通过量子力学/分子力学自由能混合计算揭示 BLUF 感光蛋白的光激活机制

IF 3.7 Q2 CHEMISTRY, PHYSICAL
Masahiko Taguchi, Shun Sakuraba, Justin Chan and Hidetoshi Kono*, 
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引用次数: 0

摘要

OaPAC 是一种光激活酶,可形成同源二聚体。两个利用蓝光的黄素(BLUF)光感受器结构域与催化结构域之间有长的盘卷 C 端螺旋连接。在感光过程中,Tyr6、Gln48 和 BLUF 结构域中的发色团之间的氢键网络会发生重组,Gln48 也会发生酮烯醇同分异构。然而,光异构化反应的定量能量以及 BLUF 结构域的结构变化如何向催化结构域传播仍是未知数。我们通过自由能扰动计算结合 QM/MM 自由能优化,评估了暗态和两种不同光态结构之间的自由能差异。此外,我们还对经过自由能优化的暗态和亮态结构进行了长时间的 MD 模拟,以阐明光异构化时蛋白质动力学的差异。据估计,两种优化的光态结构之间的自由能差为 4.7 kcal/mol。自由能优化的光态结构表明,光态下化学性质不稳定的 Gln48 烯醇同系物通过与发色团和 Tyr6 形成强氢键网络而得到稳定。此外,暗态和亮态结构之间的自由能差成分表明,光接收时的能量被储存在环境中,而不是内部的光接收区域,这表明存在一种机制,使 Gln48 的化学性质不稳定的烯醇同系物保持光激活信号状态。在光照状态下,C-末端螺旋附近的 Trp90 波动变得很大,从而导致 BLUF 核心和 C-末端螺旋的结构发生变化。我们还确定了在暗态和亮态之间残基接触图存在显著差异的残基对。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Unveiling the Photoactivation Mechanism of BLUF Photoreceptor Protein through Hybrid Quantum Mechanics/Molecular Mechanics Free-Energy Calculation

OaPAC is a photoactivated enzyme that forms a homodimer. The two blue-light using flavin (BLUF) photoreceptor domains are connected to the catalytic domains with long coiled-coil C-terminal helices. Upon photoreception, reorganization of the hydrogen bonding network between Tyr6, Gln48, and the chromophore in the BLUF domain and keto–enol tautomerization of Gln48 are thought to occur. However, the quantitative energetics of the photoisomerization reaction and how the BLUF domain’s structural change propagates toward the catalytic domain are still unknown. We evaluate the free-energy differences among the dark-state and two different light-state structures by the free-energy perturbation calculations combined with QM/MM free-energy optimizations. Furthermore, we performed long-time MD simulations for the free-energetically optimized dark- and light-state structures to clarify the differences in protein dynamics upon photoisomerization. The free-energy difference between the two optimized light-state structures was estimated at ∼4.7 kcal/mol. The free-energetically optimized light-state structure indicates that the chemically unstable enol tautomer of Gln48 in the light state is stabilized by forming a strong hydrogen bonding network with the chromophore and Tyr6. In addition, the components of free-energy difference between the dark- and light-state structures show that the energy upon photoreception is stored in the environment rather than the internal photoreceived region, suggesting a mechanism to keep the photoactivated signaling state with the chemically unstable enol tautomer of Gln48. In the light state, a fluctuation of Trp90 near the C-terminal helix becomes large, which causes subsequent structural changes in the BLUF core and the C-terminal helix. We also identified residue pairs with significant differences concerning residue-wise contact maps between the dark and light states.

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来源期刊
CiteScore
3.70
自引率
0.00%
发文量
0
期刊介绍: ACS Physical Chemistry Au is an open access journal which publishes original fundamental and applied research on all aspects of physical chemistry. The journal publishes new and original experimental computational and theoretical research of interest to physical chemists biophysical chemists chemical physicists physicists material scientists and engineers. An essential criterion for acceptance is that the manuscript provides new physical insight or develops new tools and methods of general interest. Some major topical areas include:Molecules Clusters and Aerosols; Biophysics Biomaterials Liquids and Soft Matter; Energy Materials and Catalysis
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