HELIX GEOMETRY, HYDRATION, AND G.A MISMATCH IN A B-DNA DECAMER

HELIX GEOMETRY, HYDRATION, AND G.A MISMATCH IN A B-DNA DECAMER
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DOI:
10.1126/science.3310237
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发表时间:
1987-10-23
期刊:
影响因子:
56.9
通讯作者:
DICKERSON, RE
DICKERSON, RE
中科院分区:
综合性期刊1区
文献类型:
--
作者:
PRIVE, GG;HEINEMANN, U;DICKERSON, RE

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DNA双螺旋并不是一个规则的、毫无特征的分子。不同的碱基序列具有其自身的特殊特征,以它们影响凹槽宽度、螺旋扭曲、弯曲和机械刚度或抗弯曲性的方式。这些特殊的特征可能有助于其他分子,如阻遏物,优先阅读和识别一个碱基序列。单晶X射线结构分析开始向我们展示B-DNA家族中可能存在的各种结构。DNA十聚体C-C-A-A-G-A-T-T-G-G似乎是混合序列B-DNA的更好模型,而不是更早的C-G-C-G-A-A-T-T-C-G-C-G,后者更类似于poly(dA)··poly(dT)的区域。在十聚体中心的G.cntdot.A错配碱基对关于它们从碱基到糖的键处于反-反构象,与该序列和其他序列上的核磁共振证据一致,并且与C-G-C-G-A-A-T-T-A-G-C-G中的G.cntdot.A对报道的反-syn几何结构相反。前面在窄槽十二聚体中看到的有序水合脊,在宽槽十聚体中也有对应的水合脊,即排列在小沟壁的两串水分子,从嘌呤N3或嘧啶O2桥接到下面的糖O 4“。在G-C-G-C-G-C的硫代磷酸酯类似物中存在相同的水合链。不像脊柱,这是打破了入侵的氨基在鸟嘌呤,这些水字符串被发现在一般的,混合序列的DNA,因为它们可以通过畅通无阻的任何一侧的鸟嘌呤N2胺。脊柱和弦被认为是小沟水合作用一般模式的两个极端,这可能是使B-DNA在高水合作用下成为首选形式的主导因素。
The DNA double helix is not a regular, featureless barberpole molecule. Different base sequences have their own special signature, in the way that they influence groove width, helical twist, bending, and mechanical rigidity or resistance to bending. These special features probably help other molecules such as repressors to read and recognize one base sequence in preference to another. Single crystal x-ray structure analysis is beginning to show us the various structures possible in the B-DNA family. The DNA decamer C-C-A-A-G-A-T-T-G-G appears to be a better model for mixed-sequence B-DNA than was the earlier C-G-C-G-A-A-T-T-C-G-C-G, which is more akin to regions of poly(dA).cntdot.poly(dT). The G.cntdot.A mismatch base pairs at the center of the decamer are in the anti-anti conformation about their bonds from base to sugar, in agreement with nuclear magnetic resonance evidence on this and other sequences, and in contrast to the anti-syn geometry reported for G.cntdot.A pairs in C-G-C-G-A-A-T-T-A-G-C-G. The ordered spine of hydration seen earlier in the narrow-grooved dodecamer has its counterpart, in this wide-grooved decamer, in two strings of water molecules lining the walls of the minor groove, bridging from purine N3 or pyrimidine O2, to the following sugar O4''. The same strings of hydration are present in the phosphorothioate analog of G-C-G-C-G-C. Unlike the spine, which is broken up by the intrusion of amine groups at guanines, these water strings are found in general, mixed-sequence DNA because they can pass by unimpeded to either side of a guanine N2 amine. The spine and strings are perceived as two extremes of a general pattern of hydration of the minor groove, which probably is the dominant factor in making B-DNA the preferred form at high hydration.