A 21st century revisionist's view at a turning point in enzymology

Despite the fact that the number of publications associated with the keyword 'enzyme' increases every year, the precise origin of enzyme catalysis has remained unresolved. Because of sustained intensive research efforts from an increasing number of laboratories, detailed information regarding the physics, chemistry and kinetics of enzymes is accumulating rapidly. The growing body of data contains many examples of kinetic behavior that are incompatible with a static view of enzyme catalysis. As a result, numerous laboratories are approaching the consensus that protein motion plays an essential role in enzyme catalysis. A model that incorporates nuclear quantum tunneling together with two classes of protein motion termed conformational sampling (pre-organization) and reorganization-is recommended as a means of understanding the large body of data for enzyme-catalyzed hydrogen transfers. It should also serve as a vehicle for future efforts in the development of potent enzyme inhibitors and the de novo design of all classifications of enzymes.