PXD014299

PXD014299 is an original dataset announced via ProteomeXchange.

Title	A cleavable chelation-assisted biotin probe enables the discovery of a celecoxib binding site on prostaglandin E synthase
Description	The coxibs are a subset of non-steroidal anti-inflammatory drugs (NSAIDs) that selectively target cyclooxygenase-2 (COX-2) to inhibit prostaglandin signaling and reduce inflammation. However, only celecoxib remains in use, necessitating exploration of broader mechanisms of the coxibs. Here, we report a novel binding site for celecoxib on prostaglandin E synthase (PTGES), an enzyme downstream of COX-2 in the prostaglandin signaling pathway using an isotopically-coded cleavable chelation-assisted biotin probe. Evaluation of the multi-functional probe revealed significantly improved tagging efficiencies attributable to promotion of CuAAC chemistry by the embedded picolyl functional group. Application of the probe within the small molecule interactome mapping by photo-affinity labeling (SIM-PAL) platform using photo-celecoxib as a reporter for celecoxib identified known targets (e.g., carbonic anhydrase 12) and the significant enrichment of PTGES, along with six additional membrane proteins and 15 subunits of the cytochrome complex. In addition, four binding sites to celecoxib were mapped by the probe, including a direct interaction with PTGES. The interaction between celecoxib and PTGES was validated by competitive displacement and thermal shift assay. The binding site between celecoxib and PTGES enabled the development of a structural model of the interaction and will inform the further development of new selective inhibitors of the prostaglandin signaling pathway.
HostingRepository	PRIDE
AnnounceDate	2024-01-04
AnnouncementXML	Submission_2024-01-04_05:52:39.467.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Christina Woo
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue; deamidated residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2019-06-19 02:32:11	ID requested
⏵ 1	2024-01-04 05:52:40	announced

10.1021/acschembio.9b00511;

Miyamoto DK, Flaxman HA, Wu HY, Gao J, Woo CM, Discovery of a Celecoxib Binding Site on Prostaglandin E Synthase (PTGES) with a Cleavable Chelation-Assisted Biotin Probe. ACS Chem Biol, 14(12):2527-2532(2019) [pubmed]

submitter keyword: Human

Christina Woo
contact affiliation	Harvard University
contact email	cwoo@chemistry.harvard.edu
lab head
Christina Woo
contact affiliation	Harvard University
contact email	cwoo@chemistry.harvard.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD014299
     1. Label: PRIDE project
     2. Name: A cleavable chelation-assisted biotin probe enables the discovery of a celecoxib binding site on prostaglandin E synthase