Chemoproteomic identification of a DPP4 homolog in Bacteroides thetaiotaomicron.
Journal
Nature chemical biology
ISSN: 1552-4469
Titre abrégé: Nat Chem Biol
Pays: United States
ID NLM: 101231976
Informations de publication
Date de publication:
Dec 2023
Dec 2023
Historique:
received:
01
08
2022
accepted:
08
05
2023
medline:
27
11
2023
pubmed:
23
6
2023
entrez:
22
6
2023
Statut:
ppublish
Résumé
Serine hydrolases have important roles in signaling and human metabolism, yet little is known about their functions in gut commensal bacteria. Using bioinformatics and chemoproteomics, we identify serine hydrolases in the gut commensal Bacteroides thetaiotaomicron that are specific to the Bacteroidetes phylum. Two are predicted homologs of the human dipeptidyl peptidase 4 (hDPP4), a key enzyme that regulates insulin signaling. Our functional studies reveal that BT4193 is a true homolog of hDPP4 that can be inhibited by FDA-approved type 2 diabetes medications targeting hDPP4, while the other is a misannotated proline-specific triaminopeptidase. We demonstrate that BT4193 is important for envelope integrity and that loss of BT4193 reduces B. thetaiotaomicron fitness during in vitro growth within a diverse community. However, neither function is dependent on BT4193 proteolytic activity, suggesting a scaffolding or signaling function for this bacterial protease.
Identifiants
pubmed: 37349583
doi: 10.1038/s41589-023-01357-8
pii: 10.1038/s41589-023-01357-8
doi:
Substances chimiques
Dipeptidyl Peptidase 4
EC 3.4.14.5
Serine
452VLY9402
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1469-1479Informations de copyright
© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.
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