Overcoming the Bottleneck of the Enzymatic Cycle by Steric Frustration
Overcoming the Bottleneck of the Enzymatic Cycle by Steric Frustration
复制标题
通过空间受阻克服酶促循环的瓶颈
DOI：
10.1103/physrevlett.122.238102
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发表时间：
2019-06-14
影响因子：
8.6
通讯作者：
Wang, Wei
中科院分区：
文献类型：
--
作者：
Li, Wenfei;Wang, Jun;Wang, Wei
天然酶的巨大催化能力依赖于克服酶循环中瓶颈事件的能力，但其潜在的物理机制尚未完全了解。在这里，通过进行分子模拟的整个酶循环的模型多底物酶与动态能量景观模型，我们表明，多底物酶可以利用空间位阻，以促进限速产品释放步骤。在酶循环过程中，瓶颈产物通过底物-产物共结合复合物的群体在相邻位点处通过新底物的结合而被主动挤出，其中结合口袋由于空间不相容性而受到阻碍。因此，这种空间阻挫能够实现由底物结合能驱动的产物释放的主动机制，从而促进酶循环。
The enormous catalytic power of natural enzymes relies on the ability to overcome the bottleneck event in the enzymatic cycle, yet the underlying physical mechanisms are not fully understood. Here, by performing molecular simulations of the whole enzymatic cycle for a model multisubstrate enzyme with a dynamic energy landscape model, we show that multisubstrate enzymes can utilize steric frustration to facilitate the rate-limiting product-release step. During the enzymatic cycles, the bottleneck product is actively squeezed out by the binding of a new substrate at the neighboring site through the population of a substrate-product cobound complex, in which the binding pockets are frustrated due to steric incompatibility. Such steric frustration thereby enables an active mechanism of product release driven by substrate-binding energy, facilitating the enzymatic cycle.