PXD039334

PXD039334 is an original dataset announced via ProteomeXchange.

Title	Identification of global inhibitors of cellular glycosylation
Description	Small molecule inhibitors of glycosylation enzymes are valuable tools for dissecting glycan functions and potential drug candidates. Screening for inhibitors of glycosyltransferases are mainly performed by in vitro enzyme assays with difficulties moving candidates to cells and animals. Here, we circumvent this by employing a cell-based screening assay using glycoengineered cells expressing tailored reporter glycoproteins. We focused on GalNAc-type O-glycosylation, and selected the GalNAc-T11 isoenzyme that selectively glycosylates the endocytic low density lipoprotein receptor (LDLR)-related proteins as target. Our screen of a limited small molecule compound library did not identify selective inhibitors of GalNAc-T11, however we identified two compounds that broadly inhibited Golgi-localized glycosylation processes. These compounds mediated reversible fragmentation of the Golgi system without affecting secretion. We demonstrate how these inhibitors can be used to manipulate glycosylation in cells to induce expression of truncated O-glycans and augment binding of cancer-specific Tn-glycoprotein antibodies and to inhibit expression of heparan sulfate and binding and infection of SARS-CoV-2.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:45:30.313.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Adnan Halim
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; hexosylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2023-01-09 02:32:38	ID requested
1	2023-05-05 05:38:27	announced
⏵ 2	2023-11-14 08:45:31	announced	2023-11-14: Updated project metadata.

S, ø, rensen DM, B, ü, ll C, Madsen TD, Lira-Navarrete E, Clausen TM, Clark AE, Garretson AF, Karlsson R, Pijnenborg JFA, Yin X, Miller RL, Chanda SK, Boltje TJ, Schjoldager KT, Vakhrushev SY, Halim A, Esko JD, Carlin AF, Hurtado-Guerrero R, Weigert R, Clausen H, Narimatsu Y, Identification of global inhibitors of cellular glycosylation. Nat Commun, 14(1):948(2023) [pubmed]

submitter keyword: Golgi fragmentation, cell-based glycan array, O-glycosylation, SARS-CoV-2, compound library screen,Glycosylation inhibitor, glycosyltransferases

Henrik Clausen
contact affiliation	Copenhagen Center for Glycomics (CCG), Department of Cellular and Molecular Medicine, University of Copenhagen, Denmark
contact email	hclau@sund.ku.dk
lab head
Adnan Halim
contact affiliation	University of Copenhagen
contact email	halim@sund.ku.dk
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/2023/05/PXD039334

PRIDE project URI

• PRIDE
  1. PXD039334
     1. Label: PRIDE project
     2. Name: Identification of global inhibitors of cellular glycosylation