Denis M
Biochimie. 1986 Mar;68(3):459-70. doi: 10.1016/s0300-9084(86)80013-x.
Recent works on the structure and the function of cytochrome-c oxidase are reviewed. The subunit composition of the mitochondrial enzyme depends on the species and is comprised of between 5 and 13 subunits. It is reduced to 1 to 3 subunits in prokaryotes. The complete amino acid composition has been derived from protein sequencing. Gene sequences are partially known in several eukaryote species. Metal centers are only located in subunits I and II. The mitochondrial cytochrome-c oxidase is Y-shaped; the arms of the Y cross the inner membrane, the stalk protrudes into the intermembrane space. The bacterial enzyme has a simpler, elongated shape. A number of data have been accumulated on the subunit topology and on their location within the protein. All available spectrometric techniques have been used to investigate the environment of the metal centers as well as their interactions. From the literature, attention must be paid to what may be considered or not as an active form. The steady improvement of the instrumentation has yielded evidence for different kinds of heterogeneities which could reflect the in vivo situation. The 'pulsed' and 'resting' conformers have been well characterized. The 'oxygenated' form has been identified as a peroxide derivative of the fully oxidized cytochrome-c oxidase. The mammalian enzyme has been isolated in fully active monomeric form which does not preclude the initially suggested dimeric behavior in situ. The role of the lipids is still largely investigated, mainly through reconstitution experiments. Kinetic studies of electron transfer between cytochrome c and cytochrome-c oxidase lead to a single catalytic site model to account for the multiphasic kinetics. Results related to the low temperature investigation of the intermediate steps in the reaction between oxygen and cytochrome-c oxidase received a sound confirmation by the resolution of compound A at room temperature. It is also pointed out that the so-called mixed valence state might not be a transient state in the catalytic reduction of oxygen. The functioning of cytochrome-c oxidase as a proton pump has been supported by a number of experimental results. Subunit III would be involved in this process. The redox link to the proton pump has been suggested to be at the Fea-CuA site. The molecular mechanism responsible for the proton pumping is still unknown.
本文综述了近期关于细胞色素c氧化酶结构与功能的研究工作。线粒体酶的亚基组成因物种而异，由5至13个亚基组成。在原核生物中，其亚基数量减少至1至3个。完整的氨基酸组成已通过蛋白质测序得出。在几种真核生物物种中，基因序列已部分知晓。金属中心仅位于亚基I和II中。线粒体细胞色素c氧化酶呈Y形；Y的臂穿过内膜，柄伸入膜间隙。细菌酶的形状则更为简单，呈细长形。关于亚基拓扑结构及其在蛋白质中的位置，已经积累了大量数据。所有可用的光谱技术都被用于研究金属中心的环境及其相互作用。从文献中可知，必须关注哪些可被视为或不被视为活性形式。仪器设备的不断改进已为不同类型的异质性提供了证据，这些异质性可能反映了体内情况。“脉冲”和“静止”构象已得到充分表征。“氧化态”形式已被鉴定为完全氧化的细胞色素c氧化酶的过氧化物衍生物。哺乳动物的酶已被分离出完全活性的单体形式，但这并不排除最初提出的原位二聚体行为。脂质的作用仍在很大程度上通过重组实验进行研究。细胞色素c与细胞色素c氧化酶之间电子转移的动力学研究导致了一个单一催化位点模型，以解释多相动力学。通过在室温下解析化合物A，与氧和细胞色素c氧化酶反应中间步骤的低温研究相关的结果得到了有力证实。还指出，所谓的混合价态在氧的催化还原过程中可能不是一个瞬态。细胞色素c氧化酶作为质子泵的功能已得到多项实验结果的支持。亚基III可能参与此过程。质子泵的氧化还原联系被认为位于Fea-CuA位点。负责质子泵浦的分子机制仍然未知。
