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


ABSTRACT: 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)?. Biophysical experiments reveal that CCG trinucleotide repeats provide favorable binding sites for CoII(Chro)?. 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.

SUBMITTER: Chen YW 

PROVIDER: S-EPMC6164834 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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

Chen Yu-Wen YW   Satange Roshan R   Wu Pei-Ching PC   Jhan Cyong-Ru CR   Chang Chung-Ke CK   Chung Kuang-Ren KR   Waring Michael J MJ   Lin Sheng-Wei SW   Hsieh Li-Ching LC   Hou Ming-Hon MH  

International journal of molecular sciences 20180917 9


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 (Co<sup>II</sup>)-mediated dimer of chromomycin A3, Co<sup>II</sup>(Chro)₂. Biophysical experiments reveal that CCG trinucleotide repeats provide favorable binding sites for Co<sup>II</sup>(Chro)₂. In addition,  ...[more]

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