Electron tunneling pathways and role of adenine in repair of cyclobutane pyrimidine dimer by DNA photolyase.
Electron tunneling pathways and role of adenine in repair of cyclobutane pyrimidine dimer by DNA photolyase.
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电子隧穿途径和腺嘌呤通过DNA光溶解酶修复环丁烷嘧啶二聚体的作用。
DOI：
10.1021/ja2105009
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发表时间：
2012-05-16
影响因子：
15
通讯作者：
Zhong, Dongping
中科院分区：
文献类型：
--
作者：
Liu, Zheyun;Guo, Xunmin;Tan, Chuang;Li, Jiang;Kao, Ya-Ting;Wang, Lijuan;Sancar, Aziz;Zhong, Dongping
酶中的电子隧穿途径对它们的催化效率至关重要。光裂合酶是一种光酶，它通过电子隧穿将紫外光诱导的环丁烷嘧啶二聚体分裂成两个正常的碱基。在这里，我们报告我们的系统的表征和分析的光引发的三个电子转移过程和环丁烷环分裂以下的整个动态演化过程中的酶修复飞秒分辨率。我们观察了反应物、所有中间体和最终产物的完整动力学，并确定了它们的反应时间尺度。使用（脱氧）尿嘧啶和胸腺嘧啶作为二聚体底物，我们明确地确定了电子隧穿途径的正向电子转移启动修复和最终的电子返回恢复活性辅因子和完成催化光循环。值得注意的是，我们发现，不寻常的弯曲黄素辅因子的腺嘌呤部分是必不可少的介导所有电子转移动力学通过超交换机制，导致时间尺度的微妙平衡。环丁烷环分裂需要几十皮秒，而电子转移动力学都发生在一个较长的时间尺度。活性位点的结构完整性，独特的电子隧穿途径和腺嘌呤的关键作用，确保这些基本步骤在这个复杂的光修复机制的协同作用，以实现最大的修复效率，这是接近统一。最后，我们使用Marcus电子转移理论来评估所有三个电子转移过程，从而获得它们的反应驱动力（自由能），重组能，和电子耦合常数，得出正向和无效的背电子转移在正常区域，并在催化循环的最终电子返回是在反转区域。
Electron tunneling pathways in enzymes are critical to their catalytic efficiency. Through electron tunneling, photolyase, a photoenzyme, splits UV-induced cyclobutane pyrimidine dimer into two normal bases. Here, we report our systematic characterization and analyses of photo-initiated three electron transfer processes and cyclobutane ring splitting by following the entire dynamical evolution during enzymatic repair with femtosecond resolution. We observed the complete dynamics of the reactants, all intermediates and final products, and determined their reaction time scales. Using (deoxy)uracil and thymine as dimer substrates, we unambiguously determined the electron tunneling pathways for the forward electron transfer to initiate repair and for the final electron return to restore the active cofactor and complete the catalytic photocycle. Significantly, we found that the adenine moiety of the unusual bent flavin cofactor is essential to mediating all electron-transfer dynamics through a super-exchange mechanism, leading to a delicate balance of time scales. The cyclobutane ring splitting takes tens of picoseconds while electron-transfer dynamics all occur on a longer time scale. The active-site structural integrity, unique electron tunneling pathways and the critical role of adenine assure the synergy of these elementary steps in this complex photorepair machinery to achieve maximum repair efficiency which is close to unity. Finally, we used the Marcus electron-transfer theory to evaluate all three electron transfer processes and thus obtained their reaction driving forces (free energies), reorganization energies, and electronic coupling constants, concluding the forward and futile back electron transfer in the normal region and that the final electron return of the catalytic cycle is in the inverted region.
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影响因子：
3.2
作者：
Boussicault, F;Kr端ger, O;Wille, U
通讯作者：
Wille, U
影响因子：
15
作者：
Chang, Chih-Wei;He, Ting-Fang;Guo, Lijun;Stevens, Jeffrey A.;Li, Tanping;Wang, Lijuan;Zhong, Dongping
通讯作者：
Zhong, Dongping
影响因子：
11.4
作者：
Kiontke, Stephan;Geisselbrecht, Yann;Essen, Lars-Oliver
通讯作者：
Essen, Lars-Oliver
影响因子：
15
作者：
Boggio-Pasqua, Martial;Groenhof, Gerrit;Robb, Michael A.
通讯作者：
Robb, Michael A.
影响因子：
15
作者：
Kao, Ya-Ting;Tan, Chuang;Zhong, Dongping
通讯作者：
Zhong, Dongping