Conformational fitting of a flexible oligomeric substrate does not explain the enzymatic PET degradation

Joo et al. 1 have recently reported a crystal structure of a polyethylene terephthalate (PET) hydrolyzing enzyme ( Is PETase) from Ideonella sakaiensis which has been described able to metabolize PET at 30 °C 2 . They proposed a PET degradation mechanism solely based on covalent computational docking of an oligomeric substrate—2-hydroxyethyl-(monohydroxyethyl terephthalate) 4 —(2-HE(MHET) 4 ) into the substrate binding cleft of Is PETase without considering the motions and conformations of the PET polymer chain. Here we present a solid-state nuclear magnetic resonance (NMR) analysis of amorphous PET at the degradation temperature used by Joo et al. 1 , indicating that the highly stiff polymer chain can hardly resemble the suggested docking conformation of 2-HE(MHET) 4 . In correlation with the PET degradation performance obtained at the same temperature, Is PETase is unlikely to follow the catalytic mechanism proposed by Joo et al. 1 , which requires simultaneous binding and interaction of all four MHET substrate moieties with the binding site of the enzyme.