PXD002305 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Manassantin A SILAC-Pulse Proteolysis |
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 | 2016-07-19 |
AnnouncementXML | Submission_2016-07-19_03:27:46.xml |
DigitalObjectIdentifier | https://dx.doi.org/10.6019/PXD002305 |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Supported dataset by repository |
PrimarySubmitter | Michelle Geer |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | 6x(13)C: 4x(15)N labeled L-arginine; 6x(13)C: 2x(15)N labeled L-lysine; iodoacetamide - site C: 57.021464; L-methionine sulfone: 31.989829 |
Instrument | 6520 Quadrupole Time-of-Flight LC/MS |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2015-06-05 01:46:13 | ID requested | |
⏵ 1 | 2016-07-19 03:27:48 | announced | |
Publication List
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] |
Keyword List
curator keyword: Biomedical |
submitter keyword: manassantin A, MDA-MB-231, pulse proteolysis, drug mode-of-action, Stable Isotope Labeling of Amino Acids in Cell culture, in-gel digestion |
Contact List
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 | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD002305
- Label: PRIDE project
- Name: Manassantin A SILAC-Pulse Proteolysis