DNA硫修饰的结构与功能
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- 英文论文题名：Structural Features of S-DNA
- 论文作者：赵一雷
- 英文论文作者：Yi-Lei Zhao ; College of Life Sciences and Biotechnology ; Shanghai Jiao Tong University ; State Key Laboratory of Microbial Metabolism ; Joint International Research Laboratory of Metabolic & Developmental Sciences
- 年：2016
- 作者机构：上海交通大学生命科学技术学院;微生物代谢国家重点实验室;
- 论文关键词：DNA ; 硫修饰 ; 结构
- 会议召开时间：2016-07-01
- 会议录名称：中国化学会第30届学术年会摘要集-第二十八分会：化学生物学
- 语种：中文
- 分类号：O629.74
- 学会代码：ZGHY
- 会议名称：中国化学会第30届学术年会-第二十八分会 ; 化学生物学
- 会议地点：中国辽宁大连
- 主办单位：中国化学会
- 学会名称：中国化学会
- 页数：2
- 文件大小：181k
- 原文格式：D
- 会议级别：全国
摘要
DNA硫修饰是一种新型表观化学修饰,细菌基因组分析表明有5-8个基因形成一个硫修饰功能基因簇,把硫原子从半胱氨酸转移到DNA上替换非桥键氧。细菌生物学研究发现其有可能与细菌防御外来基因入侵有关,也有可能与抵抗氧化损失有关。我们通过结构生物信息学研究了硫修饰R立体手性对DNA的高级结构的影响、与周边碱基对发生物理化学互作。首先我们利用量子化学计算比较了修饰之前后的局部结构变化,并构建能量打分函数挖掘正常和硫修饰DNA的磷酸骨架二面角分布差异,进一步通过分子动力学模拟研究不同碱基序列的DNA磷酸骨架柔性变化,从而揭示碱基对、碱基阶梯的特征结构参数细微差异。理论计算发现了R型DNA硫修饰能够干扰DNA的B型双螺旋结构的稳定性,与S-DNA的熔点实验结果相吻合。硫修饰提高了DNA骨架的刚性,与正常DNA相比,骨架与碱基的相互作用变强而提高了碱基序列特异性,特别是与含鸟嘌呤碱基对阶梯互作,表明了DNA硫修饰结构与其分子识别和抗氧化性有直接关系。
DNA phosphorothioation is a novel type of chemical modification in bacterial genomes,where 5-8 genes form a functional cluster and transfer sulfur atom of cysteine to replace non-bridging oxygen of DNA phosphate.It may be related to defense system of bacteria from invasion of alien genes,and from oxidative stress.We carried out comparative quantum calculation on the backbone local conformation and constructed a scoring function to distinguish normal and PT-modified DNA.Then molecular dynamics simulations were conducted,and the structural parameters of local base-pair and base-step were calculated.Our calculations show that B-type helical structure is disturbed by the chiral modification significantly,in agreement with the recently melting experiment.Phosphorothioation also enhances DNA backbone rigidity and thereby promotes base effect,in particular for guanine-involving base pair and base step.The results indicate that specific features in S-DNA structure can directly relate to molecular recognition and antioxidant activity.
DNA phosphorothioation is a novel type of chemical modification in bacterial genomes,where 5-8 genes form a functional cluster and transfer sulfur atom of cysteine to replace non-bridging oxygen of DNA phosphate.It may be related to defense system of bacteria from invasion of alien genes,and from oxidative stress.We carried out comparative quantum calculation on the backbone local conformation and constructed a scoring function to distinguish normal and PT-modified DNA.Then molecular dynamics simulations were conducted,and the structural parameters of local base-pair and base-step were calculated.Our calculations show that B-type helical structure is disturbed by the chiral modification significantly,in agreement with the recently melting experiment.Phosphorothioation also enhances DNA backbone rigidity and thereby promotes base effect,in particular for guanine-involving base pair and base step.The results indicate that specific features in S-DNA structure can directly relate to molecular recognition and antioxidant activity.
引文
[1]Chen,L.-M.;Zhao,Y.-L.*et al J.Phys.Chem.B,2015,119:474.
[2]Zhang,Y.-C.;Zhao,Y.-L.*et al J.Phys.Chem.B,2012,116:10639.
[2]Zhang,Y.-C.;Zhao,Y.-L.*et al J.Phys.Chem.B,2012,116:10639.