PXD019204

PXD019204 is an original dataset announced via ProteomeXchange.

Title	An azidoribose probe to track ketoamine adducts in histone ribose glycation (293T nuclei - LFQ)
Description	Reactive cellular metabolites can modify macromolecules and form adducts known as non-enzymatic covalent modifications (NECMs). Dissecting the mechanisms, regulation and consequences of NECMs, such as glycation, has been challenging due to the complex and often ambiguous nature of the adducts formed. Directly tracking the formation of modifications on key targets to uncover their underlying physiological importance requires specific chemical tools. Here we present the novel chemoenzymatic syntheses of an active azido-modified ribose analog, 5-azidoribose (5-AR), as well as an inactive control derivative, 1-azidoribose (1-AR) and their application towards understanding protein ribose-glycation in vitro and in cellulo. With these new probes we found that, similar to MGO-glycation, ribose glycation specifically accumulates on histones. In addition to fluorescent labeling, we demonstrate the utility of the probe in enriching modified targets, which were identified by label-free quantitative proteomics and highresolution MS/MS workflows. Finally, we establish that the known oncoprotein and hexose deglycase, fructosamine 3-kinase (FN3K), recognizes and facilitates the removal of 5-AR glycation adducts in live cells, supporting the dynamic regulation of ribose glycation as well as validating the probe as a new chemical tool to monitor FN3K activity. Altogether, we demonstrate this probe’s utilities to uncover ribose-glycation and deglycation events as well as tracking FN3K activity towards establishing its potential as a new cancer vulnerability.
HostingRepository	PRIDE
AnnounceDate	2020-05-15
AnnouncementXML	Submission_2020-05-15_03:02:10.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Igor Maksimovic
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2020-05-14 07:19:31	ID requested
⏵ 1	2020-05-15 03:02:11	announced

Maksimovic I, Zheng Q, Trujillo MN, Galligan JJ, David Y, An Azidoribose Probe to Track Ketoamine Adducts in Histone Ribose Glycation. J Am Chem Soc, 142(22):9999-10007(2020) [pubmed]

ProteomeXchange project tag: Biology/Disease-Driven Human Proteome Project (B/D-HPP), Human Proteome Project

submitter keyword: Histones, ribose, glycation, click chemistry, epigenetics, proteomics

Yael David
contact affiliation	Tri-Institutional Program, New York, NY, United States; Chemical Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, United States; Department of Pharmacology, Weill Cornell Medical College, New York, NY, United States; Department of Physiology, Biophysics and Systems Biology, Weill Cornell Medical College, New York, NY, United States
contact email	davidshy@mskcc.org
lab head
Igor Maksimovic
contact affiliation	Tri-Institutional PhD Program in Chemical Biology
contact email	igm2002@med.cornell.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/2020/05/PXD019204

PRIDE project URI

• PRIDE
  1. PXD019204
     1. Label: PRIDE project
     2. Name: An azidoribose probe to track ketoamine adducts in histone ribose glycation (293T nuclei - LFQ)