Theoretical study of excitation energy transfer in DNA photolyase.
Theoretical study of excitation energy transfer in DNA photolyase.
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DNA光裂合酶激发能量转移的理论研究。
DOI：
10.1021/jp800053a
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发表时间：
2008
期刊：
影响因子：
--
通讯作者：
Stuchebrukhov,AlexeiA
中科院分区：
文献类型：
--
作者：
Zheng,Xuehe;Garcia,Jorge;Stuchebrukhov,AlexeiA
光解酶是一种DNA修复酶，它通过光激活的FADH辅助因子与−/PL复合体中的DNA二聚体发生电子转移反应，使紫外光诱导的胸腺嘧啶二聚体裂解。对尼杜兰鱼腥藻DNA/光解酶复合体的晶体结构进行了解析。在这里，利用实验的晶体结构，我们重新检查了修复电子转移反应的细节，并解决了从天线HDF到氧化还原活性FADH−辅因子的能量转移问题。FADH−在电子转移之前的光活化是修复机制中的关键步骤，在很大程度上没有得到理论上的检验。在从头计算中发现了黄素的一个重要的蝴蝶热运动；我们提出了它在从DNA到光解酶的背电子转移中的作用。对整个蛋白质/脱氧核糖核酸复合体进行了分子动力学模拟，得到了相应的辅因子构象，用于ZINDO/S的光谱吸收和荧光计算。我们发现，由于蛋白质动力学导致的谱线显著的热展宽，以及供体HDF和受体FADH−跃迁偶极矩的对准，都有助于能量转移的效率。计算出FöRster偶极耦合的几何因子为1.82，比实验估计的0.6 7有很大提高。利用FöRster机理，我们发现能量转移发生的效率非常显著，与实验值98%相当。
Photolyase (PL) is a DNA repair enzyme which splits UV light-induced thymine dimers on DNA by an electron transfer reaction occurring between the photoactivated FADH−cofactor and the DNA dimer in the DNA/PL complex. The crystal structure of the DNA/photolyase complex fromAnacystis nidulanshas been solved. Here, using the experimental crystal structure, we re-examine the details of the repair electron transfer reaction and address the question of energy transfer from the antenna HDF to the redox active FADH−cofactor. The photoactivation of FADH−immediately preceding the electron transfer is a key step in the repair mechanism that is largely left unexamined theoretically. An important butterfly thermal motion of flavin is identified in ab initio calculations; we propose its role in the back electron transfer from DNA to photolyase. Molecular dynamics simulation of the whole protein/DNA complex is carried out to obtain relevant cofactor conformations for ZINDO/S spectroscopic absorption and fluorescence calculations. We find that significant thermal broadening of the spectral lines, due to protein dynamics, as well as the alignment of the donor HDF and the acceptor FADH−transition dipole moments both contribute to the efficiency of energy transfer. The geometric factor of Förster’s dipolar coupling is calculated to be 1.82, a large increase from the experimentally estimated 0.67. Using Förster’s mechanism, we find that the energy transfer occurs with remarkable efficiency, comparable with the experimentally determined value of 98%.