• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Journal of Molecular Biology >Comparative structural analysis by [H-1,P-31]-NMR and restrained molecular dynamics of two DNA hairpins from a strong DNA topoisomerase II cleavage site
【24h】

Comparative structural analysis by [H-1,P-31]-NMR and restrained molecular dynamics of two DNA hairpins from a strong DNA topoisomerase II cleavage site

机译：通过[H-1，P-31] -NMR比较结构分析，并从一个强大的DNA拓扑异构酶II裂解位点抑制了两个DNA发夹的分子动力学

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

The structural analysis of two single-stranded DNAs d(AGCTTATCATCGATAAGCT) (ATC-19) and d(AGCTTATCGATGATAAGCT) (GAT-19) was performed by NMR and restrained molecular dynamics. These oligonucleotides reproduce the 15-33 segment of phage pBR322 DNA, which contains a strong cleavage site for topoisomerase II coupled to the antitumor drugs VP-16 and ellipticine. Because of their partial palindromic nature, the two oligonucleotides ATC-19 and GAT-19 may fold back into stable hairpin structures, consisting of a stem of eight base-pairs and a loop of three residues. NMR assignments and conformational parameters were determined from combined 2D NOESY, COSY and H-1-P-31 spectra. Conformations of ATC-19 and GAT-19 hairpins were calculated using the X-PLOR 3.1 program. Structures were generated through simulated annealing procedures starting from 50 structures with randomized torsion angles. A good convergence was observed for ATC-19 molecules, while no consensus was found for GAT-19. Within the GAT-19 loop, the base stacking was poor and no hydrogen bond could be detected. In contrast, ATC-19 displayed a well-defined three residue loop stabilized by both extensive base stackings and hydrogen bonding between the N3 atom of the adenine ring and the amino group of the cytosine ring. The results confirm our earlier ATC-19 structure obtained by a completely different calculation procedure (JUMNA) and the higher thermal stability of ATC-19 compared to GAT-19. Moreover, due to its mismatched basepair, the ATC-19 loop may be better described as a single residue loop rather than a three residue loop. Comparison of this loop to those containing sheared purine purine base-pairs revealed striking resemblances, particularly on the backbone angle combination. Finally, the differences observed between the ATC-19 and GAT-19 structures could help toward understanding the sequential cleavage of DNA strands by topoisomerase II. (C) 1998 Academic Press. [References: 66]
机译：通过NMR对两个单链DNA d（AGCTTATCATCGATAAGCT）（ATC-19）和d（AGCTTATCGATGATAAGCT）（GAT-19）的结构进行了分析，并限制了分子动力学。这些寡核苷酸可复制噬菌体pBR322 DNA的15-33片段，该片段含有与抗肿瘤药VP-16和玫瑰树碱偶联的拓扑异构酶II的强切割位点。由于它们的部分回文性质，两个寡核苷酸ATC-19和GAT-19可能折回到稳定的发夹结构中，该结构由八个碱基对的茎和三个残基的环组成。 NMR指配和构象参数由2D NOESY，COZY和H-1-P-31组合光谱确定。使用X-PLOR 3.1程序计算ATC-19和GAT-19发夹的构象。通过模拟退火程序从50个具有随机扭转角的结构开始生成结构。对于ATC-19分子观察到良好的收敛性，而对于GAT-19则未发现共识。在GAT-19环内，碱基堆积很差，无法检测到氢键。相反，ATC-19显示出一个定义明确的三个残基环，该环通过广泛的碱基堆积和腺嘌呤环的N3原子与胞嘧啶环的氨基之间的氢键而稳定。结果证实了我们通过完全不同的计算程序（JUMNA）获得的早期ATC-19结构以及与GAT-19相比更高的ATC-19热稳定性。此外，由于其错配的碱基对，ATC-19环可更好地描述为单残基环，而不是三残基环。将该环与含有剪切的嘌呤嘌呤碱基对的环比较，发现了惊人的相似之处，尤其是在骨架角组合上。最后，在ATC-19和GAT-19结构之间观察到的差异可能有助于理解拓扑异构酶II对DNA链的顺序切割。 （C）1998年学术出版社。 [参考：66]

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号