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| ==AG(7-deaza)G FAPY modified duplex== | | ==AG(7-deaza)G FAPY modified duplex== |
| <StructureSection load='2mms' size='340' side='right' caption='[[2mms]], [[NMR_Ensembles_of_Models | 1 NMR models]]' scene=''> | | <StructureSection load='2mms' size='340' side='right'caption='[[2mms]]' scene=''> |
| == Structural highlights == | | == Structural highlights == |
| <table><tr><td colspan='2'>[[2mms]] is a 2 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2MMS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2MMS FirstGlance]. <br> | | <table><tr><td colspan='2'>[[2mms]] is a 2 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2MMS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2MMS FirstGlance]. <br> |
| </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=7GU:7-DEAZA-2-DEOXYGUANOSINE-5-MONOPHOSPHATE'>7GU</scene>, <scene name='pdbligand=FAG:[1,2-DIDEOXY[2-AMINO-5-([9-HYDROXY-AFLATOXINB2-8-YL]-FORMYL-AMINO)-6-OXO-1,6-IHYDRO-PYRIMIDIN-4-YLAMINO]-RIBOFURANOSE]-5-MONOPHOSPHATE+GROUP'>FAG</scene></td></tr> | | </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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2mms FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2mms OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2mms RCSB], [http://www.ebi.ac.uk/pdbsum/2mms PDBsum]</span></td></tr> | | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=7GU:7-DEAZA-2-DEOXYGUANOSINE-5-MONOPHOSPHATE'>7GU</scene>, <scene name='pdbligand=FAG:[1,2-DIDEOXY[2-AMINO-5-([9-HYDROXY-AFLATOXINB2-8-YL]-FORMYL-AMINO)-6-OXO-1,6-IHYDRO-PYRIMIDIN-4-YLAMINO]-RIBOFURANOSE]-5-MONOPHOSPHATE+GROUP'>FAG</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=2mms FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2mms OCA], [https://pdbe.org/2mms PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2mms RCSB], [https://www.ebi.ac.uk/pdbsum/2mms PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2mms ProSAT]</span></td></tr> |
| </table> | | </table> |
| <div style="background-color:#fffaf0;">
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| == Publication Abstract from PubMed ==
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| Aflatoxin B1 (AFB1), a mycotoxin produced by Aspergillus flavus, is oxidized by cytochrome P450 enzymes to aflatoxin B1-8,9-epoxide, which alkylates DNA at N7-dG. Under basic conditions, this N7-dG adduct rearranges to yield the trans-8,9-dihydro-8-(2,6-diamino-4-oxo-3,4-dihydropyrimid-5-yl-formamido)-9-hydro xy aflatoxin B1 (AFB1-FAPY) adduct. The AFB1-FAPY adduct exhibits geometrical isomerism involving the formamide moiety. NMR analyses of duplex oligodeoxynucleotides containing the 5'-XA-3', 5'-XC-3', 5'-XT-3', and 5'-XY-3' sequences (X = AFB1-FAPY; Y = 7-deaza-dG) demonstrate that the equilibrium between E and Z isomers is controlled by major groove hydrogen bonding interactions. Structural analysis of the adduct in the 5'-XA-3' sequence indicates the preference of the E isomer of the formamide group, attributed to formation of a hydrogen bond between the formyl oxygen and the N6 exocyclic amino group of the 3'-neighbor adenine. While the 5'-XA-3' sequence exhibits the E isomer, the 5'-XC-3' sequence exhibits a 7:3 E:Z ratio at equilibrium at 283 K. The E isomer is favored by a hydrogen bond between the formyl oxygen and the N4-dC exocyclic amino group of the 3'-neighbor cytosine. The 5'-XT-3' and 5'-XY-3' sequences cannot form such a hydrogen bond between the formyl oxygen and the 3'-neighbor T or Y, respectively, and in these sequence contexts the Z isomer is favored. Additional equilibria between alpha and beta anomers and the potential to exhibit atropisomers about the C5-N5 bond do not depend upon sequence. In each of the four DNA sequences, the AFB1-FAPY adduct maintains the beta deoxyribose configuration. Each of these four sequences feature the atropisomer of the AFB1 moiety that is intercalated above the 5'-face of the damaged guanine. This enforces the Ra axial conformation for the C5-N5 bond.
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| DNA Sequence Modulates Geometrical Isomerism of the trans-8,9-Dihydro-8-(2,6-diamino-4-oxo-3,4-dihydropyrimid-5-yl-formamido)-9-hydro xy Aflatoxin B Adduct.,Li L, Brown KL, Ma R, Stone MP Chem Res Toxicol. 2015 Jan 14. PMID:25587868<ref>PMID:25587868</ref>
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| From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| </div>
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| == References ==
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| <references/>
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| __TOC__ | | __TOC__ |
| </StructureSection> | | </StructureSection> |
| [[Category: Li, L]] | | [[Category: Large Structures]] |
| [[Category: Stone, M]] | | [[Category: Li L]] |
| [[Category: Aflatoxin b1]] | | [[Category: Stone M]] |
| [[Category: Deoxyribonucleic acid]]
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| [[Category: Dna]]
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| [[Category: Dna adduct]]
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| [[Category: Fapy]]
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| [[Category: Formamidopyrimidine]]
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| [[Category: Hydrogen bond]]
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| [[Category: Intercalation]]
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| [[Category: Sequence dependence]]
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