Journal Article

FZJ-2024-06051

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png From Bulk to Binding: Decoding the Entry of PET into Hydrolase Binding Pockets

Jäckering, A.FZJ* ; Göttsch, F. ; Schäffler, M.FZJ* ; Doerr, M. ; Bornscheuer, U. T. ; Wei, R. ; Strodel, B. (Corresponding author)FZJ*

2024
ACS Publications Washington, DC

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Please use a persistent id in citations: doi:10.1021/jacsau.4c00718  doi:10.34734/FZJ-2024-06051

Abstract: Plastic-degrading enzymes facilitate the biocatalyticrecycling of poly(ethylene terephthalate) (PET), a significantsynthetic polymer, and substantial progress has been made inutilizing PET hydrolases for industrial applications. To fully exploitthe potential of these enzymes, a deeper mechanistic understandingfollowed by targeted protein engineering is essential. Throughadvanced molecular dynamics simulations and free energy analysismethods, we elucidated the complete pathway from the initialbinding of two PET hydrolases�the thermophilic leaf-branchcompost cutinase (LCC) and polyester hydrolase 1 (PES-H1)�toan amorphous PET substrate, ultimately leading to a PET chainentering the active site in a hydrolyzable conformation. Ourfindings indicate that initial PET binding is nonspecific and drivenby polar and hydrophobic interactions. We demonstrate that the subsequent entry of PET into the active site can occur via one ofthree key pathways, identifying barriers related to both PET−PET and PET−enzyme interactions, as well as specific residueshighlighted through in silico and in vitro mutagenesis. These insights not only enhance our understanding of the mechanismsunderlying PET degradation and facilitate the development of targeted enzyme enhancement strategies but also provide a novelframework applicable to enzyme studies across various disciplines.

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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:
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