Entropy-driven conformational transition of flexible Z-DNA to a novel non-B helix by double-methylated guanosine

被引:0
作者
Oh, Kwang-Im [1 ,2 ]
Jin, Ho-Seong [1 ,2 ]
Balasubramaniyam, Thananjeyan [1 ,2 ]
Shin, Ji-Yeon [3 ,4 ]
Choi, Seo-Ree [1 ,2 ]
Seo, Young Jun [5 ]
Kim, Byeong-Seon [2 ,6 ]
Seo, Yeo-Jin [1 ,2 ]
Kwon, Seung-Ryong [1 ,2 ]
Kim, Nak-Kyoon
Lee, Joon-Hwa [1 ,2 ]
机构
[1] Gyeongsang Natl Univ, Dept Chem, Jinju 52828, Gyeongnam, South Korea
[2] Gyeongsang Natl Univ, RINS, Jinju 52828, Gyeongnam, South Korea
[3] Korea Univ, Dept Life Sci, Seoul 02841, South Korea
[4] Korea Inst Sci & Technol, Adv Anal Data Ctr, Seoul 02792, South Korea
[5] Jeonbuk Natl Univ, Dept Chem, Jeonbuk 54596, South Korea
[6] Gyeongsang Natl Univ, Dept Chem Educ, Jinju 52828, Gyeongnam, South Korea
基金
新加坡国家研究基金会;
关键词
Base modified DNA; Helical parameter; Z; -DNA; DNA dynamics; NMR; MOLECULAR-STRUCTURE; CRYSTAL-STRUCTURE; XPLOR-NIH; BINDING; OLIGONUCLEOTIDES; RESOLUTION; KINETICS; SPECTRA; PROTEIN; PROBE;
D O I
10.1016/j.molliq.2023.122071
中图分类号
O64 [物理化学(理论化学)、化学物理学];
学科分类号
070304 ; 081704 ;
摘要
Developing chemical modifications of DNA to find drug targets is challenging. Here, we incorporated doublemethylated guanosine into a DNA duplex and determined its solution structure using NMR and restrained molecular dynamics. The double-methylation of guanosine promotes aberrantly distorted Z-DNA with a widened groove space. This flexible Z-DNA exhibited slow conformational exchange (second time-scale) with a novel helical structure (denoted as tBZ-form). We find three characteristics of the Z-to-tBZ transition: 1) syn-to-syn glycosidic conformation (Z-to-non-B); 2) loss of left-handedness (that is, Z-to-non-Z); 3) entropic gain of the Z-totBZ transition. We anticipate that this flexible Z-DNA can be considered a novel target for drug discovery and that the Z-to-tBZ transition will provide new insights into structural diversity.
引用
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页数:9
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