Conformational flexibility of protein is essential for enzyme catalysis. Yet, how protein's conformational rearrangements and dynamics contribute to catalysis remains highly controversial. To unravel protein's role in catalysis, it is inevitable to understand the static and dynamic mechanisms simultaneously. To this end, here the Pin1-catalyzed isomerization reaction is studied from the two perspectives. The static view indicates that the hydrogen bonds involving Pin1 rearrange in a tightly coupled manner with isomerization. In sharp contrast, the isomerization dynamics are found to be very rapid; protein's slow conformational rearrangements thus cannot occur simultaneously with isomerization, and the reaction proceeds in a nonequilibrium manner. The distinctive protein conformations necessary to stabilize the transition state are prepared a priori, i.e., as conformational excited states. The present result suggests that enzymatic reaction is not a simple thermal activation from equilibrium directly to the transition state, thus adding a novel perspective to Pauling's view.
All Science Journal Classification (ASJC) codes
- Materials Science(all)
- Physical and Theoretical Chemistry