1y9h: Difference between revisions
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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''' | {{Structure | ||
|PDB= 1y9h |SIZE=350|CAPTION= <scene name='initialview01'>1y9h</scene> | |||
|SITE= | |||
|LIGAND= <scene name='pdbligand=BAP:1,2,3-TRIHYDROXY-1,2,3,4-TETRAHYDROBENZO[A]PYRENE'>BAP</scene> | |||
|ACTIVITY= | |||
|GENE= | |||
}} | |||
'''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''' | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
1Y9H is a [ | 1Y9H is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/ ]. 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:// | 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: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Amin, S.]] | [[Category: Amin, S.]] | ||
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[[Category: p53 mutation hot spot]] | [[Category: p53 mutation hot spot]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 15:20:02 2008'' | ||
Revision as of 16:20, 20 March 2008
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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
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
1Y9H is a Protein complex structure of sequences from [1]. 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 [[Category: benzo[a]pyrene]]
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