High pressure & low temperature study of the mechanism of enzymatic hydrogen tunnelling: promoting motions vs multiple kinetically distinct substates

点击翻译按钮获取中文摘要

All reactions in living systems are mediated and speeded by protein catalysts. The rate accelerations achieved by Nature's catalysts are often as high as 20 orders of magnitude. An understanding of the mechanisms by which enzymes accelerate chemical reactions is of central importance for a wide range of disciplines and industries. In general terms the rate of every reaction is increased when the activation energy for this reaction, which separates the reactants from the products, is reduced. It has recently become clear that particles like electrons, protons, hydrogen atoms, and hydride ions can also tunnel through this activation barrier thereby avoiding the need to climb the activation barrier. The mechanism by which these tunnelling reactions occur has been the subject of much debate. Several groups have used a theoretical model to explain the experimentally observed dependence of the reactions rates on temperature. This model proposes that the dynamic motions of the enzyme couple to the actual reaction and thereby promote it. Such a model could explain many experimental results. However, there are still many controversies and it is important to test this model. In addition, we and others have proposed alternative explanations which are based on the observations that many enzymes do not have only one rigid and well defined conformation, but are made up of an ensemble of similar but structurally distinct substates which have different catalytic properties. This is a conceptionally different and more classical view of enzymes which should allow the explanation of many observations. The work proposed here will not only shed light on a fundamental problem of physical sciences, but should eventually lead to the design of artificial catalysts, which display activity in non-physiological environments, and of enzyme inhibitors with many benefits in health care and agriculture.