Rules governing the orientation of the 2'-hydroxyl group in RNA
Rules governing the orientation of the 2'-hydroxyl group in RNA
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DOI：
10.1006/jmbi.1997.1370
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发表时间：
1997-11-21
影响因子：
5.6
通讯作者：
Westhof, E
中科院分区：
文献类型：
--
作者：
Auffinger, P;Westhof, E
分子动力学模拟表明，在C-3 '-endo糖puckers中，只有三个方向可接近RNA分子的2'-羟基：（i）朝向相同糖的O-3 '，（ii）朝向O-4'，和（iii）朝向浅沟碱基原子。在罕见的C-2-endo糖puckers，朝向O3'原子的相同的糖的取向是强烈的青睐。令人惊讶的是，在螺旋区，经常建议的链内O-2 '-H（n）... O-4 '（n + 1）相互作用未被发现，这一观察导致了轴向C-H相互作用的检测。C-2 '-H-2'（n）基团和O-4 '（n + 1）原子之间的O相互作用有助于RNA螺旋区的稳定。随后对RNA和A-DNA螺旋的晶体结构的分析完全支持这一发现。特定的水合模式也被认为在RNA结构的稳定中起着重要作用。在RNA的浅沟中，被称为有利的RNA或蛋白质结合区域，三个明确的水合位点位于O-2'原子周围。这些水合位点被与主体交换的水分子占据，在脱水后构成RNA与核酸、蛋白质或药物之间特异性相互作用的锚点。因此，2 '-羟基不被轴向稳定化所独占的事实，连同其水样行为，促进了涉及RNA螺旋区域的复合物形成。(C)出版社：Academic Press Limited。
Molecular dynamics simulations reveal that, in C-3'-endo sugar puckers, only three orientations are accessible to the 2'-hydroxyl groups distinctive of RNA molecules: towards (i) the O-3', (ii) the O-4' of the same sugar, and (iii) the shallow groove base atoms. Ln the rarer C-2-endo sugar puckers, orientations towards the O3' atom of the same sugar are strongly favoured. Surprisingly, in helical regions, the frequently suggested intrastrand O-2'-H(n)...O-4'(n + 1) interaction is not found. This observation led to the detection of an axial C-H...O interaction between the C-2'-H-2'(n) group and the O-4'(n + 1) atom contributing to the stabilization of RNA helical regions. Subsequent analysis of crystallographic structures of both RNA and A-DNA helices fully supports this finding. Specific hydration patterns are also thought to play a significant role in the stabilization of RNA structures. In the shallow groove of RNA, known as a favourable RNA or protein-binding region, three well-defined hydration sites are located around the O-2' atom. These hydration sites, occupied by water molecules exchanging with the bulk, constitute, after dehydration, anchor points for specific interactions between RNA and nucleic acids, proteins or drugs. Therefore, the fact that the 2'-hydroxyl group is not monopolised by axial stabilization, together with its water-like behaviour, facilitates complex formation involving RNA helical regions. (C) 1997 Academic Press Limited.