PXD002304

PXD002304 is an original dataset announced via ProteomeXchange.

Title	MManassantin A iTRAQ-SPROX Drug Mode-of-Action
Description	Manassantin A is a natural product that has been isolated from the perennial herb Saururus chinensis Baill and the aquatic plant Saururus cernuus. Manassantin A has been shown to possess potent hypoxia inducible factor 1 alpha (HIF-1α) inhibitory activity in a cell-based assay screen of thousands of natural products. Manassantin A holds promise as an anti-cancer drug since it has been shown to selectively target tumor cells over normal cells. Due to the complex biological pathways involved in cancer and hypoxia, it is difficult to determine the mode-of-action by which manassantin A inhibits HIF-1. While some of the biological activities of manassantin A have been discovered in various cell-based activity assays, the molecular basis of manassantin A’s biological activities is not well characterized. The proteins in a hypoxic MDA-MB-231 cell lysate were screened for interactions with manassantin A using large scale experiments to uncover novel manassantin A interactions that lead to the drug’s HIF-1 inhibition and anti-cancer activity. Two energetics-based approaches were utilized in this manassantin A mode-of-action study: iTRAQ-SPROX and SILAC-Pulse Proteolysis. In these energetics-based approaches, protein stability is measured using the chemical denaturant dependence of either a methionine oxidation reaction (iTRAQ-SPROX) or a thermolysin protease digest (SILAC-Pulse Proteolysis). Using boh of these techniques, the stability of proteins in the absence and presence of excess manassantin A was monitored to assess ligand-induced protein stability changes.
HostingRepository	PRIDE
AnnounceDate	2016-07-12
AnnouncementXML	Submission_2016-07-12_00:11:04.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Michelle Geer
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	methylthiolated residue; iTRAQ8plex-116 reporter+balance reagent acylated residue; monohydroxylated residue; deamidated residue
Instrument	LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2015-06-05 01:45:53	ID requested
⏵ 1	2016-07-12 00:11:05	announced

Geer Wallace MA, Kwon DY, Weitzel DH, Lee CT, Stephenson TN, Chi JT, Mook RA, Dewhirst MW, Hong J, Fitzgerald MC, Discovery of Manassantin A Protein Targets Using Large-Scale Protein Folding and Stability Measurements. J Proteome Res, 15(8):2688-96(2016) [pubmed]

curator keyword: Biomedical

submitter keyword: manassantin A, MDA-MB-231, Stability of Proteins from Rates of Oxidation (SPROX), drug mode-of-action, iTRAQ, protein-ligand binding interactions

Michael C. Fitzgerald
contact affiliation	Duke University
contact email	michael.c.fitzgerald@duke.edu
lab head
Michelle Geer
contact affiliation	Duke
contact email	ariel.geer79@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD002304
     1. Label: PRIDE project
     2. Name: MManassantin A iTRAQ-SPROX Drug Mode-of-Action