PXD035963

PXD035963 is an original dataset announced via ProteomeXchange.

Title	Chemoproteomic identification of a dipeptidyl peptidase 4 (DPP4) homolog in Bacteroides thetaiotaomicron important for envelope integrity and fitness
Description	Serine hydrolases play important roles in signaling and human metabolism, yet little is known about the functions of these enzymes 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 protease dipeptidyl peptidase 4 (hDPP4), a key enzyme that regulates insulin signaling. Functional studies reveal that BT4193 is a true homolog of hDPP4 while the other is misannotated and is a proline-specific triaminopeptidase. We demonstrate that BT4193 is important for envelope integrity and is inhibited by FDA-approved type 2 diabetes medications that target hDPP4. Loss of BT4193 reduces B. thetaiotaomicron fitness during in vitro growth within a diverse community. Taken together, our findings suggest that serine hydrolases contribute to gut microbiota dynamics and may be off-targets for existing drugs that could cause unintended impact on the microbiota.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_07:07:28.242.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Markus Lakemeyer
SpeciesList	scientific name: Bacteroides thetaiotaomicron (strain ATCC 29148 / DSM 2079 / NCTC 10582 / E50 / VPI-5482); NCBI TaxID: 226186;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2022-08-10 15:00:14	ID requested
1	2023-07-10 11:35:20	announced
⏵ 2	2023-11-14 07:07:28	announced	2023-11-14: Updated project metadata.

Dataset with its publication pending

submitter keyword: Activity-based protein profiling, protease,Microbiome

Matthew Bogyo
contact affiliation	Department of Pathology and Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305
contact email	mbogyo@stanford.edu
lab head
Markus Lakemeyer
contact affiliation	Institute for Organic and Macromolecular Chemistry Friedrich-Schiller-University Jena
contact email	markus.lakemeyer@uni-jena.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD035963
     1. Label: PRIDE project
     2. Name: Chemoproteomic identification of a dipeptidyl peptidase 4 (DPP4) homolog in Bacteroides thetaiotaomicron important for envelope integrity and fitness