• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Journal of Molecular Biology >On the Allosteric Effect of nsSNPs and the Emerging Importance of Allosteric Polymorphism
【24h】

On the Allosteric Effect of nsSNPs and the Emerging Importance of Allosteric Polymorphism

机译：关于NSSNPS的变构效应与颠振多态性的新兴重要性

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 molecular mechanisms of pathological non-synonymous single-nucleotide polymorphisms are still the object of intensive research. To this end, we explore here whether non-synonymous single-nucleotide polymorphisms can work via allosteric mechanisms. Using structure-based statistical mechanical model of allostery and analyzing energetics of the effects of mutations in a set of 27 proteins with at least 50 pathological SNPs in each molecule, we found that, indeed, some SNPs can work allosterically. We illustrate the molecular basis of disease phenotypes caused by allosteric SNPs with the case studies of human galactose 1-phosphate uridyltransferase (GALT) and glucose-6-phosphate dehydrogenase (G6PD). We also found that mutations of a number of other residues in the protein may cause modulation comparable to those observed for known pathological SNPs. In order to explain this, we propose a notion of allosteric polymorphism, which implies the presence of a number of critical positions in the protein sequence, whose mutations can allosterically disrupt the protein function and result in a disease phenotype. We conclude that the emerging importance of allosteric polymorphism calls for the development of computational framework for analyzing the allosteric effects of mutations and their role in the modulation of protein activity. (C) 2019 Elsevier Ltd. All rights reserved.
机译：病理非同义的单核苷酸多态性的分子机制仍然是深入研究的对象。为此，我们在这里探讨非同义单核苷酸多态性是否能够通过变构机制起作用。使用变构效应的基于结构的统计力学模型和一组27种蛋白与每个分子中至少50个SNP的病理分析的基因突变的影响能量学中，我们发现，事实上，一些SNP可别构工作。我们示出了由与人类半乳糖-1-磷酸尿苷酰转移酶（GALT）和葡萄糖-6-磷酸脱氢酶（G6PD）的情况下，研究的SNP变构疾病表型的分子基础。我们还发现，一些蛋白质中的其它残基的突变可导致调制比得上那些已知病理的SNP观察。为了说明这一点，我们提出变构多态性，这意味着许多蛋白质序列，其突变可别构破坏的疾病表型的蛋白质的作用和效果的关键位置存在的概念。我们的结论是变构多态性的新兴重要性计算框架的发展分析突变的变构效应及其在蛋白质活性的调节作用调用。 （c）2019 Elsevier Ltd.保留所有权利。

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