PXD051414

PXD051414 is an original dataset announced via ProteomeXchange.

Title	Precision Chemistry and Activity-Based Proteomics for Posttranslational Control of Protein Function
Description	Lysine acylations are ubiquitous and structurally diverse posttranslational modifications that vastly expand the functional heterogeneity of the human proteome. Hence, the targeted acylation of lysine residues has emerged as a strategic approach to exert biomimetic control over protein function. However, existing strategies for targeted lysine acylation in cells often rely on genetic intervention, recruitment of endogenous acylation machinery, or nonspecific acylating agents, and lack methods to quantify the magnitude of specific acylations on a global level. In this study, we develop activity-based acylome profiling (ABAP), a chemoproteomic strategy that exploits elaborate N-(cyanomethyl)-N-(phenylsulfonyl)amides and lysine-centric probes for site-specific introduction and proteome-wide mapping of posttranslational lysine acylations in human cells. Harnessing this framework, we quantify various artificial acylations and rediscover numerous endogenous lysine acylations. We validate site-specific acetylation of target lysines and establish structure-activity relationship for N-(cyanomethyl)-N-(phenylsulfonyl)amides in proteins from diverse structural and functional classes. We identify paralog-selective chemical probes that acetylate conserved lysines within interferon-stimulated antiviral RNA-binding proteins, generating de novo proteoforms with obstructed RNA interactions. We further demonstrate that targeted acetylation of a key enzyme in retinoid metabolism engenders a proteoform with a conformational change in protein structure, leading to a gain-of-function phenotype and reduced drug potency. These findings underscore the versatility of our strategy in biomimetic control over protein function through targeted delivery and global profiling of endogenous and artificial lysine acylations, potentially advancing therapeutic modalities and our understanding of biological processes orchestrated by these posttranslational modifications.
HostingRepository	PRIDE
AnnounceDate	2025-05-06
AnnouncementXML	Submission_2025-05-06_15:28:41.973.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Mikail Abbasov
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	Orbitrap Eclipse

Revision	Datetime	Status	ChangeLog Entry
0	2024-04-12 17:32:16	ID requested
⏵ 1	2025-05-06 15:28:42	announced

Ryan EM, Norinskiy MA, Bracken AK, Lueders EE, Chen X, Fu Q, Anderson ET, Zhang S, Abbasov ME, -(phenylsulfonyl)amides for Targeted Lysine Acylation and Post-Translational Control of Protein Function in Cells. J Am Chem Soc, 146(40):27622-27643(2024) [pubmed]

10.1021/jacs.4c09073;

submitter keyword: retinoid metabolism.,Posttranslational modifications, lysine conjugation, protein-RNA interactions, chemoproteomics, activity-based protein profiling, N-(cyanomethyl)-N-(phenylsulfonyl)amides

Mikail E. Abbasov
contact affiliation	Department of Chemistry and Chemical Biology
contact email	mikail.abbasov@cornell.edu
lab head
Mikail Abbasov
contact affiliation	Cornell University
contact email	abbasovgroupcornell@gmail.com
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/2025/05/PXD051414

PRIDE project URI

• PRIDE
  1. PXD051414
     1. Label: PRIDE project
     2. Name: Precision Chemistry and Activity-Based Proteomics for Posttranslational Control of Protein Function