Recently, a bacterium strain of Ideonella sakaiensis was identified with
the uncommon ability to degrade the poly(ethylene terephthalate) (PET).
The PETase from I. sakaiensis strain 201-F6 catalyzes the hydrolysis of
PET converting it to mono(2-hydroxyethyl) terephthalic acid (MHET),
bis(2-hydroxyethyl)-TPA (BHET), and terephthalic acid (TPA). Despite the
potential of this enzyme for mitigation or elimination of environmental
contaminants, one of the limitations of the use of PETase for PET
degradation is the fact that it acts only at moderate temperature due to
its low thermal stability. Besides, molecular details of the main
interaction of PET in the active site of PETase remains unclear. Herein,
molecular docking and molecular dynamics (MD) simulations were applied
to analyze structural changes of PETase induced by PET binding. Results
from the essential dynamics revealed that β1-β2 connecting loop is very
flexible. This Loop is located far from the active site of PETase and we
suggest that it can be considered for mutagenesis in order to increase
the thermal stability of PETase. The free energy landscape (FEL)
demonstrates that the main change in the transition between the
unbounded to the bounded state is associated with β7-α5 connecting loop,
where the catalytic residue Asp206 is located. Overall, the present
study provides insights into the molecular binding mechanism of PET into
the PETase structure and a computational strategy for mapping flexible
regions of this enzyme, which can be useful for the engineering of more
efficient enzymes for recycling the plastic polymers using biological
systems.
Assessment of the PETase Conformational Changes Induced by Poly(ethylene terephthalate) Binding
