Bhaumik Sukesh R, Chary Kandala V R
Department of Chemical Science, Tata Institute of Fundamental Research, Homi Bhabha Road, Colaba, Mumbai-400005, India.
J Biomol Struct Dyn. 2002 Oct;20(2):199-206. doi: 10.1080/07391102.2002.10506835.
Despite major advances in characterizing purine(R)-purine(R), purine(R)-pyrimidine(Y) and pyrimidine(Y)-pyrimidine(Y) mismatches in DNA, there have not been any structural studies on a synthetic DNA duplex containing several different mispairs. Here, using NMR restrained molecular mechanics and dynamics simulations we have structurally characterized a 12 nucleotide long antiparallel DNA duplex with three different mispairs, namely A+-C, G-T and T-C. Our results show that the overall conformation of the antiparallel DNA duplex is B-DNA-like with slight structural distortions at or near the mispairs' sites. All these mispairs are properly stacked with their flanking base pairs. Each mispair is stabilized by two hydrogen bonds and the decreasing order of the hydrogen-bonding interactions is G-T>T-C>A+-C. G-T mispair has smaller configurational space while the structure is slightly bent at A+-C mispair's site. Overall, this study is the first ever structural characterization of a DNA duplex with three different mismatched base pairs and throws light upon the local conformations of the three mispairs present in the DNA duplex.
尽管在表征DNA中的嘌呤（R）-嘌呤（R）、嘌呤（R）-嘧啶（Y）和嘧啶（Y）-嘧啶（Y）错配方面取得了重大进展，但尚未对包含几种不同错配的合成DNA双链体进行任何结构研究。在这里，我们使用核磁共振约束分子力学和动力学模拟，对一个含有三个不同错配（即A+-C、G-T和T-C）的12个核苷酸长的反平行DNA双链体进行了结构表征。我们的结果表明，反平行DNA双链体的整体构象类似B-DNA，在错配位点或其附近有轻微的结构扭曲。所有这些错配都与其侧翼碱基对正确堆积。每个错配由两个氢键稳定，氢键相互作用的递减顺序为G-T>T-C>A+-C。G-T错配具有较小的构象空间，而在A+-C错配位点结构略有弯曲。总体而言，这项研究首次对具有三个不同错配碱基对的DNA双链体进行了结构表征，并揭示了DNA双链体中存在的三个错配的局部构象。
