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PXD051414

PXD051414 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitlePrecision Chemistry and Activity-Based Proteomics for Posttranslational Control of Protein Function
DescriptionLysine 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.
HostingRepositoryPRIDE
AnnounceDate2025-05-06
AnnouncementXMLSubmission_2025-05-06_15:28:41.973.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterMikail Abbasov
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListiodoacetamide derivatized residue
InstrumentOrbitrap Eclipse
Dataset History
RevisionDatetimeStatusChangeLog Entry
02024-04-12 17:32:16ID requested
12025-05-06 15:28:42announced
Publication List
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;
Keyword List
submitter keyword: retinoid metabolism.,Posttranslational modifications, lysine conjugation, protein-RNA interactions, chemoproteomics, activity-based protein profiling, N-(cyanomethyl)-N-(phenylsulfonyl)amides
Contact List
Mikail E. Abbasov
contact affiliationDepartment of Chemistry and Chemical Biology
contact emailmikail.abbasov@cornell.edu
lab head
Mikail Abbasov
contact affiliationCornell University
contact emailabbasovgroupcornell@gmail.com
dataset submitter
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