Structure, catalysis, chitin transport, and selective inhibition of chitin synthase.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
08 08 2023
08 08 2023
Historique:
received:
11
08
2022
accepted:
28
07
2023
medline:
10
8
2023
pubmed:
9
8
2023
entrez:
8
8
2023
Statut:
epublish
Résumé
Chitin is one of the most abundant natural biopolymers and serves as a critical structural component of extracellular matrices, including fungal cell walls and insect exoskeletons. As a linear polymer of β-(1,4)-linked N-acetylglucosamine, chitin is synthesized by chitin synthases, which are recognized as targets for antifungal and anti-insect drugs. In this study, we determine seven different cryo-electron microscopy structures of a Saccharomyces cerevisiae chitin synthase in the absence and presence of glycosyl donor, acceptor, product, or peptidyl nucleoside inhibitors. Combined with functional analyses, these structures show how the donor and acceptor substrates bind in the active site, how substrate hydrolysis drives self-priming, how a chitin-conducting transmembrane channel opens, and how peptidyl nucleoside inhibitors inhibit chitin synthase. Our work provides a structural basis for understanding the function and inhibition of chitin synthase.
Identifiants
pubmed: 37553334
doi: 10.1038/s41467-023-40479-4
pii: 10.1038/s41467-023-40479-4
pmc: PMC10409773
doi:
Substances chimiques
Chitin Synthase
EC 2.4.1.16
Chitin
1398-61-4
Nucleosides
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4776Informations de copyright
© 2023. Springer Nature Limited.
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