1PQQ

NMR Structure of a Cyclic Polyamide-DNA Complex

1PQQ の概要

• エントリーDOI: 10.2210/pdb1pqq/pdb
• NMR情報: BMRB: 5927
• 分子名称: 5'-D(*CP*GP*CP*TP*AP*AP*CP*AP*GP*GP*C)-3', 5'-D(*GP*CP*CP*TP*GP*TP*TP*AP*GP*CP*G)-3', 45-(3-AMINOPROPYL)-5,11,22,28,34-PENTAMETHYL-3,9,15,20,26,32,38,43-OCTAOXO-2,5,8,14,19,22,25,28,31,34,37,42,45,48-TETRADECAAZA-11-AZONIAHEPTACYCLO[42.2.1.1~4,7~.1~10,13~.1~21,24~.1~27,30~.1~33,36~]DOPENTACONTA-1(46),4(52),6,10(51),12,21(50),23,27(49),29,33(48),35,44(47)-DODECAENE (3 entities in total)
• 機能のキーワード: dna
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 7656.42

構造登録者

Zhang, Q.,Dwyer, T.J.,Tsui, V.,Case, D.A.,Cho, J.,Dervan, P.B.,Wemmer, D.E. (登録日: 2003-06-18, 公開日: 2004-06-29, 最終更新日: 2024-05-22)

主引用文献

Zhang, Q.,Dwyer, T.J.,Tsui, V.,Case, D.A.,Cho, J.,Dervan, P.B.,Wemmer, D.E.
NMR Structure of a Cyclic Polyamide-DNA Complex.
J.Am.Chem.Soc., 126:7958-7966, 2004

PubMed Abstract: The solution structure of a cyclic polyamide ligand complexed to a DNA oligomer, derived from NMR restrained molecular mechanics, is presented. The polyamide, cyclo-gamma-ImPyPy-gamma-PyPyPy-, binds to target DNA with a nanomolar dissociation constant as characterized by quantitative footprinting previously reported. 2D (1)H NMR data were used to generate distance restraints defining the structure of this cyclic polyamide with the DNA duplex d(5'-GCCTGTTAGCG-3'):d(5'-CGCTAACAGGC-3'). Data interpretation used complete relaxation matrix analysis of the NOESY cross-peak intensities with the program MARDIGRAS. The NMR-based distance restraints (276 total) were applied in restrained molecular dynamics calculations using a solvent model, yielding structures with an rmsd for the ligand and binding site of approximately 1 A. The resulting structures indicate some distortion of the DNA in the binding site. The constraints from cyclization lead to altered stacking of the rings in the halves of the cyclic ligand relative to unlinked complexes. Despite this, the interactions with DNA are very similar to what has been found in unlinked complexes. Measurements of ligand amide and DNA imino proton exchange rates indicate very slow dissociation of the ligand and show that the DNA can undergo opening fluctuations while the ligand is bound although the presence of the ligand decreases their frequency relative to the free DNA.

PubMed: 15212545
DOI: 10.1021/ja0373622

実験手法

SOLUTION NMR