Co(II)(Chromomycin)₂ Complex Induces a Conformational Change of CCG Repeats from i-Motif to Base-Extruded DNA Duplex.

Co(II)(Chromomycin)₂ Complex Induces a Conformational Change of CCG Repeats from i-Motif to Base-Extruded DNA Duplex.
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DOI:
10.3390/ijms19092796
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发表时间:
2018-09-17
影响因子:
5.6
通讯作者:
Hou MH
Hou MH
中科院分区:
生物学2区
文献类型:
--
作者:
Chen YW;Satange R;Wu PC;Jhan CR;Chang CK;Chung KR;Waring MJ;Lin SW;Hsieh LC;Hou MH

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我们已经报道了在没有配体的情况下,含有CCG重复的DNA序列形成稳定的I基序四链结构的倾向。在这里,我们证明了当I-基序DNA序列与(CoII)介导的色霉素A3的二聚体CoII(Chro)2结合时,I-基序DNA序列可以转变为具有GGCC四核苷酸链的碱基挤出双链结构。生物物理实验表明,CCG三核苷酸重复序列为CoII(Chro)2提供了有利的结合部位。此外,水的水合作用和二价金属离子(CoII)的相互作用在CCG三核苷酸重复序列(TNRs)的稳定中也起着至关重要的作用。我们的数据为设计治疗由重复扩张引起的神经系统疾病的新的治疗策略提供了有用的结构信息。
We have reported the propensity of a DNA sequence containing CCG repeats to form a stable i-motif tetraplex structure in the absence of ligands. Here we show that an i-motif DNA sequence may transition to a base-extruded duplex structure with a GGCC tetranucleotide tract when bound to the (CoII)-mediated dimer of chromomycin A3, CoII(Chro)2. Biophysical experiments reveal that CCG trinucleotide repeats provide favorable binding sites for CoII(Chro)2. In addition, water hydration and divalent metal ion (CoII) interactions also play a crucial role in the stabilization of CCG trinucleotide repeats (TNRs). Our data furnish useful structural information for the design of novel therapeutic strategies to treat neurological diseases caused by repeat expansions.
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发表时间: 1991-12-20
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