Unique tertiary and neighbor interactions determine conservation patterns of Cis Watson-Crick A/G base-pairs.
Unique tertiary and neighbor interactions determine conservation patterns of Cis Watson-Crick A/G base-pairs.
复制标题
独特的三级和邻近相互作用决定了 Cis Watson-Crick A/G 碱基对的保守模式。
DOI：
10.1016/s0022-2836(03)00667-3
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发表时间：
2003
影响因子：
5.6
通讯作者：
Leontis,NeoclesB
中科院分区：
文献类型：
--
作者：
Sponer,Jirí;Mokdad,Ali;Sponer,JuditE;Spacková,Nad'a;Leszczynski,Jerzy;Leontis,NeoclesB
顺式Watson-Crick(W.C.)分子相互作用和保守模式的X射线、系统发育和量子化学分析对16S rRNA、23S rRNA等分子进行了A/G碱基对分析。在这些碱基对中，A和G核苷酸与它们的W.C.边相互作用，以糖苷键为导向的顺式相互作用。碱基对被两个氢键稳定，C_1‘-C_1’距离增大，G(N_2)氨基不成对。量子化学计算表明，在没有其他相互作用的情况下，由于部分自旋锥化，未配对的氨基基本上是非平面的，而整个碱基对是内部螺旋桨扭曲的，非常灵活。顺式W.C.A/G碱基对独特的分子性质使其有别于其他碱基对。它们大多出现在典型螺旋的末端，在那里它们充当螺旋和其他基序之间的界面。顺式W.C.A/G碱基对在天然RNA结构中起着至关重要的作用，具有显著的序列保守性。保守的关键贡献是由未配对的G(N2)氨基提供的，该基团参与了晶体结构中广泛的三级和邻近接触。它们中的许多在鸟嘌呤碱基平面外定向，并利用G(N2)的部分自锥作用。没有A/G到G/A的协变，除了G(N_2)位外，它将是完全等量的。相反，由于G/U摆动碱基对在与顺式W.C.G/A碱基对相同的位置上有一个不成对的氨基，因此G/A到G/U共变的发生相当频繁。当没有第三或邻近相互作用时，顺式W.C.A/G碱基对是不保守的。要获得顺式W.C.A/G碱基对相互作用和系统发育模式的正确图像，需要在单个氢键和接触的水平上详细分析分子结构和相互作用的能量学之间的关系。
X-ray, phylogenetic and quantum chemical analysis of molecular interactions and conservation patterns of cis Watson–Crick (W.C.) A/G base-pairs in 16S rRNA, 23S rRNA and other molecules was carried out. In these base-pairs, the A and G nucleotides interact with their W.C. edges with glycosidic bonds oriented cis relative to each other. The base-pair is stabilised by two hydrogen bonds, the C1′–C1′ distance is enlarged and the G(N2) amino group is left unpaired. Quantum chemical calculations show that, in the absence of other interactions, the unpaired amino group is substantially non-planar due to its partial sp3pyramidalization, while the whole base-pair is internally propeller twisted and very flexible. The unique molecular properties of the cis W.C. A/G base-pairs make them distinct from other base-pairs. They occur mostly at the ends of canonical helices, where they serve as interfaces between the helix and other motifs. The cis W.C. A/G base-pairs play crucial roles in natural RNA structures with salient sequence conservation patterns. The key contribution to conservation is provided by the unpaired G(N2) amino group that is involved in a wide range of tertiary and neighbor contacts in the crystal structures. Many of them are oriented out of the plane of the guanine base and utilize the partial sp3pyramidalization of the G(N2). There is a lack of A/G to G/A covariation, which, except for the G(N2) position, would be entirely isosteric. On the contrary, there is a rather frequent occurrence of G/A to G/U covariation, as the G/U wobble base-pair has an unpaired amino group in the same position as the cis W.C. G/A base-pair. The cis W.C. A/G base-pairs are not conserved when there is no tertiary or neighbor interaction. Obtaining the proper picture of the interactions and phylogenetic patterns of the cis W.C. A/G base-pairs requires a detailed analysis of the relation between the molecular structures and the energetics of interactions at a level of single H-bonds and contacts.