The Structure and Catalytic Cycle of a Sodium-Pumping Pyrophosphatase
The Structure and Catalytic Cycle of a Sodium-Pumping Pyrophosphatase
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DOI：
10.1126/science.1222505
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发表时间：
2012-07-27
期刊：
影响因子：
56.9
通讯作者：
Goldman, Adrian
中科院分区：
文献类型：
--
作者：
Kellosalo, Juho;Kajander, Tommi;Goldman, Adrian
膜整合焦磷酸酶 (M-PPase) 对于植物、细菌和原生动物寄生虫的生存至关重要。它们将焦磷酸盐水解或合成与 Na+ 或 H+ 泵送结合起来。静止状态下的海栖热袍菌 M-PPase 的 2.6 埃结构揭示了一种以前未知的离子泵解决方案。位于膜上方 20 埃的水解中心通过六个 a 螺旋的不寻常“耦合漏斗”与保守的 Asp(243)、Glu(246) 和 Lys(707) 形成的门耦合。与我们的产物复合物的 4.0 埃分辨率结构进行比较表明，螺旋 12 在底物结合时向下滑动，通过简单的结合变化机制打开大门。在闸门下方，四个螺旋形成出口通道。螺旋 3 至 6、9 至 12 和 13 至 16 的叠加表明 M-PPase 是通过基因三倍体产生的。
Membrane-integral pyrophosphatases (M-PPases) are crucial for the survival of plants, bacteria, and protozoan parasites. They couple pyrophosphate hydrolysis or synthesis to Na+ or H+ pumping. The 2.6-angstrom structure of Thermotoga maritima M-PPase in the resting state reveals a previously unknown solution for ion pumping. The hydrolytic center, 20 angstroms above the membrane, is coupled to the gate formed by the conserved Asp(243), Glu(246), and Lys(707) by an unusual "coupling funnel" of six a helices. Comparison with our 4.0-angstrom resolution structure of the product complex suggests that helix 12 slides down upon substrate binding to open the gate by a simple binding-change mechanism. Below the gate, four helices form the exit channel. Superimposing helices 3 to 6, 9 to 12, and 13 to 16 suggests that M-PPases arose through gene triplication.