Furthermore, pulling simulations where we pull products PRFAR and CdRP out of the SeHisA(dup13-15/D10G/G102A/Q24L) active site (the only variant from the real-time evolution experiment with a PRFAR-bound crystallographic structure) show significant conformational changes in both loops 1 and 6 when pulling PRFAR out of the active site, whereas when pulling CdRP out of the active site, loop 1 is much more stable and the main requirement is for loop 6 to open. This suggests that loop 1 dynamics are more important for binding of ProFAR and subsequent release of PRFAR, than for the smaller substrate PRA and its product CdRP, whereas loop 1 dynamics appears to be critical to catalysis (Table ). In addition, the substantial rearrangements that we observe for both compounds suggests that a slow (potentially rate-limiting) product release step is the reason for the low turnover numbers observed for an otherwise facile reaction, further providing evidence that turnover rates are being regulated by loop dynamics.