Gao Yi Qin, Yang Wei, Karplus Martin
Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
Cell. 2005 Oct 21;123(2):195-205. doi: 10.1016/j.cell.2005.10.001.
Many essential functions of living cells are performed by nanoscale protein motors. The best characterized of these is F(o)F1-ATP synthase, the smallest rotary motor. This rotary motor catalyzes the synthesis of ATP with high efficiency under conditions where the reactants (ADP, H2PO4(-)) and the product (ATP) are present in the cell at similar concentrations. We present a detailed structure-based kinetic model for the mechanism of action of F1-ATPase and demonstrate the role of different protein conformations for substrate binding during ATP synthesis and ATP hydrolysis. The model shows that the pathway for ATP hydrolysis is not simply the pathway for ATP synthesis in reverse. The findings of the model also explain why the cellular concentration of ATP does not inhibit ATP synthesis.
活细胞的许多基本功能是由纳米级蛋白质马达执行的。其中最具特征的是F(o)F1-ATP合酶，即最小的旋转马达。这种旋转马达在反应物（ADP、H2PO4(-)）和产物（ATP）在细胞中以相似浓度存在的条件下高效催化ATP的合成。我们提出了一个基于结构的详细动力学模型，用于描述F1-ATP酶的作用机制，并证明了不同蛋白质构象在ATP合成和ATP水解过程中对底物结合的作用。该模型表明，ATP水解的途径并非简单地是ATP合成途径的反向。该模型的研究结果还解释了为什么细胞内ATP的浓度不会抑制ATP的合成。
