Siegbahn Per E M, Blomberg Margareta R A
Department of Physics, Albanova, SE-106 91, Stockholm, Sweden.
J Phys Chem A. 2008 Dec 18;112(50):12772-80. doi: 10.1021/jp801635c.
Two different issues, important for the pumping mechanism of cyctochrome c oxidase, have been addressed in the present study. One of them concerns the nature of two key proton transfer transition states. A simple electrostatic model is used to suggest that the transition state (TS) for transfer to the pump-site should be positively charged, while the one for transfer to the binuclear center should be charge-neutral. The character of the former TS will guarantee that the protons will be pumped to the outside and not return to the inside, while the neutral character of the latter one will allow transfer with a sufficiently low barrier. In the simple electrostatic analysis, leading to this qualitative picture of the pumping process, the results from the kinetic experiments are strictly followed, but it is at least as important to follow the fundamental requirements for pumping. In this perspective, the uncertainties in the quantitative analysis should be rather unimportant for the emerging qualitative picture of the pumping mechanism. The second problem addressed concerns the purpose of the K-channel. It is argued that the reason for the presence of the K-channel could be that protons cannot pass through the binuclear center at some stage of pumping. Barriers and water binding energies were computed using hybrid density functional theory (DFT) to investigate this question.
本研究探讨了两个对细胞色素c氧化酶泵浦机制很重要的不同问题。其中一个涉及两个关键质子转移过渡态的性质。使用一个简单的静电模型表明，转移到泵浦位点的过渡态（TS）应带正电荷，而转移到双核中心的过渡态应呈电荷中性。前一个TS的性质将确保质子被泵浦到外部而不会回到内部，而后一个的中性性质将允许以足够低的势垒进行转移。在导致泵浦过程这种定性描述的简单静电分析中，严格遵循了动力学实验的结果，但遵循泵浦的基本要求至少同样重要。从这个角度来看，定量分析中的不确定性对于泵浦机制新出现的定性描述应该不太重要。所探讨的第二个问题涉及K通道的目的。有人认为，K通道存在的原因可能是在泵浦的某个阶段质子无法通过双核中心。使用混合密度泛函理论（DFT）计算了势垒和水结合能来研究这个问题。
