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==Structure of the trimethylene N2-dG:N2-dG interstrand cross-link in 5'-CpG-3' sequence context==
<StructureSection load='2knk' size='340' side='right'caption='[[2knk]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2knk]] is a 2 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2KNK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2KNK FirstGlance]. <br>
</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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=TME:PROPANE'>TME</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=2knk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2knk OCA], [https://pdbe.org/2knk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2knk RCSB], [https://www.ebi.ac.uk/pdbsum/2knk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2knk ProSAT]</span></td></tr>
</table>
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== Publication Abstract from PubMed ==
Synthetically derived trimethylene interstrand DNA cross-links have been used as surrogates for the native cross-links that arise from the 1,N(2)-deoxyguanosine adducts derived from alpha,beta-unsaturated aldehydes. The native enal-mediated cross-linking occurs in the 5'-CpG-3' sequence context but not in the 5'-GpC-3' sequence context. The ability of the native enal-derived 1,N(2)-dG adducts to induce interstrand DNA cross-links in the 5'-CpG-3' sequence as opposed to the 5'-GpC-3' sequence is attributed to the destabilization of the DNA duplex in the latter sequence context. Here, we report higher accuracy solution structures of the synthetically derived trimethylene cross-links, which are refined from NMR data with the AMBER force field. When the synthetic trimethylene cross-links are placed into either the 5'-CpG-3' or the 5'-GpC-3' sequence contexts, the DNA duplex maintains B-DNA geometry with structural perturbations confined to the cross-linked base pairs. Watson-Crick hydrogen bonding is conserved throughout the duplexes. Although different from canonical B-DNA stacking, the cross-linked and the neighbor base pairs stack in the 5'-CpG-3' sequence. In contrast, the stacking at the cross-linked base pairs in the 5'-GpC-3' sequence is greatly perturbed. The pi-stacking interactions between the cross-linked and the neighbor base pairs are reduced. This is consistent with remarkable chemical shift perturbations of the C(5) H5 and H6 nucleobase protons that shifted downfield by 0.4-0.5 ppm. In contrast, these chemical shift perturbations in the 5'-CpG-3' sequence are not remarkable, consistent with the stacked structure. The differential stacking of the base pairs at the cross-linking region probably explains the difference in stabilities of the trimethylene cross-links in the 5'-CpG-3' and 5'-GpC-3' sequence contexts and might, in turn, account for the sequence selectivity of the interstrand cross-link formation induced by the native enal-derived 1,N(2)-dG adducts.

Differential base stacking interactions induced by trimethylene interstrand DNA cross-links in the 5'-CpG-3' and 5'-GpC-3' sequence contexts.,Huang H, Dooley PA, Harris CM, Harris TM, Stone MP Chem Res Toxicol. 2009 Nov;22(11):1810-6. PMID:19916525<ref>PMID:19916525</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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== References ==
<references/>
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</StructureSection>
[[Category: Large Structures]]
[[Category: Dooley PA]]
[[Category: Harris CM]]
[[Category: Harris TM]]
[[Category: Huang H]]
[[Category: Stone MP]]