1qsx

SOLUTION NMR STRUCTURE OF THE 2:1 HOECHST 33258-D(CTTTTGCAAAAG)2 COMPLEX

spinqualitylabelsall models 1qsx, 1 NMR models Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 1qsx is a 2 chain structure. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: HT, NA Resources: FirstGlance, OCA, RCSB, PDBsum Publication Abstract from PubMed The solution structure of the dodecamer duplex d(CTTTTGCAAAAG)(2)and its 2:1 complex with the bis -benzimidazole Hoechst 33258 has been investigated by NMR and NOE-restrained molecular dynamics (rMD) simulations. Drug molecules are bound in each of the two A-tracts with the bulky N-methylpiperazine ring of each drug located close to the central TG (CA) step, binding essentially to the narrow minor groove of each A-tract. MD simulations over 1 ns, using an explicit solvation model, reveal time-averaged sequence-dependent narrowing of the minor groove from the 3'-end towards the 5'-end of each TTTT sequence. Distinct junctions at the TpG (CpA) steps, characterised by large positive roll, low helical and propeller twists and rapid AT base pair opening rates, add to the widening of the groove at these sites and appear to account for the bound orientation of the two drug molecules with the N-methylpiperazine ring binding in the wider part of the groove close to the junctions. Comparisons between the free DNA structure and the 2:1 complex (heavy atom RMSD 1.55 A) reveal that these sequence-dependent features persist in both structures. NMR studies of the sequence d(GAAAAGCTTTTC)(2), in which the A-tracts have been inverted with the elimination of the TpG junctions, results in loss of orientational specificity of Hoechst 33258 and formation of multiple bound species in solution, consistent with the drug binding in a number of different orientations. Sequence-dependent variation in DNA minor groove width dictates orientational preference of Hoechst 33258 in A-tract recognition: solution NMR structure of the 2:1 complex with d(CTTTTGCAAAAG)(2).,Gavathiotis E, Sharman GJ, Searle MS Nucleic Acids Res. 2000 Feb 1;28(3):728-35. PMID:10637324 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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