Neutral Histidine and Photoinduced Electron Transfer in DNA Photolyases
Neutral Histidine and Photoinduced Electron Transfer in DNA Photolyases
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DOI：
10.1021/ja203964d
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发表时间：
2011-11-16
影响因子：
15
通讯作者：
Domratcheva, Tatiana
中科院分区：
文献类型：
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作者：
Domratcheva, Tatiana
紫外线引起的两种主要的DNA损伤，环丁烷嘧啶二聚体（CPD）和（6-4）嘧啶-嘧啶酮光产物，可以分别被光激活酶CPD和（6-4）光解酶修复。这是一个长期存在的问题，这两类具有相似分子结构的光解酶如何能够逆转两种化学性质不同的DNA光产物。在这两种光解酶中，修复反应都是通过光诱导电子从黄素腺嘌呤二核苷酸（FADH（-））辅因子的氢醌阴离子部分转移到光产物而启动的。在这里，采用最先进的XMCQDPT 2-CASSCF方法来计算各个活性位点模型的激发光谱。结果表明，在氢醌-阴离子电子供体存在下，His 365的质子化引起自发的，而不是光诱导的，耦合的质子和电子转移到（6-4）光产物。由此产生的中和的双自由基，含有中性半醌和N3 '-质子化的（6-4）光产物中性自由基，对应于最低能量的电子基态最小值。N3 '-质子化的（6-4）光产物的高电子亲和力强调了这一发现。因此，预期（6-4）光产物修复由His 365以其中性形式辅助，这与文献中提出的修复机制相反。考虑了中性His 365辅助下的羟基转移修复。修复涉及（6-4）光产物的5 '碱基自由基阴离子，其在电子结构方面类似于CPD自由基阴离子。提出了CPD和（6-4）光产物修复的统一模型。
The two major UV-induced DNA lesions, the cyclobutane pyrimidine dimers (CPD) and (6-4) pyrimidine-pyrimidone photoproducts, can be repaired by the light-activated enzymes CPD and (6-4) photolyases, respectively. It is a long-standing question how the two classes of photolyases with alike molecular structure are capable of reversing the two chemically different DNA photoproducts. In both photolyases the repair reaction is initiated by photoinduced electron transfer from the hydroquinone-anion part of the flavin adenine dinucleotide (FADH(-)) cofactor to the photoproduct. Here, the state-of-the-art XMCQDPT2-CASSCF approach was employed to compute the excitation spectra of the respective active site models. It is found that protonation of His365 in the presence of the hydroquinone-anion electron donor causes spontaneous, as opposed to photoinduced, coupled proton and electron transfer to the (6-4) photoproduct. The resulting neutralized biradical, containing the neutral semiquinone and the N3'-protonated (6-4) photoproduct neutral radical, corresponds to the lowest energy electronic ground-state minimum. The high electron affinity of the N3'-protonated (6-4) photoproduct underlines this finding. Thus, it is anticipated that the (6-4) photoproduct repair is assisted by His365 in its neutral form, which is in contrast to the repair mechanisms proposed in the literature. The repair via hydroxyl group transfer assisted by neutral His365 is considered. The repair involves the 5'base radical anion of the (6-4) photoproduct which in terms of electronic structure is similar to the CPD radical anion. A unified model of the CPD and (6-4) photoproduct repair is proposed.