The standard view of the origin of the catalytic properties of enzymes focuses on the binding energy differences between the ground state and the transition state arising from the arrangement of residues in the active site (i.e., statics). There is an alternative view that suggests that protein motions (i.e., dynamics) might play a role in catalysis. Klinman and co-workers recently published (Kohen, A.; Cannio, R.; Bartolucci, S.; Klinman, J. Nature 1999, 399, 496−499) findings on rate measurements in thermophilic alcohol dehydrogonase (ADH). At lower temperatures (below 30 °C), this enzyme undergoes a transition to a more rigid structure, and it was found that the corresponding apparent activation energy increases and the primary kinetic isotope effect (KIE) increases and becomes temperature-dependent. Explaining these results presents a challenge to theory. We show that a model of the reaction coordinate for the rate-determining step, coupled to an enzymatic environment and a specific strongly coupled active complex mode, can simultaneously explain a tunneling-dominated mechanism and the experimental trends reported by Klinman and co-workers. We propose a specific protein internal motion for the rate-promoting vibration and discuss other systems in which such motions might be dominant.