% IMPORTANT: The following is UTF-8 encoded. This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.
@ARTICLE{Jckering:1032182,
author = {Jäckering, Anna and Göttsch, Frederike and Schäffler,
Moritz and Doerr, Mark and Bornscheuer, Uwe T. and Wei, Ren
and Strodel, Birgit},
title = {{F}rom {B}ulk to {B}inding: {D}ecoding the {E}ntry of {PET}
into {H}ydrolase {B}inding {P}ockets},
journal = {JACS Au},
volume = {4},
number = {10},
issn = {2691-3704},
address = {Washington, DC},
publisher = {ACS Publications},
reportid = {FZJ-2024-06051},
pages = {4000 - 4012},
year = {2024},
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.},
cin = {IBI-7},
ddc = {540},
cid = {I:(DE-Juel1)IBI-7-20200312},
pnm = {5241 - Molecular Information Processing in Cellular Systems
(POF4-524)},
pid = {G:(DE-HGF)POF4-5241},
typ = {PUB:(DE-HGF)16},
pubmed = {39483243},
UT = {WOS:001323931400001},
doi = {10.1021/jacsau.4c00718},
url = {https://juser.fz-juelich.de/record/1032182},
}