PXD005895

PXD005895 is an original dataset announced via ProteomeXchange.

Title	A class of reactive acyl-CoA species reveals the nonenzymatic origins of protein acylation
Description	The mechanisms underlying the formation of acyl protein modifications remain poorly understood. By investigating the reactivity of endogenous acyl-CoA metabolites, we found a class of acyl-CoAs that undergoes intramolecular catalysis to form reactive intermediates which non-enzymatically modify proteins. Based on this mechanism, we predicted, validated, and characterized the protein modification: 3-hydroxy-3-methylglutaryl(HMG)-lysine. In a model of altered HMG-CoA metabolism, we found evidence of two additional protein modifications: 3-methylglutaconyl(MGc)-lysine and 3-methylglutaryl(MG)-lysine. Using quantitative proteomics, we compared the ‘acylomes’ of two reactive acyl-CoA species, namely HMG-CoA and glutaryl-CoA, which are generated in different pathways. We found proteins that are uniquely modified by each reactive metabolite, as well as common proteins and pathways. We identified the tricarboxylic acid cycle as a pathway commonly regulated by acylation, and validated malate dehydrogenase as a key target. These data identify a fundamental relationship between reactive acyl-CoA species and proteins, and define a new regulatory paradigm in metabolism.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_04:35:39.348.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Paul Grimsrud
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2017-02-09 02:09:58	ID requested
1	2017-04-11 00:25:29	announced
⏵ 2	2024-10-22 04:35:44	announced	2024-10-22: Updated project metadata.

10.1016/j.cmet.2017.03.006;

Wagner GR, Bhatt DP, O'Connell TM, Thompson JW, Dubois LG, Backos DS, Yang H, Mitchell GA, Ilkayeva OR, Stevens RD, Grimsrud PA, Hirschey MD, A Class of Reactive Acyl-CoA Species Reveals the Non-enzymatic Origins of Protein Acylation. Cell Metab, 25(4):823-837.e8(2017) [pubmed]

curator keyword: Biological

submitter keyword: Glutarylation, HMGylation,Nonenzymatic protein acylation

Matthew D. Hirschey
contact affiliation	Assistant Professor Department of Medicine, Division of Endocrinology, Metabolism, and Nutrition Department of Pharmacology and Cancer Biology Duke University Medical Center
contact email	matthew.hirschey@duke.edu
lab head
Paul Grimsrud
contact affiliation	Duke Molecular Physiology Institute
contact email	paul.grimsrud@duke.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/2017/04/PXD005895

PRIDE project URI

• PRIDE
  1. PXD005895
     1. Label: PRIDE project
     2. Name: A class of reactive acyl-CoA species reveals the nonenzymatic origins of protein acylation