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Exploring the Reaction Mechanism of Polyethylene Terephthalate Biodegradation through QM/MM Approach.

ABSTRACT: The enzyme PETase fromIdeonella sakaiensis (IsPETase) strain 201-F6 can catalyze the hydrolysis of polyethylene terephthalate (PET), mainly converting it into mono(2-hydroxyethyl) terephthalic acid (MHET). In this study, we used quantum mechanics/molecular mechanics (QM/MM) simulations to explore the molecular details of the catalytic reaction mechanism of IsPETase in the formation of MHET. The QM region was described with AM1d/PhoT and M06-2X/6-31+G(d,p) potential. QM/MM simulations unveil the complete enzymatic PET hydrolysis mechanism and identify two possible reaction pathways for acylation and deacylation steps. The barrier obtained at M06-2X/6-31+G(d,p)/MM potential for the deacylation step corresponds to 20.4 kcal/mol, aligning with the experimental value of 18 kcal/mol. Our findings indicate that deacylation is the rate-limiting step of the process. Furthermore, per-residue interaction energy contributions revealed unfavorable contributions to the transition state of amino acids located at positions 200-230, suggesting potential sites for targeted mutations. These results can contribute to the development of more active and selective enzymes for PET depolymerization.

SUBMITTER: Dos Santos AM

PROVIDER: S-EPMC11317977 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature

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Exploring the Reaction Mechanism of Polyethylene Terephthalate Biodegradation through QM/MM Approach.

Dos Santos Alberto M AM da Costa Clauber H S CHS Silva Pedro H A PHA Skaf Munir S MS Lameira Jerônimo J

The journal of physical chemistry. B 20240729 31

The enzyme PETase fromIdeonella sakaiensis (IsPETase) strain 201-F6 can catalyze the hydrolysis of polyethylene terephthalate (PET), mainly converting it into mono(2-hydroxyethyl) terephthalic acid (MHET). In this study, we used quantum mechanics/molecular mechanics (QM/MM) simulations to explore the molecular details of the catalytic reaction mechanism of IsPETase in the formation of MHET. The QM region was described with AM1d/PhoT and M06-2X/6-31+G(d,p) potential. Q ...[more]

PMID: 39072475

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Project description:Human arginase I (HARGI) is a metalloprotein highly expressed in the liver cytosol and catalyzes the hydrolysis of l-arginine to form l-ornithine and urea. Understanding the reaction mechanism would be highly helpful to design new inhibitor molecules for HARGI as it is a target for heart- and blood-related diseases. In this study, we explored the hydrolysis reaction mechanism of HARGI with antiferromagnetic and ferromagnetic coupling between two Mn(II) ions at the catalytic site by employing molecular dynamics simulations coupled with quantum mechanics and molecular mechanics (QM/MM). The spin states, high-spin ferromagnetic couple (S Mn1 = 5/2, S Mn2 = 5/2), low-spin ferromagnetic couple (S Mn1 = 1/2, S Mn2 = 1/2), high-spin antiferromagnetic couple (S Mn1 = 5/2, S Mn2 = -5/2), and low-spin antiferromagnetic couple (S Mn1 = 1/2, S Mn2 = -1/2) are considered, and the calculated energetics for the complex of the substrate and HARGI are compared. The results show that the high-spin antiferromagnetic couple (S Mn1 = 5/2, S Mn2 = -5/2) is more stable than other spin states. The low-spin ferromagnetic and antiferromagnetic coupled states are highly unstable compared with the corresponding high-spin states. The high-spin antiferromagnetic couple (S Mn1 = 5/2, S Mn2 = -5/2) is stabilized by 0.39 kcal/mol compared with the ferromagnetic couple (S Mn1 = 5/2, S Mn2 = 5/2). The reaction mechanism is independent of spin states; however, the energetics of transition states and intermediates are more stable in the case of the high-spin antiferromagnetic couple (S Mn1 = 5/2, S Mn2 = -5/2) than the corresponding ferromagnetic state. It is evident that the calculated coupling constants are higher for antiferromagnetic states and, interestingly, superexchange coupling is found to occur between Mn(II) ions via hydroxide ions in a reactant. The hydroxide ion enhances the coupling interaction and initiates the catalytic reaction. It is also noted that the first intermediate structure where there is no superexchange coupling is similar to the known inhibitor 2(S)-amino-6-boronohexanoic acid.

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Exploring the Reaction Mechanism of Polyethylene Terephthalate Biodegradation through QM/MM Approach.

Publications

Exploring the Reaction Mechanism of Polyethylene Terephthalate Biodegradation through QM/MM Approach.

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