Prior work has proposed that these rotations of the conserved Trp are required to provide optimal aromatic interactions for stabilization of substrate binding. Our insights complement these observations, suggesting that easy access and switch between different conformers of the conserved Trp is required for productive binding of different substrate conformations and possibly for product release to enable continued hydrolysis. The latter requires PET hydrolysis experiments in the presence of degradation products and simulations of enzyme-product complexes addressing the molecular mechanisms of exiting the active site of PETases.