• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Journal of Biomolecular Structure and Dynamics >Insights into protein - DNA interactions, stability and allosteric communications: a computational study of mutSalpha-DNA recognition complexes.
【24h】

Insights into protein - DNA interactions, stability and allosteric communications: a computational study of mutSalpha-DNA recognition complexes.

机译：深入了解蛋白质-DNA相互作用，稳定性和变构通讯：mutSalpha-DNA识别复合物的计算研究。

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

DNA mismatch repair proteins (MMR) maintain genetic stability by recognizing and repairing mismatched bases and insertion/deletion loops mistakenly incorporated during DNA replication, and initiate cellular response to certain types of DNA damage. Loss of MMR in mammalian cells has been linked to resistance to certain DNA damaging chemotherapeutic agents, as well as to increase risk of cancer. Mismatch repair pathway is considered to involve the concerted action of at least 20 proteins. The most abundant MMR mismatch-binding factor in eukaryotes, MutSalpha, recognizes and initiates the repair of base-base mismatches and small insertion/deletion. We performed molecular dynamics simulations on mismatched and damaged MutSalpha-DNA complexes. A comprehensive DNA binding site analysis of relevant conformations shows that MutSalpha proteins recognize the mismatched and platinum cross-linked DNA substrates in significantly different modes. Distinctive conformational changes associated with MutSalpha binding to mismatched and damaged DNA have been identified and they provide insight into the involvement of MMR proteins in DNA-repair and DNA-damage pathways. Stability and allosteric interactions at the heterodimer interface associated with the mismatch and damage recognition step allow for prediction of key residues in MMR cancer-causing mutations. A rigorous hydrogen bonding analysis for ADP molecules at the ATPase binding sites is also presented. Due to extended number of known MMR cancer causing mutations among the residues proved to make specific contacts with ADP molecules, recommendations for further studies on similar mutagenic effects were made.
机译：DNA错配修复蛋白（MMR）通过识别和修复错配的碱基以及在DNA复制过程中错误掺入的插入/缺失环来维持遗传稳定性，并启动对某些类型DNA损伤的细胞反应。哺乳动物细胞中MMR的丧失与对某些破坏DNA的化学治疗剂的抗性有关，并增加了患癌症的风险。错配修复途径被认为涉及至少20种蛋白质的协同作用。真核生物中最丰富的MMR错配结合因子MutSalpha识别并启动碱基错配和小插入/缺失的修复。我们对错配和损坏的MutSalpha-DNA复合物进行了分子动力学模拟。对相关构象进行的全面DNA结合位点分析表明，MutSalpha蛋白以明显不同的方式识别错配和铂交联的DNA底物。已发现与MutSalpha与错配和受损DNA结合相关的独特构象变化，它们为MMR蛋白在DNA修复和DNA损伤途径中的参与提供了见识。与错配和损伤识别步骤相关的异二聚体界面处的稳定性和变构相互作用可以预测MMR致癌突变中的关键残基。还介绍了对ADP分子在ATPase结合位点的严格氢键分析。由于大量已知的MMR癌症导致残基之间的突变被证明与ADP分子发生特异性接触，因此建议对类似诱变作用进行进一步研究。

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