The High-Affinity Chymotrypsin Inhibitor Eglin C Poorly Inhibits Human Chymotrypsin-Like Protease: Gln192 and Lys218 Are Key Determinants.
eglin C
human chymotrypsin‐like enzyme
molecular dynamics
protein–protein interaction
serine proteinase
serine proteinase inhibitor
Journal
Proteins
ISSN: 1097-0134
Titre abrégé: Proteins
Pays: United States
ID NLM: 8700181
Informations de publication
Date de publication:
20 Sep 2024
20 Sep 2024
Historique:
revised:
17
08
2024
received:
28
05
2024
accepted:
06
09
2024
medline:
20
9
2024
pubmed:
20
9
2024
entrez:
20
9
2024
Statut:
aheadofprint
Résumé
Eglin C, a small protein from the medicinal leech, has been long considered a general high-affinity inhibitor of chymotrypsins and elastases. Here, we demonstrate that eglin C inhibits human chymotrypsin-like protease (CTRL) weaker by several orders of magnitude than other chymotrypsins. In order to identify the underlying structural aspects of this unique deviation, we performed comparative molecular dynamics simulations on experimental and AlphaFold model structures of bovine CTRA and human CTRL. Our results indicate that in CTRL, the primary determinants of the observed weak inhibition are amino-acid positions 192 and 218 (using conventional chymotrypsin numbering), which participate in shaping the S1 substrate-binding pocket and thereby affect the stability of the protease-inhibitor complexes.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Magyar Tudományos Akadémia
Organisme : NIH HHS
ID : R01 DK082412
Pays : United States
Organisme : NIH HHS
ID : R01 DK117809
Pays : United States
Organisme : National Research, Development and Innovation Fund of Hungary
ID : 2018-1.2.1-NKP-2018-00005
Organisme : National Research, Development and Innovation Fund of Hungary
ID : 2018-1.2.1-NKP
Organisme : National Research Development and Innovation Office (Hungarian Scientific Research Fund)
ID : K119386
Organisme : National Research Development and Innovation Office (Hungarian Scientific Research Fund)
ID : K135289
Organisme : European Regional Development Fund
Organisme : Ministry of Human Capacities in Hungary
Organisme : European Union
ID : VEKOP-2.3.2-16-2017-00014
Organisme : European Union
ID : RRF-2.3.1-21-2022-00015
Informations de copyright
© 2024 The Author(s). PROTEINS: Structure, Function, and Bioinformatics published by Wiley Periodicals LLC.
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