Chemoproteomic identification of a DPP4 homolog in Bacteroides thetaiotaomicron.
Nat Chem Biol
; 19(12): 1469-1479, 2023 Dec.
Article
en En
| MEDLINE
| ID: mdl-37349583
ABSTRACT
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.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Diabetes Mellitus Tipo 2
/
Bacteroides thetaiotaomicron
Tipo de estudio:
Diagnostic_studies
Límite:
Humans
Idioma:
En
Revista:
Nat Chem Biol
Asunto de la revista:
BIOLOGIA
/
QUIMICA
Año:
2023
Tipo del documento:
Article
País de afiliación:
Estados Unidos