Terminal Electron-Proton Transfer Dynamics in the Quinone Reduction of Respiratory Complex I.
Terminal Electron-Proton Transfer Dynamics in the Quinone Reduction of Respiratory Complex I.
复制标题
DOI：
10.1021/jacs.7b08486
复制
发表时间：
2017-11-15
影响因子：
15
通讯作者：
Kaila VRI
中科院分区：
文献类型：
--
作者：
Gamiz-Hernandez AP;Jussupow A;Johansson MP;Kaila VRI
复合物I在有氧呼吸链中作为氧化还原驱动的质子泵发挥作用。通过还原醌（Q），复合物I利用在该过程中释放的自由能以化学方式驱动质子泵送穿过其膜结构域。初始Q降低步骤在激活质子泵送机制中起着核心作用。为了探索能量，动力学和分子机制的质子耦合电子转移过程中的Q减少，我们在这里采用多尺度量子和经典分子模拟。我们确定，泛醌（UQ）和甲基萘醌（MQ）可以形成堆叠和氢键相互作用与保守的Q-结合位点残基His-38和这些结合模式之间的构象变化调节Q氧化还原电位和电子转移率（eT）从终端N2铁硫中心。我们进一步观察到，虽然semiquinone的瞬时形成不是质子偶联的，但第二个eT过程偶联到活性位点内保守的酪氨酸（Tyr-87）和组氨酸（His-38）残基的质子摄取。我们的计算表明，UQ和MQ在Q结合位点分别具有约为−260和−230 mV的低氧化还原电位，这表明Q向膜的释放与能量转导步骤相耦合，该能量转导步骤可以在复合物I中间接驱动质子泵。
Complex I functions as a redox-driven proton pump in aerobic respiratory chains. By reducing quinone (Q), complex I employs the free energy released in the process to thermodynamically drive proton pumping across its membrane domain. The initial Q reduction step plays a central role in activating the proton pumping machinery. In order to probe the energetics, dynamics, and molecular mechanism for the proton-coupled electron transfer process linked to the Q reduction, we employ here multiscale quantum and classical molecular simulations. We identify that both ubiquinone (UQ) and menaquinone (MQ) can form stacking and hydrogen-bonded interactions with the conserved Q-binding-site residue His-38 and that conformational changes between these binding modes modulate the Q redox potentials and the rate of electron transfer (eT) from the terminal N2 iron–sulfur center. We further observe that, while the transient formation of semiquinone is not proton-coupled, the second eT process couples to a semiconcerted proton uptake from conserved tyrosine (Tyr-87) and histidine (His-38) residues within the active site. Our calculations indicate that both UQ and MQ have low redox potentials around −260 and −230 mV, respectively, in the Q-binding site, respectively, suggesting that release of the Q toward the membrane is coupled to an energy transduction step that could thermodynamically drive proton pumping in complex I.
登录
查看更多内容
影响因子：
64.8
作者：
Fiedorczuk, Karol;Letts, James A.;Degliesposti, Gianluca;Kaszuba, Karol;Skehel, Mark;Sazanov, Leonid A.
通讯作者：
Sazanov, Leonid A.
DOI：
10.1039/p29930000799
发表时间：
1993-05-01
期刊：
JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 2
影响因子：
--
作者：
KLAMT, A;SCHUURMANN, G
通讯作者：
SCHUURMANN, G
影响因子：
3
作者：
Galstyan, Artur;Knapp, Ernst-Walter
通讯作者：
Knapp, Ernst-Walter
影响因子：
2.9
作者：
Hanley, J;Deligiannakis, Y;Rutherford, AW
通讯作者：
Rutherford, AW
影响因子：
4.4
作者：
BECKE, AD
通讯作者：
BECKE, AD