Connecting Conformational Motions to Rapid Dynamics in Human Purine Nucleoside Phosphorylase.
Connecting Conformational Motions to Rapid Dynamics in Human Purine Nucleoside Phosphorylase.
复制标题
将构象运动与人嘌呤核苷磷酸化酶的快速动力学联系起来。
DOI：
10.1021/acs.jpcb.2c07243
复制
发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Schwartz,StevenD
中科院分区：
文献类型：
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作者：
Frost,ClaraF;Balasubramani,SreeGanesh;Antoniou,Dimitri;Schwartz,StevenD
蛋白质运动对酶催化的影响仍然是一个积极讨论的话题。蛋白质运动发生在不同的时间尺度上，从飞秒的振动波动到毫秒的集体运动。有许多研究表明，构象运动可能有助于催化、蛋白质折叠和底物特异性。通过过渡路径采样研究也知道，快速促进振动有助于酶催化。人嘌呤核苷磷酸化酶（PNP）是一种既具有重要的构象运动又具有快速促进振动的酶。这种酶的缓慢运动与环运动有关，当打开时允许底物进入和产物释放，但在催化过程中关闭活性位点。我们研究了无约束的PNP结构和环运动有约束的PNP结构之间的区别。为了研究慢速和快速蛋白质动力学之间可能的耦合，我们采用了过渡路径采样、反应坐标识别、电场计算和自由能计算。
The influence of protein motions on enzyme catalysis remains a topic of active discussion. Protein motions occur across a variety of time scales, from vibrational fluctuations in femtoseconds, to collective motions in milliseconds. There have been numerous studies that show conformational motions may assist in catalysis, protein folding, and substrate specificity. It is also known through transition path sampling studies that rapid promoting vibrations contribute to enzyme catalysis. Human purine nucleoside phosphorylase (PNP) is one enzyme that contains both an important conformational motion and a rapid promoting vibration. The slower motion in this enzyme is associated with a loop motion, that when open allows substrate entry and product release but closes over the active site during catalysis. We examine the differences between an unconstrained PNP structure and a PNP structure with constraints on the loop motion. To investigate possible coupling between the slow and fast protein dynamics, we employed transition path sampling, reaction coordinate identification, electric field calculations, and free energy calculations reported here.