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== | ==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== | ||
<StructureSection load='1y9h' size='340' side='right'caption='[[1y9h | <StructureSection load='1y9h' size='340' side='right'caption='[[1y9h]]' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[1y9h]] is a 2 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Y9H OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1Y9H FirstGlance]. <br> | <table><tr><td colspan='2'>[[1y9h]] is a 2 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Y9H OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1Y9H FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr> | ||
<tr id=' | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1y9h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1y9h OCA], [https://pdbe.org/1y9h PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1y9h RCSB], [https://www.ebi.ac.uk/pdbsum/1y9h PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1y9h ProSAT]</span></td></tr> | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1y9h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1y9h OCA], [https://pdbe.org/1y9h PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1y9h RCSB], [https://www.ebi.ac.uk/pdbsum/1y9h PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1y9h ProSAT]</span></td></tr> | ||
</table> | </table> | ||
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</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Amin | [[Category: Amin S]] | ||
[[Category: Broyde | [[Category: Broyde S]] | ||
[[Category: Geacintov | [[Category: Geacintov NE]] | ||
[[Category: Hingerty | [[Category: Hingerty BE]] | ||
[[Category: Huang | [[Category: Huang X]] | ||
[[Category: Kolbanovskiy | [[Category: Kolbanovskiy A]] | ||
[[Category: Lin | [[Category: Lin C]] | ||
[[Category: Patel | [[Category: Patel DJ]] | ||
[[Category: Zhang | [[Category: Zhang N]] | ||
Latest revision as of 12:30, 6 December 2023
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 displacementMethylation 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
Structural highlights
Publication Abstract from PubMedIt 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. 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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