厦门大学王斌举团队报道了预组织电场如何在催化循环中起作用以及酪氨酸羟化酶的例子。相关研究成果于2022年10月25日发表在国际顶尖学术期刊《美国化学会杂志》。

大自然设计了用于酶的静电催化本征电场（IEF）。但是，IEF如何在催化循环中涉及多个反应步骤的酶中靶向其功能？

为了破解IEF对酶系统催化循环的影响，研究人员对酪氨酸羟化酶（TyrH）进行了分子动力学和量子力学/分子力学（QM/MM）模拟。TyrH的催化循环包括两个反应阶段：第一阶段活化H₂O₂以形成化合物I的活性物种（Cpd I），第二阶段Cpd I介导的l-酪氨酸羟基化为l-DOPA。对于第一阶段，QM/MM计算表明丙酸血红素基团作为碱催化O-O异构化反应。

对于第二阶段，研究表明，反应由His88介导的质子耦合电子转移引发，随后氧原子从化合物II（Cpd II）转移至l-Tyr底物。重要的是，计算表明，TyrH中的IEF被优化以促进产生酶活性物种Cpd I的O-O键异构化。然而，相同的IEF减缓了随后的芳香族羟基化。因此，TyrH酶中的IEF不会催化产物形成步骤，但会选择性地促进催化循环中的一个或多个具有挑战性的步骤。研究发现对O₂/H₂O₂依赖性金属酶具有普遍意义，可以扩大人们对自然界如何利用电场作为“智能试剂”调节催化反应性的理解。

附：英文原文

Title: How Do Preorganized Electric Fields Function in Catalytic Cycles The Case of the Enzyme Tyrosine Hydroxylase

Author: Wei Peng, Shengheng Yan, Xuan Zhang, Langxing Liao, Jinyan Zhang, Sason Shaik, Binju Wang

Issue&Volume: October 25, 2022

Abstract: Nature has devised intrinsic electric fields (IEFs) that are engaged in electrostatic catalysis of enzymes. But, how does the IEF target its function in enzymes that involve several reaction steps in catalytic cycles To decipher the impact of the IEF on the catalytic cycle of an enzyme system, we have performed molecular dynamics and quantum-mechanical/molecular-mechanical (QM/MM) simulations on tyrosine hydroxylase (TyrH). The catalytic cycle of TyrH involves two reaction stages: the activation of H2O2 to form the active species of compound I (Cpd I), in the first stage, and the Cpd I-mediated hydroxylation of l-tyrosine to l-DOPA, in the second stage. For the first stage, the QM/MM calculations show that a heme-propionate group functions as a base to catalyze the O–O heterolysis reaction. For the second stage, the study reveals that the reaction is initiated by the His88-mediated proton-coupled electron transfer followed by the oxygen atom transfer from compound II (Cpd II) to the l-Tyr substrate. Importantly, our calculations demonstrate that the IEF in TyrH is optimized to promote the O–O bond heterolysis that generates the active species of the enzyme, Cpd I. However, the same IEF slows down the subsequent aromatic hydroxylation. Thus, the IEF in the TyrH enzymes does not catalyze the product formation step, but will selectively boost one or more challenging steps in the catalytic cycle. These findings have general implications on O2/H2O2-dependent metalloenzymes, which can expand our understanding of how nature has used electric fields as “smart reagents” in modulating the catalytic reactivity.

DOI: 10.1021/jacs.2c09263

Source: https://pubs.acs.org/doi/10.1021/jacs.2c09263