PXD028270

PXD028270 is an original dataset announced via ProteomeXchange.

Title	A Paal-Knorr agent for chemoproteomic profiling of targets of isoketals in cells
Description	Natural systems produce various γ-dicarbonyl-bearing compounds that can covalently modify lysine in protein targets via the classic Paal-Knorr reaction. Among them is a unique class of lipid-derived electrophiles - isoketals that exhibit high chemical reactivity and critical biological functions. However, it remains unknown about their target selectivity and profiles in complex proteomes. Here we report a Paal-Knorr agent, 4-oxonon-8-ynal (herein termed ONAyne), for a proteome-wide selectivity survey and quantitative reactivity profiling of the γ-dicarbonyl warhead. Furthermore, combined with quantitative chemoproteomics in a competitive format, ONAyne permitted global, in situ, and site-specific profiling of targeted lysine residues of two specific isomers of isoketals, levuglandin (LG) D2 and E2. The functional analyses reveal that LGs-derived adduction drives inhibition of malate dehydrogenase MDH2 and exhibits a crosstalk with two epigenetic marks on histone H2B in macrophages. Our approach should be broadly useful for target profiling of bioactive γ-dicarbonyls in diverse biological contexts.
HostingRepository	PRIDE
AnnounceDate	2022-02-15
AnnouncementXML	Submission_2022-02-15_13:11:09.578.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Wang Min-ran
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF-X

Revision	Datetime	Status	ChangeLog Entry
0	2021-09-09 08:00:20	ID requested
⏵ 1	2022-02-15 13:11:10	announced

Wang MR, He JY, He JX, Liu KK, Yang J, A Paal-Knorr agent for chemoproteomic profiling of targets of isoketals in cells. Chem Sci, 12(43):14557-14563(2021) [pubmed]

submitter keyword: Paal-Knorr reaction, isoketals, ONAyne, chemoproteomics

Jing Yang
contact affiliation	State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences • Beijing, Beijing Institute of Lifeomics, Beijing, China
contact email	yangjing@ncpsb.org.cn
lab head
Wang Min-ran
contact affiliation	National Center for Protein Sciences • Beijing
contact email	13833683803@163.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD028270
     1. Label: PRIDE project
     2. Name: A Paal-Knorr agent for chemoproteomic profiling of targets of isoketals in cells