Adrian Michael, Winnerdy Fernaldo Richtia, Heddi Brahim, Phan Anh Tuân
Division of Physics and Applied Physics, School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore, Singapore.
Division of Physics and Applied Physics, School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore, Singapore.
Biophys J. 2017 Aug 22;113(4):775-784. doi: 10.1016/j.bpj.2017.05.053.
Nucleic acids are dynamic molecules whose functions may depend on their conformational fluctuations and local motions. In particular, amino groups are dynamic components of nucleic acids that participate in the formation of various secondary structures such as G-quadruplexes. Here, we present a cost-efficient NMR method to quantify the rotational dynamics of guanine amino groups in G-quadruplex nucleic acids. An isolated spectrum of amino protons from a specific tetrad-bound guanine can be extracted from the nuclear Overhauser effect spectroscopy spectrum based on the close proximity between the intra-residue imino and amino protons. We apply the method in different structural contexts of G-quadruplexes and their complexes. Our results highlight the role of stacking and hydrogen-bond interactions in restraining amino-group rotation. The measurement of the rotation rate of individual amino groups could give insight into the dynamic processes occurring at specific locations within G-quadruplex nucleic acids, providing valuable probes for local structure, dynamics, and ligand binding.
核酸是动态分子，其功能可能取决于其构象波动和局部运动。特别是，氨基是核酸的动态组成部分，参与各种二级结构（如G-四链体）的形成。在这里，我们提出了一种经济高效的核磁共振方法来量化G-四链体核酸中鸟嘌呤氨基的旋转动力学。基于残基内亚氨基和氨基质子之间的紧密接近，可以从核Overhauser效应光谱中提取特定四联体结合鸟嘌呤的氨基质子的孤立光谱。我们将该方法应用于G-四链体及其复合物的不同结构背景中。我们的结果突出了堆积和氢键相互作用在限制氨基旋转中的作用。单个氨基旋转速率的测量可以深入了解G-四链体核酸内特定位置发生的动态过程，为局部结构、动力学和配体结合提供有价值的探针。
