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|標題:||CoII(Chromomycin)₂ Complex Induces a Conformational Change of CCG Repeats from i-Motif to Base-Extruded DNA Duplex||作者:||Chen, Yu-Wen
Waring, Michael J
|關鍵字:||CCG repeats;DNA deformation;X-ray crystallography;chromomycin A3;i-motif;neurological disease;nucleotide flip-out;trinucleotide repeat DNA;Chromomycin A3;Cobalt;Coordination Complexes;Crystallography, X-Ray;DNA;Drug Discovery;Models, Molecular;Nucleic Acid Conformation;Trinucleotide Repeats||Project:||International journal of molecular sciences, Volume 19, Issue 9||摘要:||
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.
|Appears in Collections:||基因體暨生物資訊學研究所|
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