2knk | pdb_00002knk

Structure of the trimethylene N2-dG:N2-dG interstrand cross-link in 5'-CpG-3' sequence context

spinqualitylabelsall models 2knk, 1 NMR models Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2knk is a 2 chain structure. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: TME Related: 1hz2, 2knl Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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