1pg9
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(New page: 200px<br /><applet load="1pg9" size="450" color="white" frame="true" align="right" spinBox="true" caption="1pg9" /> '''NMR Solution Structure of an Oxaliplatin 1,2...)
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Revision as of 00:20, 25 November 2007
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NMR Solution Structure of an Oxaliplatin 1,2-d(GG) Intrastrand Cross-Link in a DNA Dodecamer Duplex
Overview
We have determined, at high resolution, the NMR solution structure of an, oxaliplatin-GG DNA dodecamer in the AGGC sequence context by 2D NMR, studies. Homonuclear assignment strategies resulted in unambiguous, assignment of 203 out of 249 protons, which corresponds to assignment of, approximately 81% of the protons. Assignments of H5' and H5" protons were, tentative due to resonance overlap. The structure of the oxaliplatin, duplex was calculated using the program CNS with a simulated annealing, protocol. A total of 510 experimental restraints were employed in the, structure calculation. Of 20 calculated structures, the 15 with the lowest, energy were accepted as a family. The RMSD of the 15 lowest energy, structures was 0.68 A, indicating good structural convergence. The, theoretical NOESY spectrum obtained by back-calculation from the final, average structure showed excellent agreement with the experimental data, indicating that the final structure was in good agreement with the, experimental NMR data. Significant conformational differences were, observed between the oxaliplatin-GG 12-mer DNA we studied and all previous, solution structures of cisplatin-GG DNA duplexes. For example, the, oxaliplatin-GG adduct shows much less distortion at the AG base-pair step, than the cisplatin-GG adducts. In addition, the oxaliplatin-GG structure, also has a narrow minor groove and an overall axis bend of about 31, degrees, both of which are very different from the recent NMR structures, for the cisplatin-GG adducts. These structural differences may explain, some of the biological differences between oxaliplatin- and cisplatin-GG, adducts.
About this Structure
1PG9 is a Protein complex structure of sequences from [1] with 1PT as ligand. Full crystallographic information is available from OCA.
Reference
NMR solution structure of an oxaliplatin 1,2-d(GG) intrastrand cross-link in a DNA dodecamer duplex., Wu Y, Pradhan P, Havener J, Boysen G, Swenberg JA, Campbell SL, Chaney SG, J Mol Biol. 2004 Aug 27;341(5):1251-69. PMID:15321720
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