增强的活性位点电场加速了酶催化。
Enhanced active-site electric field accelerates enzyme catalysis.
机构信息
Department of Chemistry, Stanford University, Stanford, CA, USA.
Stanford Synchrotron Radiation Lightsource, Menlo Park, CA, USA.
出版信息
Nat Chem. 2023 Dec;15(12):1715-1721. doi: 10.1038/s41557-023-01287-x. Epub 2023 Aug 10.
Abstract
The design and improvement of enzymes based on physical principles remain challenging. Here we demonstrate that the principle of electrostatic catalysis can be leveraged to substantially improve a natural enzyme's activity. We enhanced the active-site electric field in horse liver alcohol dehydrogenase by replacing the serine hydrogen-bond donor with threonine and replacing the catalytic Zn with Co. Based on the electric field enhancement, we make a quantitative prediction of rate acceleration-50-fold faster than the wild-type enzyme-which was in close agreement with experimental measurements. The effects of the hydrogen bonding and metal coordination, two distinct chemical forces, are described by a unified physical quantity-electric field, which is quantitative, and shown here to be additive and predictive. These results suggest a new design paradigm for both biological and non-biological catalysts.
摘要
基于物理原理的酶的设计和改进仍然具有挑战性。在这里，我们证明了静电催化原理可以被用来显著提高天然酶的活性。我们通过用苏氨酸取代丝氨酸的氢键供体，并将催化锌替换为钴，增强了马肝醇脱氢酶的活性部位电场。基于电场增强，我们对速率加速做出了定量预测——比野生型酶快 50 倍——这与实验测量结果非常吻合。氢键和金属配位这两种不同的化学力的影响可以用一个统一的物理量——电场来描述，这个物理量是定量的，并被证明是可加的和可预测的。这些结果为生物和非生物催化剂的设计提供了一个新的范例。
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