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Assessment of the PETase conformational changes induced by poly(ethylene terephthalate) binding
Author(s) -
Costa Clauber Henrique Souza,
Santos Alberto M.,
Alves Cláudio Nahum,
Martí Sérgio,
Moliner Vicent,
Santana Kauê,
Lameira Jerônimo
Publication year - 2021
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.26155
Subject(s) - terephthalic acid , molecular dynamics , chemistry , hydrolysis , active site , thermal stability , ethylene , enzyme , polymer , catalysis , stereochemistry , polyester , computational chemistry , organic chemistry
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 ( Is PETase) 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 Is 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 interactions of PET in the active site of Is PETase remain unclear. Herein, molecular docking and molecular dynamics (MD) simulations were applied to analyze structural changes of Is PETase induced by PET binding. Results from the essential dynamics revealed that the β1‐β2 connecting loop is very flexible. This loop is located far from the active site of Is PETase and we suggest that it can be considered for mutagenesis to increase the thermal stability of Is PETase. The free energy landscape (FEL) demonstrates that the main change in the transition between the unbound to the bound state is associated with the 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 Is 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 plastic polymers using biological systems.