1y9h: Difference between revisions
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|PDB= 1y9h |SIZE=350|CAPTION= <scene name='initialview01'>1y9h</scene> | |PDB= 1y9h |SIZE=350|CAPTION= <scene name='initialview01'>1y9h</scene> | ||
|SITE= | |SITE= | ||
|LIGAND= <scene name='pdbligand=BAP:1,2,3-TRIHYDROXY-1,2,3,4-TETRAHYDROBENZO[A]PYRENE'>BAP</scene> | |LIGAND= <scene name='pdbligand=5CM:5-METHYL-2'-DEOXY-CYTIDINE-5'-MONOPHOSPHATE'>5CM</scene>, <scene name='pdbligand=BAP:1,2,3-TRIHYDROXY-1,2,3,4-TETRAHYDROBENZO[A]PYRENE'>BAP</scene>, <scene name='pdbligand=DA:2'-DEOXYADENOSINE-5'-MONOPHOSPHATE'>DA</scene>, <scene name='pdbligand=DC:2'-DEOXYCYTIDINE-5'-MONOPHOSPHATE'>DC</scene>, <scene name='pdbligand=DG:2'-DEOXYGUANOSINE-5'-MONOPHOSPHATE'>DG</scene>, <scene name='pdbligand=DT:THYMIDINE-5'-MONOPHOSPHATE'>DT</scene> | ||
|ACTIVITY= | |ACTIVITY= | ||
|GENE= | |GENE= | ||
|DOMAIN= | |||
|RELATEDENTRY= | |||
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1y9h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1y9h OCA], [http://www.ebi.ac.uk/pdbsum/1y9h PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1y9h RCSB]</span> | |||
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[[Category: Patel, D J.]] | [[Category: Patel, D J.]] | ||
[[Category: Zhang, N.]] | [[Category: Zhang, N.]] | ||
[[Category: benzo[a]pyrene]] | [[Category: benzo[a]pyrene]] | ||
[[Category: bpde]] | [[Category: bpde]] | ||
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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 | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 01:00:29 2008'' | ||
Revision as of 01:00, 31 March 2008
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| Ligands: | , , , , , | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
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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