Piephoff D Evan, Wu Jianlan, Cao Jianshu
Department of Chemistry, Massachusetts Institute of Technology , Cambridge, Massachusetts 02139, United States.
J Phys Chem Lett. 2017 Aug 3;8(15):3619-3623. doi: 10.1021/acs.jpclett.7b01210. Epub 2017 Jul 24.
In a conformational nonequilibrium steady state (cNESS), enzyme turnover is modulated by the underlying conformational dynamics. On the basis of a discrete kinetic network model, we use an integrated probability flux balance method to derive the cNESS turnover rate for a conformation-modulated enzymatic reaction. The traditional Michaelis-Menten (MM) rate equation is extended to a generalized form, which includes non-MM corrections induced by conformational population currents within combined cyclic kinetic loops. When conformational detailed balance is satisfied, the turnover rate reduces to the MM functional form, explaining its general validity. For the first time, a one-to-one correspondence is established between non-MM terms and combined cyclic loops with unbalanced conformational currents. Cooperativity resulting from nonequilibrium conformational dynamics can be achieved in enzymatic reactions, and we provide a novel, rigorous means of predicting and characterizing such behavior. Our generalized MM equation affords a systematic approach for exploring cNESS enzyme kinetics.
在构象非平衡稳态（cNESS）中，酶的周转受潜在构象动力学的调节。基于离散动力学网络模型，我们使用综合概率通量平衡方法来推导构象调节酶促反应的cNESS周转速率。传统的米氏（MM）速率方程被扩展为广义形式，其中包括由组合循环动力学回路内的构象群体电流引起的非MM校正。当满足构象详细平衡时，周转速率简化为MM函数形式，解释了其普遍有效性。首次在非MM项与具有不平衡构象电流的组合循环回路之间建立了一一对应关系。酶促反应中可以实现由非平衡构象动力学产生的协同性，并且我们提供了一种预测和表征此类行为的新颖、严格的方法。我们的广义MM方程为探索cNESS酶动力学提供了一种系统方法。
