PXD054497

PXD054497 is an original dataset announced via ProteomeXchange.

Title	Structural and systems characterization of phosphorylation on metabolic enzymes identifies sex-specific metabolic reprogramming in obesity
Description	The coordination of cellular signaling networks with metabolic response is key for balanced energy production and homeostasis. This coordination is achieved through spatiotemporal control of metabolism via compartmentalization and redundancies coupled to rapid signaling. Such dynamics must therefore require fast regulatory networks such as those directed by phosphorylation of serine (S) (~90%), threonine (T) (~9%), and tyrosine (Y) (~0.1-1%) residues on metabolic enzymes. In order to determine the structure-function relationship of phosphorylation sites on metabolic enzymes, we leveraged the published phosphoproteome and structural data for metabolic enzymes to stratify phosphorylation sites in the context of functional domains. There was significant enrichment of pY in proximity to functional and dimerization domains.In order to gain network level insight into the pY directed regulation of metabolic enzymes and the resulting dynamics of metabolic reprogramming, we employed proteomics, metabolomics, structural analysis, and computational modeling to characterize the functional impact of pY on enzymes in the context of obesity. We validated the intrinsic role of select phosphosites on enzyme function via enzyme kinetics assays and isotope labeled metabolic tracing. Overall, our multidisciplinary approach bridges the structure-function knowledge gap allowing us to identify the convergence zone where cellular signaling ‘tunes’ metabolism.
HostingRepository	PRIDE
AnnounceDate	2025-05-17
AnnouncementXML	Submission_2025-05-17_09:48:03.796.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD054497
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Tigist Tamir
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	phosphorylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Exploris 480; Q Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2024-08-01 07:28:07	ID requested
⏵ 1	2025-05-17 09:48:04	announced

10.1101/2024.08.28.609894;

10.6019/PXD054497;

Tamir TY, Chaudhary S, Li AX, Trojan SE, Flower CT, Vo P, Cui Y, Davis JC, Mukkamala RS, Venditti FN, Hillis AL, Toker A, Vander Heiden MG, Spinelli JB, Kennedy NJ, Davis RJ, White FM, Structural and systems characterization of phosphorylation on metabolic enzymes identifies sex-specific metabolic reprogramming in obesity. bioRxiv, ():(2024) [pubmed]

submitter keyword: Phosphoproteomics, Metabolomics, Metabolism, LC-MS,Cell Signaling, Obesity

Forest White
contact affiliation	Koch Institute for Integrative Cancer Research Center for Precision Cancer Medicine Department of Biological Engineering Massachusetts Institute of Technology, Cambridge, MA, USA
contact email	fwhite@mit.edu
lab head
Tigist Tamir
contact affiliation	University of North Carolina at Chapel Hill, Department of Biochemistry and Biophysics
contact email	tytamir@mit.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD054497
     1. Label: PRIDE project
     2. Name: Structural and systems characterization of phosphorylation on metabolic enzymes identifies sex-specific metabolic reprogramming in obesity