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.

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Education, as an investment in human capital, is regarded as an important determinant of sustainable economic growth [1,2]. The purpose of this study is to explore the cointegration and causality between the investment in education and sustainable economic growth in Guangdong province by using the panel data of 21 cities from 2000 to 2016. We construct a variable intercept panel data model with an individual fixed effect based on the Cobb-Douglas production function, estimating the contribution of the investment in education to economic growth by introducing lags. The findings show the existence of the feedback causality between education and sustainable economic growth. Also, the results reveal that the local financial investment in education plays a positive and statistically significant role in promoting sustainable economic growth. However, the contribution of the local financial investment in education to economic growth varies in different areas. The investment in education in the Pearl River Delta region have the most obvious pull effects on its regional economy, whereas the Western region takes the second place. Meanwhile, the local financial investment in education for its role in promoting economic growth obviously has a two-year hysteresis effect. These findings have important implications for Guangdong’s solution to the imbalance between regional educational investment and sustainable economic growth.