PXD051224

PXD051224 is an original dataset announced via ProteomeXchange.

Title	Copper(I)-Nitrene Platform for Chemoproteomics Profiling of Methionine
Description	Methionine plays a critical role in various biological and cell regulatory processes, making its chemoproteomic profiling indispensable for exploring its functions and potential in protein therapeutics. However, the advancement of methionine chemoproteomics is currently hindered by the scarcity of efficient labeling strategies. Methionine exhibits high kinetic reactivity and undergoes rapid oxidation due to the lower energy gap between Lowest Unoccupied Molecular Orbital (LUMO) and Highest Occupied Molecular Orbital (HOMO). Building on this unique high reactivity of methionine (Met), we introduce Copper(I)-Nitrene Platform (CuNiP) for robust, and selective labeling of Met to generate highly stable sulfonyl sulfimide conjugates under physiological conditions. We demonstrated the versatile proficiency of CuNiP to label methionine in a wide range of bioactive peptides, intact proteins (6.5-79.5 kDa) independent of molecular weight and 3D structures and proteins in complex cell lysate mixtures with varying payloads. Leveraging nitrene reactivity-based probes, we have discovered an array of new, previously undiscovered, ligandable proteins and sites harboring hyperreactive methionine within the landscape of the human proteome. Crucially, we employed CuNiP for live cell chemoproteomic profiling of methionine in breast (T47D) and prostate cancer (LnCap) cell lines, observing minimal cytotoxic effects and achieving dose-dependent labeling. Confocal imaging further revealed the spatial distribution of modified proteins within cell membrane, cytoplasm, and nucleus, underscoring the platform's potential in profiling the cellular interactome. This breakthrough, with its insights into live cell methionine labeling will deepen our understanding of protein biochemistry and also pioneers a transformative pathway in drug discovery.
HostingRepository	PRIDE
AnnounceDate	2024-04-24
AnnouncementXML	Submission_2024-04-24_06:11:13.363.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	David Gordon
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	carbamoylated residue; acetylated residue; deamidated residue
Instrument	Orbitrap Fusion Lumos; Bruker Daltonics timsTOF series

Revision	Datetime	Status	ChangeLog Entry
0	2024-04-05 11:22:14	ID requested
⏵ 1	2024-04-24 06:11:13	announced

Dataset with its publication pending

submitter keyword: Chemoproteomics, CuNiP, Methionine

David Ezra Gordon
contact affiliation	Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA, United States
contact email	david.ezra.gordon@emory.edu
lab head
David Gordon
contact affiliation	Emory University
contact email	david.ezra.gordon@emory.edu
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/2024/04/PXD051224

PRIDE project URI

• PRIDE
  1. PXD051224
     1. Label: PRIDE project
     2. Name: Copper(I)-Nitrene Platform for Chemoproteomics Profiling of Methionine