A chemical catalyst enabling histone acylation with endogenous acyl-CoA.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
22 09 2023
22 09 2023
Historique:
received:
27
07
2022
accepted:
29
08
2023
medline:
25
9
2023
pubmed:
22
9
2023
entrez:
22
9
2023
Statut:
epublish
Résumé
Life emerges from a network of biomolecules and chemical reactions catalyzed by enzymes. As enzyme abnormalities are often connected to various diseases, a chemical catalyst promoting physiologically important intracellular reactions in place of malfunctional endogenous enzymes would have great utility in understanding and treating diseases. However, research into such small-molecule chemical enzyme surrogates remains limited, due to difficulties in developing a reactive catalyst capable of activating inert cellular metabolites present at low concentrations. Herein, we report a small-molecule catalyst, mBnA, as a surrogate for a histone acetyltransferase. A hydroxamic acid moiety of suitable electronic characteristics at the catalytic site, paired with a thiol-thioester exchange process, enables mBnA to activate endogenous acyl-CoAs present in low concentrations and promote histone lysine acylations in living cells without the addition of exogenous acyl donors. An enzyme surrogate utilizing cellular metabolites will be a unique tool for elucidation of and synthetic intervention in the chemistry of life and disease.
Identifiants
pubmed: 37737243
doi: 10.1038/s41467-023-41426-z
pii: 10.1038/s41467-023-41426-z
pmc: PMC10517024
doi:
Substances chimiques
Histones
0
Acyl Coenzyme A
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
5790Informations de copyright
© 2023. Springer Nature Limited.
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