A histidine residue acting as a controlling site for dioxygen reduction and proton pumping by cytochrome c oxidase
A histidine residue acting as a controlling site for dioxygen reduction and proton pumping by cytochrome c oxidase
复制标题
DOI：
10.1073/pnas.0610031104
复制
发表时间：
2007-05-08
影响因子：
11.1
通讯作者：
Yoshikawa, Shinya
中科院分区：
文献类型：
--
作者：
Muramoto, Kazumasa;Hirata, Kunio;Yoshikawa, Shinya
细胞色素c氧化酶传递电子和质子用于双氧还原，并伴有质子泵送。这些电子和质子的转移相互紧密耦合，通过各种未知的机制进行有效的能量转导。在这里，我们报道了一种偶联机制，即在质子转移途径入口的组氨酸（His-503）到达牛心脏细胞色素c氧化酶的二氧还原位点（d途径）。在还原状态下，水分子被His-503和Asp-91之间的氢键固定，并通过两个延伸到分子表面的水阵列连接。Asp-91的微环境在x射线结构中表现出与His-503一样高的质子亲和力。因此，Asp-91和His-503在固定的水分子上合作捕获从分子表面通过水阵列转移的质子。在氧化过程中，His-503咪唑平面旋转180度，断开与质子化水的氢键，将质子释放给Asp-91。在还原过程中，Asp-91通过d途径将质子提供给二氧还原位点。在x射线结构中，通过抑制Zn2+和Cd2+与His-503结合的部分电子转移，证实了His-503控制的质子收集。陈建军，陈建军，陈建军，等。Zn2+对His-503的x射线结构的K-d估计与Zn2+对His-503的完全质子泵浦抑制的Kd一致[j].光子学报，2001,(3):142-146。这些结果表明His-503将质子转移与质子泵浦耦合在一起。
Cytochrome c oxidase transfers electrons and protons for dioxygen reduction coupled with proton pumping. These electron and proton transfers are tightly coupled with each other for the effective energy transduction by various unknown mechanisms. Here, we report a coupling mechanism by a histidine (His-503) at the entrance of a proton transfer pathway to the dioxygen reduction site (D-pathway) of bovine heart cytochrome c oxidase. In the reduced state, a water molecule is fixed by hydrogen bonds between His-503 and Asp-91 of the D-pathway and is linked via two water arrays extending to the molecular surface. The microenvironment of Asp-91 appears in the x-ray structure to have a proton affinity as high as that of His-503. Thus, Asp-91 and His-503 cooperatively trap, on the fixed water molecule, the proton that is transferred through the water arrays from the molecular surface. On oxidation, the His-503 imidazole plane rotates by 180 degrees to break the hydrogen bond to the protonated water and releases the proton to Asp-91. On reduction, Asp-91 donates the proton to the dioxygen reduction site through the D-pathway. The proton collection controlled by His-503 was confirmed by partial electron transfer inhibition by binding of Zn2+ and Cd2+ to His-503 in the x-ray structures. The estimated K-d for Zn2+ binding to His-503 in the x-ray structure is consistent with the reported Kd for complete proton-pumping inhibition by Zn2+ [Kannt A, Ostermann T, Muller H, Ruitenberg M (2001) FEBS Lett 503:142-146]. These results suggest that His-503 couples the proton transfer for dioxygen reduction with the proton pumping.