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首页> 外文期刊>Journal of Molecular Biology >Structure of a beta-alanine-linked polyamide bound to a full helical turn of purine tract DNA in the 1:1 motif.
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Structure of a beta-alanine-linked polyamide bound to a full helical turn of purine tract DNA in the 1:1 motif.

机译：β-丙氨酸连接的聚酰胺的结构，以1：1的基序与嘌呤束DNA的完整螺旋形结合。

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摘要

Polyamides composed of N-methylpyrrole (Py), N-methylimidazole (Im) and N-methylhydroxypyrrole (Hp) amino acids linked by beta-alanine (beta) bind the minor groove of DNA in 1:1 and 2:1 ligand to DNA stoichiometries. Although the energetics and structure of the 2:1 complex has been explored extensively, there is remarkably less understood about 1:1 recognition beyond the initial studies on netropsin and distamycin. We present here the 1:1 solution structure of ImPy-beta-Im-beta-ImPy-beta-Dp bound in a single orientation to its match site within the DNA duplex 5'-CCAAAGAGAAGCG-3'.5'-CGCTTCTCTTTGG-3' (match site in bold), as determined by 2D (1)H NMR methods. The representative ensemble of 12 conformers has no distance constraint violations greater than 0.13 A and a pairwise RMSD over the binding site of 0.80 A. Intermolecular NOEs place the polyamide deep inside the minor groove, and oriented N-C with the 3'-5' direction of the purine-rich strand. Analysis of the high-resolution structure reveals the ligand bound 1:1 completely within the minor groove for a full turn of the DNA helix. The DNA is B-form (average rise=3.3 A, twist=38 degrees ) with a narrow minor groove closing down to 3.0-4.5 A in the binding site. The ligand and DNA are aligned in register, with each polyamide NH group forming bifurcated hydrogen bonds of similar length to purine N3 and pyrimidine O2 atoms on the floor of the minor groove. Each imidazole group is hydrogen bonded via its N3 atom to its proximal guanine's exocyclic amino group. The important roles of beta-alanine and imidazole for 1:1 binding are discussed.
机译：由N-甲基吡咯（Py），N-甲基咪唑（Im）和N-甲基羟基吡咯（Hp）氨基酸与β-丙氨酸（β）连接而成的聚酰胺将DNA的1：1和2：1配体的小沟与DNA结合化学计量。尽管已经广泛研究了2：1配合物的能量学和结构，但对Netropsin和Distamycin的初步研究仍很少了解1：1识别。我们在这里介绍的ImPy-β-Im-β-ImPy-β-Dp的1：1溶液结构以单一方向与其DNA双链体5'-CCAAAGAGAAGCG-3'.5'-CGCTTCTCTTTGG-3内的匹配位点结合通过2D（1）H NMR方法确定的'（匹配位置为粗体）。 12个构象异构体的代表性集合体没有大于0.13 A的距离约束违反，并且在0.80 A的结合位点上成对存在RMSD。分子间的NOE将聚酰胺深置于小凹槽内，并以3'-5'方向定向NC富含嘌呤的链。对高分辨率结构的分析表明，DNA螺旋的完整旋转使配体完全以1：1的方式结合在小沟中。 DNA是B型（平均上升= 3.3 A，扭曲= 38度），在结合位点有一条狭窄的小沟，封闭至3.0-4.5A。配体和DNA对齐排列，每个聚酰胺NH基团在小沟的底部形成与嘌呤N3和嘧啶O2原子相似长度的分叉氢键。每个咪唑基团通过其N3原子与近端鸟嘌呤的环外氨基氢键合。讨论了β-丙氨酸和咪唑对于1：1结合的重要作用。

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