3QSF

The first crystal structure of a human telomeric G-quadruplex DNA bound to a metal-containing ligand (a nickel complex)

3QSF の概要

• エントリーDOI: 10.2210/pdb3qsf/pdb
• 関連するPDBエントリー: 1K8P 1KF1 2HRI 3CCO 3CDM 3CE5 3QSC
• 分子名称: 5'-D(*AP*GP*GP*GP*TP*TP*AP*GP*GP*GP*TP*T)-3', POTASSIUM ION, [2,2'-{(4,5-difluorobenzene-1,2-diyl)bis[(nitrilo-kappaN)methylylidene]}bis{5-[2-(piperidin-1-yl)ethoxy]phenolato-kappa O}(2-)]nickel (II), ... (4 entities in total)
• 機能のキーワード: parallel, telomere, nickel, drug, dna, metal complex
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 4554.14

構造登録者

Campbell, N.H.,Abd Karim, N.H.,Parkinson, G.N.,Vilar, R.,Neidle, S. (登録日: 2011-02-21, 公開日: 2011-12-07, 最終更新日: 2023-09-13)

主引用文献

Campbell, N.H.,Karim, N.H.,Parkinson, G.N.,Gunaratnam, M.,Petrucci, V.,Todd, A.K.,Vilar, R.,Neidle, S.
Molecular basis of structure-activity relationships between salphen metal complexes and human telomeric DNA quadruplexes.
J.Med.Chem., 55:209-222, 2012

PubMed Abstract: The first X-ray crystal structures of nickel(II) and copper(II) salphen metal complexes bound to a quadruplex DNA are presented. Two structures have been determined and show that these salphen-metal complexes bind to human telomeric quadruplexes by end-stacking, with the metal in each case almost in line with the potassium ion channel. Quadruplex and duplex DNA binding is presented for these two and other related salphen complexes, all with side-chains terminating in pyrrolidino end-groups and differing patterns of substitution on the salphen core. The crystal structures are able to provide rationalizations for the structure-activity data, and in particular for the superior quadruplex-binding of the nickel complexes compared to that of the copper-containing ones. The complexes show significant antiproliferative activity for the compounds in a panel of cancer cell lines. They also show telomerase inhibitory activity in the telomerase TRAP-LIG assay.

PubMed: 22112241
DOI: 10.1021/jm201140v

実験手法

X-RAY DIFFRACTION (2.4 Å)