Department of Organic Chemistry, Arrhenius Laboratory, Stockholm University, SE-106 91 Stockholm, Sweden.
J Inorg Biochem. 2020 May;206:111020. doi: 10.1016/j.jinorgbio.2020.111020. Epub 2020 Feb 8.
Cytochrome c oxidase (CcO), the terminal enzyme in the respiratory chain, reduces molecular oxygen to water. Experimental data on the midpoint potentials of the heme iron/copper active site cofactors do not match the overall reaction energetics, and are also in conflict with the observed efficiency of energy conservation in CcO. Therefore it has been postulated that the ferric/cupric intermediate (the oxidized state) exists in two forms. One form, labelled O, is presumably involved during catalytic turnover, and should have a high Cu midpoint potential due to a metastable high energy structure. When no more electrons are supplied, the O state supposedly relaxes to the resting form, labelled O, with a lower energy and a lower midpoint potential. It has been suggested that there is a pure geometrical difference between the O and O states, obtained by moving a water molecule inside the active site. It is shown here that the difference between the two forms of the oxidized state must be of a more chemical nature. The reason is that all types of geometrically relaxed structures of the oxidized intermediate have similar energies, all with a high proton coupled reduction potential in accordance with the postulated O state. One hypothesized chemical modification of the O state is the transfer of an extra proton, possibly internal, into the active site. Such a protonated state has several properties that agree with experimental data on the relaxed oxidized state, including a decreased midpoint potential.
细胞色素 c 氧化酶（CcO）是呼吸链中的末端酶，将分子氧还原为水。血红素铁/铜活性位点辅因子的中间点电势的实验数据与整体反应能量学不匹配，也与 CcO 中观察到的能量守恒效率相冲突。因此，有人假设高铁/铜中间态（氧化态）存在两种形式。一种形式，标记为 O，据推测在催化周转期间参与，由于亚稳态高能结构，其铜中间点电势应该很高。当不再提供电子时，O 态据称会松弛到具有较低能量和较低中间点电势的静止形式 O。有人认为，O 和 O 态之间存在纯几何差异，可以通过在活性位点内移动一个水分子来获得。这里表明，氧化态两种形式之间的差异必须具有更化学的性质。原因是氧化中间态的所有类型的几何松弛结构都具有相似的能量，所有结构都具有与假设的 O 态一致的高质子偶联还原电势。O 态的一种假设的化学修饰是将额外的质子（可能是内部的）转移到活性位点中。这样的质子化状态具有几个与松弛氧化态的实验数据相符的性质，包括中间点电势降低。
