%0 Journal Article
%A Jäckering, Anna
%A van der Kamp, Marc
%A Strodel, Birgit
%A Zinovjev, Kirill
%T Influence of Wobbling Tryptophan and Mutations on PET Degradation Explored by QM/MM Free Energy Calculations
%J Journal of chemical information and modeling
%V 11
%@ 1549-9596
%C Washington, DC
%I American Chemical Society
%M FZJ-2024-05836
%P acs.jcim.4c00776
%D 2024
%X 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.
%F PUB:(DE-HGF)16
%9 Journal Article
%$ 39344272
%U <Go to ISI:>//WOS:001325651400001
%R 10.1021/acs.jcim.4c00776
%U https://juser.fz-juelich.de/record/1031817