at 2 degrees C with a 100-ms mixing time were performed to obtain representative structures of the external-AF and inserted-AF conformations. The external-AF conformer has the AF moiety protruding out of the major groove of a relatively unperturbed DNA duplex, leaving intact Watson-Crick base pairing for the AF-G6.C15 bases. Thus, the external-AF conformer may represent a visualization of a conformation that allows faithful replication. The inserted-AF conformer has the AF moiety stacked within the DNA helix, breaking the Watson-Crick base pairing of the modified guanine and its complementary cytosine and displacing the guanine and cytosine into the grooves. We label the inserted-AF conformer as a premutagenic conformation to reflect the displacement of the modified guanine. Interconversion between the structurally distinct external-AF and inserted-AF conformers takes place on a time scale of the same order as DNA replication. We have labeled this interconversion as a mutagenic switch to highlight a possible conformational equilibrium that may be important in replication.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0006-2960
pubmed:author
pubmed:issnType
Print
pubmed:day
22
pubmed:volume
33
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
13611-24
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1994
pubmed:articleTitle
Structural characterization of two interchangeable conformations of a 2-aminofluorene-modified DNA oligomer by NMR and energy minimization.
pubmed:affiliation
Department of Chemistry, University of Rochester, New York 14627.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.