The 1.19 Å X-ray structure of 2′-O-Me(CGCGCG)2 duplex shows dehydrated RNA with 2-methyl-2,4-pentanediol in the minor groove
The 1.19 Å X-ray structure of 2′-O-Me(CGCGCG)2 duplex shows dehydrated RNA with 2-methyl-2,4-pentanediol in the minor groove
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DOI：
10.1093/nar/29.20.4144
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发表时间：
2001-10-15
影响因子：
14.9
通讯作者：
Adamiak, RW
中科院分区：
文献类型：
--
作者：
Adamiak, DA;Rypniewski, WR;Adamiak, RW
2'-O-Me(CGCGCG)(2) 的晶体和分子结构已在 100 K、1.19 埃分辨率下使用同步加速器辐射测定。空间群 P3(2)12 中的结构是半圈右旋螺旋，包含两个结合在小沟中的 2-甲基-2,4-戊二醇 (MPD) 分子。结构偏离A型RNA。双链体过度缠绕，平均每圈 9.7 bp，其特征是具有 C3'-内糖褶皱、非常低的碱基对上升以及高螺旋扭曲和倾斜角。该结构包含 65 个有序水分子。由于疏水性 2'-O-甲基的存在，在小沟中仅观察到单排水分子。该结构中有多达五个镁离子。其中两个位于主沟中，通过其水合球与鸟苷残基的 O-6 和 N-7 以及胞苷残基的 N-4 相互作用。这项工作提供了核酸与 MPD 分子相互作用的第一个例子，MPD 被用作沉淀剂、冷冻溶剂和分辨率增强剂。两个 MPD 分子侵入小沟中的水合网络，各自在其仲羟基和鸟苷残基的外氨基官能团之间形成氢键。 P3212 和 P6(1)22 晶体中 2'-O-Me(CGCGCG)(2) 结构的比较描绘了小沟内水网络对 MPD 脱水的稳定性，并且对于评估控制小分子与 RNA 结合的因素很有意义。 MPD 侵入 2'-O-Me(CGCGCG)2 小沟，讨论了 RNA 脱水（Z-RNA 形成的先决条件）。
The crystal and molecular structure of 2'-O-Me(CGCGCG)(2) has been determined at 1.19 Angstrom resolution, at 100 K, using synchrotron radiation. The structure in space group P3(2)12 is a half-turn right-handed helix that includes two 2-methyl-2,4-pentanediol (MPD) molecules bound in the minor groove. The structure deviates from A-form RNA. The duplex is overwound with an average value of 9.7 bp per turn, characterised as having a C3'-endo sugar pucker, very low base pair rise and high helical twist and inclination angles. The structure includes 65 ordered water molecules. Only a single row of water molecules is observed in the minor groove due to the presence of hydrophobic 2'-O-methyl groups. As many as five magnesium ions are located in the structure. Two are in the major groove and interact with O-6 and N-7 of guanosine and N-4 of cytidine residues through their hydration spheres. This work provides the first example of molecular interactions of nucleic acids with MPD, which was used as a precipitant, cryosolvent and resolution enhancing agent. The two MPD molecules intrude into the hydration network in the minor groove, each forming hydrogen bonds between their secondary hydroxyl group and exo-amino functions of guanosine residues. Comparison of the 2'-O-Me(CGCGCG)(2) structure in the P3212 and P6(1)22 crystals delineates stability of the Water network within the minor groove to dehydration by MPD and is of interest for evaluating factors governing small molecule binding to RNA. Intrusion of MPD into the minor groove of 2'-O-Me(CGCGCG)2 is discussed with respect to RNA dehydration, a prerequisite of Z-RNA formation.