Sequence-Selective Minor Groove Recognition of a DNA Duplex Containing Synthetic Genetic Components.
Sequence-Selective Minor Groove Recognition of a DNA Duplex Containing Synthetic Genetic Components.
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DOI：
10.1021/jacs.8b12444
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发表时间：
2019-05
影响因子：
15
通讯作者：
G. Padroni;Jamie M. Withers;A. Taladriz-Sender;L. Reichenbach;J. Parkinson;G. Burley
中科院分区：
文献类型：
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作者：
G. Padroni;Jamie M. Withers;A. Taladriz-Sender;L. Reichenbach;J. Parkinson;G. Burley
小沟识别的DNA双链体含有合成的遗传信息的发夹吡咯咪唑聚酰胺的结构基础进行了说明。当咪唑单元与P核苷酸对齐时，发夹聚酰胺诱导含有非天然P·Z碱基对的DNA双链体的更高的熔融稳定性。核磁共振结构研究表明，相对于完全由沃森-克里克碱基对组成的DNA双链体，两个独立的P·Z对的掺入使该合成遗传信息位点的小沟扩大，而大沟略微变窄。吡咯-咪唑聚酰胺与含P·Z的DNA双链体结合形成稳定的复合物，有效地模拟了G·C对。通过聚酰胺识别P·Z对的小沟的结构标志是降低由聚酰胺与DNA双链体结合诱导的变构畸变水平。了解影响含有合成遗传组分的DNA的小沟识别的分子决定簇为进一步开发用于合成生物学应用的非天然碱基对提供了基础。
The structural basis of minor groove recognition of a DNA duplex containing synthetic genetic information by hairpin pyrrole-imidazole polyamides is described. Hairpin polyamides induce a higher melting stabilization of a DNA duplex containing the unnatural P·Z base-pair when an imidazole unit is aligned with a P nucleotide. An NMR structural study showed that the incorporation of two isolated P·Z pairs enlarges the minor groove and slightly narrows the major groove at the site of this synthetic genetic information, relative to a DNA duplex consisting entirely of Watson-Crick base-pairs. Pyrrole-imidazole polyamides bind to a P·Z-containing DNA duplex to form a stable complex, effectively mimicking a G·C pair. A structural hallmark of minor groove recognition of a P·Z pair by a polyamide is the reduced level of allosteric distortion induced by binding of a polyamide to a DNA duplex. Understanding the molecular determinants that influence minor groove recognition of DNA containing synthetic genetic components provides the basis to further develop unnatural base-pairs for synthetic biology applications.