Insights into the mechanism of proton transport in cytochrome c oxidase.
Insights into the mechanism of proton transport in cytochrome c oxidase.
复制标题
深入了解细胞色素 C 氧化酶中的质子运输机制。
DOI：
10.1021/ja209176e
复制
发表时间：
2012
影响因子：
15
通讯作者：
Voth,GregoryA
中科院分区：
文献类型：
--
作者：
Yamashita,Takefumi;Voth,GregoryA
细胞色素氧化酶(CcO)被称为电子传递链的复合体IV，在细胞的有氧呼吸中发挥着重要作用。电子从细胞色素膜转移到CcO的催化位置，还原分子氧，生成水分子。这些电子转移也驱动活跃的质子从线粒体的基质(N侧)泵到膜间区(P侧)；由此产生的质子梯度激活ATP合成酶从ADP合成ATP。虽然在实验上证实了电子转移和质子转移(PT)之间存在耦合，但其机制在分子水平上还没有完全被理解。在这项工作中，它表明了为什么减少血红素a对于质子泵浦是必不可少的。通过新颖的反应分子动力学(MD)模拟证明了这一点，该模拟可以描述与PT相关的格罗特苏斯穿梭以及过剩质子电子电荷缺陷的动态离域。此外，首次明确地证明了Glu242残基(牛CcO记法)的“阀门”作用和血红素A3的d-丙酸(PRDa3)在显性PT中的门作用。这些结果为实验推断的CcO质子输运机制提供了确凿的证据，同时也加深了对CcO质子开关的分子水平的了解。
Cytochromecoxidase (CcO), known as complex IV of the electron transport chain, plays several important roles in aerobic cellular respiration. Electrons transferred from cytochromecto CcO’s catalytic site reduce molecular oxygen and produce a water molecule. These electron transfers also drive active proton pumping from the matrix (N-side) to intermembrane region (P-side) in mitochondria; the resultant proton gradient activates ATP synthase to produce ATP from ADP. Although the existence of the coupling between the electron transfer and the proton transport (PT) is established experimentally, its mechanism is not yet fully understood at the molecular level. In this work, it is shown why the reduction of heme a is essential for proton pumping. This is demonstrated via novel reactive molecular dynamics (MD) simulations that can describe the Grotthuss shuttling associated with the PT as well as the dynamic delocalization of the excess proton electronic charge defect. Moreover, the “valve” role of the Glu242 residue (bovine CcO notation) and the gate role ofd-propionate of heme a3(PRDa3) in the explicit PT are explicitly demonstrated for the first time. These results provide conclusive evidence for the CcO proton transporting mechanism inferred from experiments, while deepening the molecular level understanding of the CcO proton switch.
通过使用磷酸酪氨酸抗体筛选表达文库来鉴定编码蛋白酪氨酸激酶的 cDNA 克隆。
影响因子：
8
作者：
Lindberg,RA;Thompson,DP;Hunter,T
通讯作者：
Hunter,T
利用磷酸酪氨酸抗血清鉴定 v-src、v-yes、v-fps、v-ros 和 v-erb-B 致癌酪氨酸蛋白激酶的多种新型多肽底物。
影响因子：
8
作者：
Kamps,MP;Sefton,BM
通讯作者：
Sefton,BM
通过 cDNA 文库的磷酸酪氨酸抗体筛选鉴定出新型酪氨酸激酶。
影响因子：
5.3
作者：
Kornbluth,S;Paulson,KE;Hanafusa,H
通讯作者：
Hanafusa,H