4G0F

Crystal structure of the complex of a human telomeric repeat G-quadruplex and N-methyl mesoporphyrin IX (P6)

4G0F の概要

• エントリーDOI: 10.2210/pdb4g0f/pdb
• 関連するPDBエントリー: 4FXM
• 分子名称: DNA (5'-D(*AP*GP*GP*GP*TP*TP*AP*GP*GP*GP*TP*TP*AP*GP*GP*GP*TP*TP*AP*GP*GP*G)-3'), POTASSIUM ION, N-METHYLMESOPORPHYRIN, ... (4 entities in total)
• 機能のキーワード: quadruplex, n-methyl mesoporphyrin ix, dna
• 由来する生物種: Homo sapiens
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 7681.51

構造登録者

Nicoludis, J.M.,Miller, S.T.,Jeffrey, P.,Lawton, T.J.,Rosenzweig, A.C.,Yatsunyk, L.A. (登録日: 2012-07-09, 公開日: 2012-12-26, 最終更新日: 2024-02-28)

主引用文献

Nicoludis, J.M.,Miller, S.T.,Jeffrey, P.D.,Barrett, S.P.,Rablen, P.R.,Lawton, T.J.,Yatsunyk, L.A.
Optimized End-Stacking Provides Specificity of N-Methyl Mesoporphyrin IX for Human Telomeric G-Quadruplex DNA.
J.Am.Chem.Soc., 134:20446-20456, 2012

PubMed Abstract: N-methyl mesoporphyrin IX (NMM) is exceptionally selective for G-quadruplexes (GQ) relative to duplex DNA and, as such, has found a wide range of applications in biology and chemistry. In addition, NMM is selective for parallel versus antiparallel GQ folds, as was recently demonstrated in our laboratory. Here, we present the X-ray crystal structure of a complex between NMM and human telomeric DNA dAGGG(TTAGGG)(3), Tel22, determined in two space groups, P2(1)2(1)2 and P6, at 1.65 and 2.15 Å resolution, respectively. The former is the highest resolution structure of the human telomeric GQ DNA reported to date. The biological unit contains a Tel22 dimer of 5'-5' stacked parallel-stranded quadruplexes capped on both ends with NMM, supporting the spectroscopically determined 1:1 stoichiometry. NMM is capable of adjusting its macrocycle geometry to closely match that of the terminal G-tetrad required for efficient π-π stacking. The out-of-plane N-methyl group of NMM fits perfectly into the center of the parallel GQ core where it aligns with potassium ions. In contrast, the interaction of the N-methyl group with duplex DNA or antiparallel GQ would lead to steric clashes that prevent NMM from binding to these structures, thus explaining its unique selectivity. On the basis of the biochemical data, binding of NMM to Tel22 does not rely on relatively nonspecific electrostatic interactions, which characterize most canonical GQ ligands, but rather it is hydrophobic in nature. The structural features observed in the NMM-Tel22 complex described here will serve as guidelines for developing new quadruplex ligands that have excellent affinity and precisely defined selectivity.

PubMed: 23181361
DOI: 10.1021/ja3088746

実験手法

X-RAY DIFFRACTION (2.15 Å)