Major and minor groove conformations of DNA trimers modified on guanine or adenine by 4-aminobiphenyl: adenine adducts favor the minor groove.
Major and minor groove conformations of DNA trimers modified on guanine or adenine by 4-aminobiphenyl: adenine adducts favor the minor groove.
复制标题
通过 4-氨基联苯：腺嘌呤加合物对鸟嘌呤或腺嘌呤进行修饰的 DNA 三聚体的大沟和小沟构象有利于小沟。
DOI：
10.1021/tx00043a016
复制
发表时间：
1995
影响因子：
4.1
通讯作者：
Broyde,S
中科院分区：
文献类型：
--
作者：
Shapiro,R;Ellis,S;Hingerty,BE;Broyde,S
本文研究了鸟嘌呤或腺嘌呤C-8位上的4-氨基联苯修饰对双链DNA三聚体构象的影响。我们使用的序列在中心碱基对上有修饰的嘌呤，在外部碱基对上有所有16个可能的相邻序列。用分子力学程序DUPLEX进行了最小势能计算，对这些加合物的构象空间进行了调查，共使用了1280个修饰的鸟嘌呤系列和修饰的腺嘌呤系列的起始结构。构象的家庭，其中绑定的4-氨基联苯位于DNA大沟，并在小沟，位于腺嘌呤和鸟嘌呤修饰。在修饰的鸟嘌呤系列中，大沟和小沟家族在能量上大致相当，并且序列背景决定了在特定情况下哪个更稳定。然而，在修饰的腺嘌呤序列中，小沟结构比所有序列的大沟结构稳定10 kcal/mol以上。因此，小沟加合物提供了腺嘌呤修饰系列中的大部分全局最小值。该结果可能与先前的诱变研究相关[Lasko et al.（1988）J.Biol.Chem.263，15429-15435]，其中最频繁出现的热点位于序列GAT中的腺嘌呤处。
We have studied the conformational effects of 4-aminobiphenyl modification at C-8 of guanine or adenine on double-stranded DNA trimers. We used sequences with the modified purineat the central base pair and all 16 possible neighboring sequences at the outer pairs. Minimized potential energy calculations were carried out using the molecular mechanics program DUPLEX to survey the conformation space of these adducts, using a total of 1280 starting structures both in the modified guanine series and inthe modified adenineseries. Conformer families in which the bound 4-aminobiphenyl was located in the DNA major groove, and in the minor groove, were located for both adenine and guanine modification. In the modified guanine series, the major and minor groove families were roughly comparable in energy, and the sequence context determined which was more stable in a particular case. In the modified adenine series, however, the minor groove structure was more than 10 kcal/mol more stable than the major groove structurefor all sequences. As a result, minor groove adducts provided most of the global minima in the adenine-modified series. This result may be relevant to a previous mutagenesis study [Lasko et al.(1988) J. Biol. Chem. 263, 15429-15435] in which the hot spot of most frequent occurrence was located at an adenine, in the sequence GAT.