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'''Methylation of cytosine at C5 in a CpG sequence context causes a conformational switch of a benzo[a]pyrene diol epoxide-N2-guanine adduct in DNA from a minor groove alignment to intercalation with base displacement''' | '''Methylation of cytosine at C5 in a CpG sequence context causes a conformational switch of a benzo[a]pyrene diol epoxide-N2-guanine adduct in DNA from a minor groove alignment to intercalation with base displacement''' | ||
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==About this Structure== | ==About this Structure== | ||
Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Y9H OCA]. | |||
==Reference== | ==Reference== | ||
Methylation of cytosine at C5 in a CpG sequence context causes a conformational switch of a benzo[a]pyrene diol epoxide-N2-guanine adduct in DNA from a minor groove alignment to intercalation with base displacement., Zhang N, Lin C, Huang X, Kolbanovskiy A, Hingerty BE, Amin S, Broyde S, Geacintov NE, Patel DJ, J Mol Biol. 2005 Mar 4;346(4):951-65. Epub 2004 Dec 31. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15701509 15701509] | Methylation of cytosine at C5 in a CpG sequence context causes a conformational switch of a benzo[a]pyrene diol epoxide-N2-guanine adduct in DNA from a minor groove alignment to intercalation with base displacement., Zhang N, Lin C, Huang X, Kolbanovskiy A, Hingerty BE, Amin S, Broyde S, Geacintov NE, Patel DJ, J Mol Biol. 2005 Mar 4;346(4):951-65. Epub 2004 Dec 31. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15701509 15701509] | ||
[[Category: Amin, S.]] | [[Category: Amin, S.]] | ||
[[Category: Broyde, S.]] | [[Category: Broyde, S.]] | ||
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[[Category: Patel, D J.]] | [[Category: Patel, D J.]] | ||
[[Category: Zhang, N.]] | [[Category: Zhang, N.]] | ||
[[Category: | [[Category: Bpde]] | ||
[[Category: Conformational switch]] | |||
[[Category: | [[Category: Cytosine methylation]] | ||
[[Category: | [[Category: Dna adduct]] | ||
[[Category: | [[Category: P53 mutation hot spot]] | ||
[[Category: | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 16:02:33 2008'' | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | |||
Revision as of 16:02, 3 May 2008
Methylation of cytosine at C5 in a CpG sequence context causes a conformational switch of a benzo[a]pyrene diol epoxide-N2-guanine adduct in DNA from a minor groove alignment to intercalation with base displacement
OverviewOverview
It is well known that CpG dinucleotide steps in DNA, which are highly methylated at the 5-position of cytosine (meC) in human tissues, exhibit a disproportionate number of mutations within certain codons of the p53 gene. There is ample published evidence indicating that the reactivity of guanine with anti-B[a]PDE (a metabolite of the environmental carcinogen benzo[a]pyrene) at CpG mutation hot spots is enhanced by the methylation of the cytosine residue flanking the target guanine residue on the 5'-side. In this work we demonstrate that such a methylation can also dramatically affect the conformational characteristics of an adduct derived from the reaction of one of the two enantiomers of anti-B[a]PDE with the exocyclic amino group of guanine ([BP]G adduct). A detailed NMR study indicates that the 10R (-)-trans-anti-[BP]G adduct undergoes a transition from a minor groove-binding alignment of the aromatic BP ring system in the unmethylated C-[BP]G sequence context, to an intercalative BP alignment with a concomitant displacement of the modified guanine residue into the minor groove in the methylated meC-[BP]G sequence context. By contrast, a minor groove-binding alignment was observed for the stereoisomeric 10S (+)-trans-anti-[BP]G adduct in both the C-[BP]G and meC-[BP]G sequence contexts. This remarkable conformational switch resulting from the presence of a single methyl group at the 5-position of the cytosine residue flanking the lesion on the 5'-side, is attributed to the hydrophobic effect of the methyl group that can stabilize intercalated adduct conformations in an adduct stereochemistry-dependent manner. Such conformational differences in methylated and unmethylated CpG sequences may be significant because of potential alterations in the cellular processing of the [BP]G adducts by DNA transcription, replication, and repair enzymes.
About this StructureAbout this Structure
Full crystallographic information is available from OCA.
ReferenceReference
Methylation of cytosine at C5 in a CpG sequence context causes a conformational switch of a benzo[a]pyrene diol epoxide-N2-guanine adduct in DNA from a minor groove alignment to intercalation with base displacement., Zhang N, Lin C, Huang X, Kolbanovskiy A, Hingerty BE, Amin S, Broyde S, Geacintov NE, Patel DJ, J Mol Biol. 2005 Mar 4;346(4):951-65. Epub 2004 Dec 31. PMID:15701509 Page seeded by OCA on Sat May 3 16:02:33 2008