Exploring the possible role of Glu286 in CcO by electrostatic energy computations combined with molecular dynamics.
Exploring the possible role of Glu286 in CcO by electrostatic energy computations combined with molecular dynamics.
复制标题
通过静电能计算结合分子动力学探索Glu286在CcO中可能的作用
DOI：
10.1021/jp407250d
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
E.W. Knapp
中科院分区：
文献类型：
--
作者：
A.L. Woelke;G. Galstyan;A. Galstyan;T. Meyer;J. Heberle;E.W. Knapp
细胞色素氧化酶（Cytochromecoxidase，CcO）是有氧生物中的一种重要酶，催化氧分子转化为水，并利用化学能泵送质子，建立电化学梯度。尽管进行了深入的研究，但尚不清楚CcO如何实现单向质子传输并避免质子泵短路。在这项工作中，我们分析了Glu 286作为质子阀的潜在作用。我们进行了无约束的MD模拟CcO与明确的膜高达80 ns。这些MD模拟揭示了去质子化的Glu 286（Glu 286-）被血红素a3的带负电荷的丙酸PRD排斥。因此，它使连接Glu 286与PRD和双核中心（BNC）的疏水腔中潜在的线性沃茨链不稳定。相反，质子化的Glu 286（Glu 286 H）可以保持在向上的位置（朝向PRD），并且可以稳定疏水腔中的连接线性水链。我们计算出Glu 286在生理条件下的pKa大于12，但在Glu 286的水可及性增加的情况下，该值降低到约9。后者的值是根据实验测量。在MD模拟的时间过程中，我们还观察到Glu 286桥接位于两侧的水分子（D通道连接到N侧和疏水腔）的构象，这可能导致质子回流。
Cytochromecoxidase (CcO) is a central enzyme in aerobic life catalyzing the conversion of molecular oxygen to water and utilizing the chemical energy to pump protons and establish an electrochemical gradient. Despite intense research, it is not understood how CcO achieves unidirectional proton transport and avoids short circuiting the proton pump. Within this work, we analyzed the potential role of Glu286 as a proton valve. We performed unconstrained MD simulations of CcO with an explicit membrane for up to 80 ns. Those MD simulations revealed that deprotonated Glu286 (Glu286-) is repelled by the negatively charged propionic acid PRD of heme a3. Thus, it destabilizes a potential linear chain of waters in the hydrophobic cavity connecting Glu286 with PRD and the binuclear center (BNC). Conversely, protonated Glu286 (Glu286H) may remain in an upward position (oriented toward PRD) and can stabilize the connecting linear water chain in the hydrophobic cavity. We calculated the pKaof Glu286 under physiological conditions to be above 12, but this value decreases to about 9 under increased water accessibility of Glu286. The latter value is in accordance with experimental measurements. In the time course of MD simulation, we also observed conformations where Glu286 bridges between water molecules located on both sides (the D channel being connected to the N side and the hydrophobic cavity), which might lead to proton backflow.
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影响因子：
3.3
作者：
Klauda, Jeffery B.;Venable, Richard M.;Freites, J. Alfredo;O'Connor, Joseph W.;Tobias, Douglas J.;Mondragon-Ramirez, Carlos;Vorobyov, Igor;MacKerell, Alexander D., Jr.;Pastor, Richard W.
通讯作者：
Pastor, Richard W.
影响因子：
4.3
作者：
Koepke, Juergen;Olkhova, Elena;Michel, Hartmut
通讯作者：
Michel, Hartmut
影响因子：
4.8
作者：
Kieseritzky, Gernot;Knapp, Ernst-Walter
通讯作者：
Knapp, Ernst-Walter
Glu-286 旋转和水线重新定向不太可能是细胞色素 C 氧化酶中质子泵送的门控元件。
影响因子：
3.4
作者：
Shuo Yang;Q. Cui
通讯作者：
Q. Cui
细胞色素 c 氧化酶中谷氨酸 242 侧链的动力学。
DOI：
--
发表时间：
2007
期刊：
Biochimica et Biophysica Acta
影响因子：
--
作者：
A. Tuukkanen;Ville R. I. Kaila;L. Laakkonen;G. Hummer;M. Wikström
通讯作者：
M. Wikström