1s9n
From Proteopedia
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Solution structure of the nitrous acid (G)-(G) cross-linked DNA dodecamer duplex GCATCC(G)GATGC
Overview
Nitrous acid is a mutagenic agent. It can induce interstrand cross-links, in duplex DNA, preferentially at d(CpG) steps: two guanines on opposite, strands are linked via a single shared exocyclic imino group. Recent, synthetic advances have led to the production of large quantities of such, structurally homogenous cross-linked duplex DNA. Here we present the high, resolution solution structure of the cross-linked dodecamer, [d(GCATCCGGATGC)]2 (the cross-linked guanines are underlined), determined, by 2D NMR spectroscopy, distance geometry, restrained molecular dynamics, and iterative NOE refinement. The cross-linked guanines form a nearly, planar covalently linked 'G:G base pair' with only minor propeller, twisting, while the cytidine bases of their normal base pairing partners, have been flipped out of the helix and adopt well defined extrahelical, positions in the minor groove. On the 5'-side of the cross-link, the minor, groove is widened to accommodate these extrahelical bases, and the major, groove becomes quite narrow at the cross-link. The cross-linked 'G:G base, pair' is well stacked on the spatially adjacent C:G base pairs, particularly on the 3'-side guanines. In addition to providing the first, structure of a nitrous acid cross-link in DNA, these studies could be of, major importance to the understanding of the mechanisms of nitrous acid, cross-linking and mutagenicity, as well as the mechanisms responsible for, its repair in intracellular environments. It is also the shortest DNA, cross-link structure to be described.
About this Structure
1S9N is a Protein complex structure of sequences from [1]. Full crystallographic information is available from OCA.
Reference
Solution structure of a nitrous acid induced DNA interstrand cross-link., Edfeldt NB, Harwood EA, Sigurdsson ST, Hopkins PB, Reid BR, Nucleic Acids Res. 2004 May 20;32(9):2785-94. Print 2004. PMID:15155847
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