PXD027600

PXD027600 is an original dataset announced via ProteomeXchange.

Title	Activity-based protein profiling in human M2 macrophages using DHA-based photoaffinity probes
Description	17-Hydroxydocosahexaenoic acid (17-HDHA), an oxidative metabolite of the fish oil constituent docosahexaenoic acid (DHA, 22:6 n-3), is a signaling lipid with anti-inflammatory properties. The molecular mechanisms underlying the biological effect of 17-HDHA are poorly understood. Here, we report the design, synthesis and application of a complementary pair of bioorthogonal photoreactive probes based on the polyunsaturated scaffold of 17-HDHA and DHA. In these probes, an alkyne serves as a handle to introduce a fluorescent reporter group or a biotin-affinity tag via copper(I)-catalyzed azide-alkyne cycloaddition. This pair of chemical probes was used to map specific protein interaction partners of 17-HDHA in primary human macrophages, which led to the identification of prostaglandin reductase 1 (PTGR1) as a target of 17-HDHA, but not DHA. Ensuing biochemical studies revealed that PTGR1 converted 17-HDHA into 17-oxo-DHA, which inhibited the biosynthesis of the pro-inflammatory lipids 5-HETE and LTB4 in human macrophages and neutrophils.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_05:45:14.077.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Berend Gagestein
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Synapt MS

Revision	Datetime	Status	ChangeLog Entry
0	2021-07-27 07:39:30	ID requested
1	2023-04-28 02:38:31	announced
2	2023-11-14 08:45:23	announced	2023-11-14: Updated project metadata.
⏵ 3	2024-10-22 05:45:15	announced	2024-10-22: Updated project metadata.

10.1021/jacs.2c06827;

Gagestein B, von Hegedus JH, Kwekkeboom JC, Heijink M, Blomberg N, van der Wel T, Florea BI, van den Elst H, Wals K, Overkleeft HS, Giera M, Toes REM, Ioan-Facsinay A, van der Stelt M, Comparative Photoaffinity Profiling of Omega-3 Signaling Lipid Probes Reveals Prostaglandin Reductase 1 as a Metabolic Hub in Human Macrophages. J Am Chem Soc, 144(41):18938-18947(2022) [pubmed]

submitter keyword: Human, ABPP, photoaffinity, macrophage

Mario van der Stelt
contact affiliation	Molecular Physiology, Leiden Institute of Chemistry, Leiden University, The Netherlands
contact email	m.van.der.stelt@chem.leidenuniv.nl
lab head
Berend Gagestein
contact affiliation	Leiden University
contact email	b.gagestein@lic.leidenuniv.nl
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2023/04/PXD027600

PRIDE project URI

• PRIDE
  1. PXD027600
     1. Label: PRIDE project
     2. Name: Activity-based protein profiling in human M2 macrophages using DHA-based photoaffinity probes