2JPZ

Human telomere DNA quadruplex structure in K+ solution hybrid-2 form

2JPZ の概要

• エントリーDOI: 10.2210/pdb2jpz/pdb
• 関連するPDBエントリー: 2HY9 2KKA
• 分子名称: DNA (26-MER) (1 entity in total)
• 機能のキーワード: dna, quadruplex, human telomeric sequence
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 8200.27

構造登録者

Dai, J.,Carver, M.,Punchihewa, C.,Jones, R.,Yang, D. (登録日: 2007-05-25, 公開日: 2007-12-04, 最終更新日: 2024-05-01)

主引用文献

Dai, J.,Carver, M.,Punchihewa, C.,Jones, R.A.,Yang, D.
Structure of the Hybrid-2 type intramolecular human telomeric G-quadruplex in K+ solution: insights into structure polymorphism of the human telomeric sequence
Nucleic Acids Res., 35:4927-4940, 2007

PubMed Abstract: Formation of the G-quadruplex in the human telomeric sequence can inhibit the activity of telomerase, thus the intramolecular telomeric G-quadruplexes have been considered as an attractive anticancer target. Information of intramolecular telomeric G-quadruplex structures formed under physiological conditions is important for structure-based drug design. Here, we report the first structure of the major intramolecular G-quadruplex formed in a native, non-modified human telomeric sequence in K(+) solution. This is a hybrid-type mixed parallel/antiparallel-G-stranded G-quadruplex, one end of which is covered by a novel T:A:T triple capping structure. This structure (Hybrid-2) and the previously reported Hybrid-1 structure differ in their loop arrangements, strand orientations and capping structures. The distinct capping structures appear to be crucial for the favored formation of the specific hybrid-type intramolecular telomeric G-quadruplexes, and may provide specific binding sites for drug targeting. Our study also shows that while the hybrid-type G-quadruplexes appear to be the major conformations in K(+) solution, human telomeric sequences are always in equilibrium between Hybrid-1 and Hybrid-2 structures, which is largely determined by the 3'-flanking sequence. Furthermore, both hybrid-type G-quadruplexes suggest a straightforward means for multimer formation with effective packing in the human telomeric sequence and provide important implications for drug targeting of G-quadruplexes in human telomeres.

PubMed: 17626043
DOI: 10.1093/nar/gkm522

実験手法

SOLUTION NMR