Journal Article

FZJ-2024-05836

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Influence of Wobbling Tryptophan and Mutations on PET Degradation Explored by QM/MM Free Energy Calculations

Jäckering, A.FZJ* ; van der Kamp, M.Extern* ; Strodel, B. (Corresponding author)FZJ* ; Zinovjev, K.

2024
American Chemical Society Washington, DC

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Please use a persistent id in citations: doi:10.1021/acs.jcim.4c00776  doi:10.34734/FZJ-2024-05836

Abstract: ABSTRACT: Plastic-degrading enzymes, particularly poly(ethylene terephthalate)(PET) hydrolases, have garnered significant attention in recent years aspotential eco-friendly solutions for recycling plastic waste. However, understandingof their PET-degrading activity and influencing factors remainsincomplete, impeding the development of uniform approaches for enhancingPET hydrolases for industrial applications. A key aspect of PET hydrolaseengineering is optimizing the PET-hydrolysis reaction by lowering the associatedfree energy barrier. However, inconsistent findings have complicated these efforts.Therefore, our goal is to elucidate various aspects of enzymatic PET degradationby means of quantum mechanics/molecular mechanics (QM/MM) reactionsimulations and analysis, focusing on the initial reaction step, acylation, in twothermophilic PET hydrolases, LCC and PES-H1, along with their highly active variants, LCCIG and PES-H1FY. Our findingshighlight the impact of semiempirical QM methods on proton transfer energies, affecting the distinction between a two-step reactioninvolving a metastable tetrahedral intermediate and a one-step reaction. Moreover, we uncovered a concerted conformational changeinvolving the orientation of the PET benzene ring, altering its interaction with the side-chain of the “wobbling” tryptophan from Tstackingto parallel π−π interactions, a phenomenon overlooked in prior research. Our study thus enhances the understanding of theacylation mechanism of PET hydrolases, in particular by characterizing it for the first time for the promising PES-H1FY using QM/MM simulations. It also provides insights into selecting a suitable QM method and a reaction coordinate, valuable for future studieson PET degradation processes.

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Contributing Institute(s):

1. Strukturbiochemie (IBI-7)

Research Program(s):

1. 5241 - Molecular Information Processing in Cellular Systems (POF4-524) (POF4-524)

Appears in the scientific report 2024

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Database coverage:
; ; ; Clarivate Analytics Master Journal List ; Current Contents - Physical, Chemical and Earth Sciences ; Essential Science Indicators ; IF >= 5 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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