Photoinduced Electron Transfer Facilitates Tautomerization of the Conserved Signaling Glutamine Side Chain in BLUF Protein Light Sensors
Photoinduced Electron Transfer Facilitates Tautomerization of the Conserved Signaling Glutamine Side Chain in BLUF Protein Light Sensors
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DOI：
10.1021/jp312775x
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发表时间：
2013-02-28
影响因子：
3.3
通讯作者：
Domratcheva, T.
中科院分区：
文献类型：
--
作者：
Khrenova, M. G.;Nemukhin, A. V.;Domratcheva, T.
来自细菌光感受器蛋白AppA的BLUF结构域（使用黄素腺嘌呤二核苷酸的蓝光传感器）响应于光照射而经历化学转化的级联，包括黄素腺嘌呤二核苷酸（FAD）发色团周围的氢键重排。这些转变是由光诱导的电子和质子转移从酪氨酸残基的光激发黄素，这是由谷氨酰胺残基的协助。根据最近的研究，质子耦合电子转移导致自由基对中间体Tyr中心点的形成。FADH中心点和谷氨酰胺的互变异构EE形式在基态电子状态。该中间体是涉及生物信号传导的BLUF光感受器的光诱导状态的前体。为了描述的自由基对的演变，我们计算的反应途径的基态势能面上采用量子化学计算的DFT PBE 0/cc-pVDZ近似的分子簇模拟的生色团包含口袋的AppA蓝蛋白。我们发现了一个最小能量途径，该途径由以下连续反应步骤组成：（1）EE谷氨酰胺侧链的immunogram基团围绕C γ-C δ键旋转;（2）O-OH基团翻转并形成ZE形式的谷氨酰胺侧链;（3）通过耦合质子和电子转移进行双自由基重组，导致ZZ形式的谷氨酰胺侧链。阶段1-3的势能势垒不超过9千卡/摩尔。BLUF模型中描述ZE至ZZ谷氨酰胺互变异构的能垒3明显小于分离的谷氨酰胺，因为BLUF中的互变异构是由电子转移和自由基重组促进的。因此，我们的研究表明，保守的谷氨酰胺的互变异构耦合到光诱导的电子转移过程中的BLUF，因此，是一个可行的候选人的光活化机制，目前是非常有争议的。
The BLUF domain (sensor of blue light using flavin adenine dinucleotide) from a bacterial photoreceptor protein AppA undergoes a cascade of chemical transformations, including hydrogen bond rearrangements around the flavin adenine dinucleotide (FAD) chromophore, in response to light illumination. These transformations are initiated by photoinduced electron and proton transfer from a tyrosine residue to the photoexcited flavin which is assisted by a glutamine residue. According to the recent studies, the proton-coupled electron transfer leads to formation of a radical-pair intermediate Tyr center dot...FADH center dot and a tautomeric EE form of glutamine in the ground electronic state. This intermediate is a precursor of the light induced state of the BLUF photoreceptor implicated in biological signaling. In order to describe evolution of the radical pair, we computed reaction pathways on the ground state potential energy surface employing quantum-chemical calculations in the DFT PBE0/cc-pVDZ approximation for a molecular cluster mimicking the chromophore containing pocket of the AppA BLUE protein. We found a minimum-energy pathway comprised of the following consecutive reaction steps: (1) rotation of the imidic group of the EE glutamine side chain around the C gamma-C delta bond; (2) flip of the O epsilon H group and formation of the ZE form of the glutamine side chain; and (3) biradical recombination via coupled proton and electron transfer, leading to the ZZ form of the glutamine side chain. The potential-energy barriers for stages 1-3 do not exceed 9 kcal/mol. Energy barrier 3 describing the ZE to ZZ glutamine tautomerization is significantly smaller in the BLUF model than in isolated glutamine, since tautomerization in BLUF is facilitated by electron transfer and radical recombination. Thus, our study shows that tautomerization of the conserved glutamine is coupled to the light-induced electron transfer process in BLUF and, thus, is a viable candidate for the photoactivation mechanism which at present is very much debated.