Structure of the intramolecular human telomeric G-quadruplex in potassium solution: a novel adenine triple formation.

Structure of the intramolecular human telomeric G-quadruplex in potassium solution: a novel adenine triple formation.
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DOI:
10.1093/nar/gkm009
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发表时间:
2007
影响因子:
14.9
通讯作者:
Yang D
Yang D
中科院分区:
生物学2区
文献类型:
--
作者:
Dai J;Punchihewa C;Ambrus A;Chen D;Jones RA;Yang D

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我们报告的核磁共振溶液结构的分子内G-四链体形成的端粒DNA在K+。端粒G-四链体由三个G-四链体组成,它们通过混合的平行-反平行G-链连接,底部的两个G-四链体具有相同的G-排列(反:反:顺:反),顶部的G-四链体具有相反的G-排列(顺:顺:反:顺)。三个TTA环段采用不同的构象,第一个TTA假定双链反转环构象,第二个和第三个TTA假定侧环构象。NMR结构非常明确,包括三个TTA环和5′和3′端的两个侧翼序列。我们的研究表明,这三个环区域与核心G-四联体以一种特定的方式相互作用,这种方式定义并稳定了K+中独特的人类端粒G-四联体结构。值得注意的是,一个新的腺嘌呤三重平台形成与三个天然存在的腺嘌呤残基,A21,A3和A9,加盖的杂交型端粒G-四链体的顶部四联体。这种腺嘌呤三联体可能在K+中形成稳定的人类端粒G-四链体结构中发挥重要作用。在K+中形成的独特的人类端粒G-四链体结构表明它可以特异性地用于抗癌药物设计。
We report the NMR solution structure of the intramolecular G-quadruplex formed in human telomeric DNA in K+. The hybrid-type telomeric G-quadruplex consists of three G-tetrads linked with mixed parallel–antiparallel G-strands, with the bottom two G-tetrads having the same G-arrangement (anti:anti:syn:anti) and the top G-tetrad having the reversed G-arrangement (syn:syn:anti:syn). The three TTA loop segments adopt different conformations, with the first TTA assuming a double-chain-reversal loop conformation, and the second and third TTA assuming lateral loop conformations. The NMR structure is very well defined, including the three TTA loops and the two flanking sequences at 5′- and 3′-ends. Our study indicates that the three loop regions interact with the core G-tetrads in a specific way that defines and stabilizes the unique human telomeric G-quadruplex structure in K+. Significantly, a novel adenine triple platform is formed with three naturally occurring adenine residues, A21, A3 and A9, capping the top tetrad of the hybrid-type telomeric G-quadruplex. This adenine triple is likely to play an important role in the formation of a stable human telomeric G-quadruplex structure in K+. The unique human telomeric G-quadruplex structure formed in K+ suggests that it can be specifically targeted for anticancer drug design.
DOI: 10.1074/jbc.m404053200
发表时间: 2004-10-29
影响因子: 4.8
作者:
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发表时间: 2004-01-01
影响因子: 14.9
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DOI: 10.1093/nar/gkl348
发表时间: 2006
影响因子: 14.9
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