Department of Biochemistry and Synthetic Metabolism, Max Planck Institute for Terrestrial Microbiology, Marburg, Germany.
Microbial Protein Structure Group, Max Planck Institute for Terrestrial Microbiology, Marburg, Germany.
Nat Chem Biol. 2018 Dec;14(12):1127-1132. doi: 10.1038/s41589-018-0153-x. Epub 2018 Oct 29.
Cells must cope with toxic or reactive intermediates formed during metabolism. One coping strategy is to sequester reactions that produce such intermediates within specialized compartments or tunnels connecting different active sites. Here, we show that propionyl-CoA synthase (PCS), an ∼ 400-kDa homodimer, three-domain fusion protein and the key enzyme of the 3-hydroxypropionate bi-cycle for CO fixation, sequesters its reactive intermediate acrylyl-CoA. Structural analysis showed that PCS forms a multicatalytic reaction chamber. Kinetic analysis suggested that access to the reaction chamber and catalysis are synchronized by interdomain communication. The reaction chamber of PCS features three active sites and has a volume of only 33 nm. As one of the smallest multireaction chambers described in biology, PCS may inspire the engineering of a new class of dynamically regulated nanoreactors.
细胞必须应对代谢过程中形成的有毒或反应性中间产物。一种应对策略是将产生这些中间产物的反应隔离在专门的隔室或连接不同活性部位的隧道内。在这里，我们表明丙酰辅酶 A 合酶 (PCS) 是一种约 400kDa 的同源二聚体、三结构域融合蛋白，也是 CO2 固定的 3-羟基丙酸生物循环的关键酶，可将其反应性中间产物丙烯酰辅酶 A 隔离起来。结构分析表明，PCS 形成了一个多酶反应室。动力学分析表明，通过结构域间的通讯来同步进入反应室和催化反应。PCS 的反应室有三个活性位点，体积只有 33nm。作为生物学中描述的最小的多反应室之一，PCS 可能为动态调控纳米反应器的工程设计提供灵感。
