Insights into conformational changes in AlkD bound to DNA with a yatakemycin adduct from computational simulations
Insights into conformational changes in AlkD bound to DNA with a yatakemycin adduct from computational simulations
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通过计算模拟深入了解 AlkD 与 yatakemycin 加合物结合到 DNA 时的构象变化
DOI：
10.1007/s00214-018-2255-7
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发表时间：
2018
影响因子：
1.7
通讯作者：
G. A. Cisneros
中科院分区：
文献类型：
--
作者：
P. Silvestrov;G. A. Cisneros
DNA分子的结构完整性是其信息存储功能所必需的。细胞依赖于许多途径来确保由内源性和外源性试剂诱导的DNA损伤得到修复。AlkD是一种碱基切除酶，通过切割糖苷键来去除受损的核碱基。与许多其他碱基切除酶不同，AlkD不会将受损的核碱基翻转到指定的反应口袋中，因此可以用更大的加合物修复核碱基，如Yatakemycin。在这项研究中，AlkD的结构和动力学进行了研究，通过经典的分子动力学模拟。几个系统，包括apo-AlkD，和AlkD与DNA的复合物，有和没有的矢田霉素加合物进行了模拟。apo-AlkD与具有底物（受损或未受损）的AlkD的结果的比较表明apo-AlkD中螺旋αB的高度运动，而当底物结合时，观察到该螺旋形成各种接触。计算结果与以前的实验研究表明，参与损伤识别，DNA结合，和碱基切除催化的各种残基是一致的。
Structural integrity of DNA molecules is necessary for their information storage function. Cells rely on a number of pathways to ensure that the damage to DNA induced by endogenous and exogenous reagents is repaired. AlkD, a base excision enzyme, removes a damaged nucleobase by cleaving a glycosidic bond. Unlike many other base excision enzymes, AlkD does not flip a damaged nucleobase into a designated reaction pocket, and as such can repair nucleobases with larger adducts, such as yatakemycin. In this study, the structure and dynamics of AlkD have been investigated by classical molecular dynamics simulations. Several systems including apo-AlkD, and AlkD in complex with DNA, both with and without the yatakemycin adduct have been simulated. Comparison of the results for the apo-AlkD with AlkD with substrate (damaged or undamaged) indicates a high degree of motion of helix αB in apo-AlkD, whereas this helix is observed to form various contacts when the substrate is bound. The calculated results are consistent with previous experimental studies that have suggested various residues involved in damage recognition, DNA binding, and base excision catalysis.
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影响因子：
5.5
作者：
Contreras-Garcia, Julia;Johnson, Erin R.;Keinan, Shahar;Chaudret, Robin;Piquemal, Jean-Philip;Beratan, David N.;Yang, Weitao
通讯作者：
Yang, Weitao
DOI：
10.1016/j.bbapap.2012.10.005
发表时间：
2013-01
影响因子：
3.2
作者：
Brooks, Sonja C.;Adhikary, Suraj;Rubinson, Emily H.;Eichman, Brandt F.
通讯作者：
Eichman, Brandt F.
影响因子：
15
作者：
Parrish, JP;Kastrinsky, DB;Boger, DL
通讯作者：
Boger, DL
影响因子：
15
作者：
Johnson ER;Keinan S;Mori-Sánchez P;Contreras-García J;Cohen AJ;Yang W
通讯作者：
Yang W
影响因子：
3.8
作者：
Mullins, Elwood A.;Rubinson, Emily H.;Eichman, Brandt F.
通讯作者：
Eichman, Brandt F.