Kinetic gating of the proton pump in cytochrome c oxidase.
Kinetic gating of the proton pump in cytochrome c oxidase.
复制标题
细胞色素 c 氧化酶中质子泵的动力学门控。
DOI：
10.1073/pnas.0903938106
复制
发表时间：
2009
影响因子：
11.1
通讯作者：
Hummer,Gerhard
中科院分区：
文献类型：
--
作者：
Kim,YoungC;Wikstrom,Marten;Hummer,Gerhard
Cytochromecoxidase (CcO), the terminal enzyme of the respiratory chain, reduces oxygen to water and uses the released energy to pump protons across a membrane. Here, we use kinetic master equations to explore the energetic and kinetic control of proton pumping in CcO. We construct models consistent with thermodynamic principles, the structure of CcO, experimentally known proton affinities, and equilibrium constants of intermediate reactions. The resulting models are found to capture key properties of CcO, including the midpoint redox potentials of the metal centers and the electron transfer rates. We find that coarse-grained models with two proton sites and one electron site can pump one proton per electron against membrane potentials exceeding 100 mV. The high pumping efficiency of these models requires strong electrostatic couplings between the proton loading (pump) site and the electron site (hemea), and kinetic gating of the internal proton transfer. Gating is achieved by enhancing the rate of proton transfer from the conserved Glu-242 to the pump site on reduction of hemea, consistent with the predictions of the water-gated model of proton pumping. The model also accounts for the phenotype of D-channel mutations associated with loss of pumping but retained turnover. The fundamental mechanism identified here for the efficient conversion of chemical energy into an electrochemical potential should prove relevant also for other molecular machines and novel fuel-cell designs.
