Photoaffinity Capture Compounds to Profile the Magic Spot Nucleotide Interactomes.
Alarmones
Magic Spot Nucleotides
Photoaffinity Proteomics
Stringent Response
ppGpp
Journal
Angewandte Chemie (International ed. in English)
ISSN: 1521-3773
Titre abrégé: Angew Chem Int Ed Engl
Pays: Germany
ID NLM: 0370543
Informations de publication
Date de publication:
23 05 2022
23 05 2022
Historique:
received:
31
01
2022
pubmed:
17
3
2022
medline:
18
5
2022
entrez:
16
3
2022
Statut:
ppublish
Résumé
Magic Spot Nucleotides (MSN) regulate the stringent response, a highly conserved bacterial stress adaptation mechanism, enabling survival under adverse external challenges. In times of antibiotic crisis, a detailed understanding of stringent response is essential, as potentially new targets for pharmacological intervention could be identified. In this study, we delineate the MSN interactome in Escherichia coli and Salmonella typhimurium applying a family of trifunctional photoaffinity capture compounds. We introduce MSN probes covering a diverse phosphorylation pattern, such as pppGpp, ppGpp, and pGpp. Our chemical proteomics approach provides datasets of putative MSN receptors both from cytosolic and membrane fractions that unveil new MSN targets. We find that the activity of the non-Nudix hydrolase ApaH is potently inhibited by pppGpp, which itself is converted to pGpp by ApaH. The capture compounds described herein will be useful to identify MSN interactomes across bacterial species.
Identifiants
pubmed: 35294098
doi: 10.1002/anie.202201731
pmc: PMC9310846
doi:
Substances chimiques
Bacterial Proteins
0
Nucleotides
0
Guanosine Tetraphosphate
33503-72-9
Guanosine Pentaphosphate
38918-96-6
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e202201731Informations de copyright
© 2022 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.
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