1QSX

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

1QSX の概要

• エントリーDOI: 10.2210/pdb1qsx/pdb
• 分子名称: 5'-D(CP*TP*TP*TP*TP*GP*CP*AP*AP*AP*AP*G)-3', SODIUM ION, 2'-(4-HYDROXYPHENYL)-5-(4-METHYL-1-PIPERAZINYL)-2,5'-BI-BENZIMIDAZOLE (3 entities in total)
• 機能のキーワード: drug-dna complex, hoechst 33258, deoxyribonucleic acid, minor groove recognition, double helix, nmr spectroscopy, dna
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 8608.64

構造登録者

Gavathiotis, E.,Sharman, G.J.,Searle, M.S. (登録日: 1999-06-24, 公開日: 2000-02-07, 最終更新日: 2024-05-22)

主引用文献

Gavathiotis, E.,Sharman, G.J.,Searle, M.S.
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).
Nucleic Acids Res., 28:728-735, 2000

PubMed Abstract: 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.

PubMed: 10637324
DOI: 10.1093/nar/28.3.728

実験手法

SOLUTION NMR