TY  - JOUR
AU  - Jäckering, Anna
AU  - van der Kamp, Marc
AU  - Strodel, Birgit
AU  - Zinovjev, Kirill
TI  - Influence of Wobbling Tryptophan and Mutations on PET Degradation Explored by QM/MM Free Energy Calculations
JO  - Journal of chemical information and modeling
VL  - 11
SN  - 1549-9596
CY  - Washington, DC
PB  - American Chemical Society
M1  - FZJ-2024-05836
SP  - acs.jcim.4c00776
PY  - 2024
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - 39344272
UR  - <Go to ISI:>//WOS:001325651400001
DO  - DOI:10.1021/acs.jcim.4c00776
UR  - https://juser.fz-juelich.de/record/1031817
ER  -