Enzyme Dynamics During Catalysis

TLDR

Enzyme dynamics are known to influence catalysis, yet motions directly linked to substrate turnover remain largely unknown. Atomic‑resolution NMR relaxation was used to monitor enzyme dynamics during catalysis. Conformational fluctuations of cyclophilin A’s active site on hundreds‑of‑microsecond timescales correlate with substrate turnover rates, enabling prediction of the reaction trajectory.

Abstract

Internal protein dynamics are intimately connected to enzymatic catalysis. However, enzyme motions linked to substrate turnover remain largely unknown. We have studied dynamics of an enzyme during catalysis at atomic resolution using nuclear magnetic resonance relaxation methods. During catalytic action of the enzyme cyclophilin A, we detect conformational fluctuations of the active site that occur on a time scale of hundreds of microseconds. The rates of conformational dynamics of the enzyme strongly correlate with the microscopic rates of substrate turnover. The present results, together with available structural data, allow a prediction of the reaction trajectory.