A new conceptual framework for enzyme catalysis

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Abstract
Recent years have witnessed high levels of activity in identifying enzyme systems that catalyse H‐transfer by quantum tunneling. Rather than being restricted to a small number of specific enzymes as perceived initially, it has now become an accepted mechanism for H‐transfer in a growing number of enzymes. Furthermore, H‐tunneling is driven by the thermally induced dynamics of the enzyme. In some of those enzymes that break stable C–H bonds the reaction proceeds purely by quantum tunneling, without the need to partially ascend the barrier. Enzymes studied that fall into this category include the flavoprotein and quinoprotein amine dehydrogenases, which have proved to be excellent model systems. These enzymes have enabled us to study the relationship between barrier shape and reaction kinetics. This has involved studies with ‘slow’ and ‘fast’ substrates and enzymes impaired by mutagenesis. A number of key questions now remain, including the nature of the coupling between protein dynamics and quantum tunneling. The wide‐ranging implications of quantum tunneling introduce a paradigm shift in the conceptual framework for enzyme catalysis, inhibition and design.