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Discovery of Manassantin A Protein Targets Using Large-Scale Protein Folding and Stability Measurements.

Publication ,  Journal Article
Geer Wallace, MA; Kwon, D-Y; Weitzel, DH; Lee, C-T; Stephenson, TN; Chi, J-T; Mook, RA; Dewhirst, MW; Hong, J; Fitzgerald, MC
Published in: J Proteome Res
August 5, 2016

Manassantin A is a natural product that has been shown to have anticancer activity in cell-based assays, but has a largely unknown mode-of-action. Described here is the use of two different energetics-based approaches to identify protein targets of manassantin A. Using the stability of proteins from rates of oxidation technique with an isobaric mass tagging strategy (iTRAQ-SPROX) and the pulse proteolysis technique with a stable isotope labeling with amino acids in cell culture strategy (SILAC-PP), over 1000 proteins in a MDA-MB-231 cell lysate grown under hypoxic conditions were assayed for manassantin A interactions (both direct and indirect). A total of 28 protein hits were identified with manassantin A-induced thermodynamic stability changes. Two of the protein hits (filamin A and elongation factor 1α) were identified using both experimental approaches. The remaining 26 hit proteins were only assayed in either the iTRAQ-SPROX or the SILAC-PP experiment. The 28 potential protein targets of manassantin A identified here provide new experimental avenues along which to explore the molecular basis of manassantin A's mode of action. The current work also represents the first application iTRAQ-SPROX and SILAC-PP to the large-scale analysis of protein-ligand binding interactions involving a potential anticancer drug with an unknown mode-of-action.

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Published In

J Proteome Res

DOI

EISSN

1535-3907

Publication Date

August 5, 2016

Volume

15

Issue

8

Start / End Page

2688 / 2696

Location

United States

Related Subject Headings

  • Saururaceae
  • Protein Stability
  • Protein Folding
  • Protein Binding
  • Peptide Elongation Factor 1
  • Oxidation-Reduction
  • Lignans
  • Ligands
  • Isotope Labeling
  • Humans
 

Citation

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Geer Wallace, M. A., Kwon, D.-Y., Weitzel, D. H., Lee, C.-T., Stephenson, T. N., Chi, J.-T., … Fitzgerald, M. C. (2016). Discovery of Manassantin A Protein Targets Using Large-Scale Protein Folding and Stability Measurements. J Proteome Res, 15(8), 2688–2696. https://doi.org/10.1021/acs.jproteome.6b00237
Geer Wallace, M Ariel, Do-Yeon Kwon, Douglas H. Weitzel, Chen-Ting Lee, Tesia N. Stephenson, Jen-Tsan Chi, Robert A. Mook, Mark W. Dewhirst, Jiyong Hong, and Michael C. Fitzgerald. “Discovery of Manassantin A Protein Targets Using Large-Scale Protein Folding and Stability Measurements.J Proteome Res 15, no. 8 (August 5, 2016): 2688–96. https://doi.org/10.1021/acs.jproteome.6b00237.
Geer Wallace MA, Kwon D-Y, Weitzel DH, Lee C-T, Stephenson TN, Chi J-T, et al. Discovery of Manassantin A Protein Targets Using Large-Scale Protein Folding and Stability Measurements. J Proteome Res. 2016 Aug 5;15(8):2688–96.
Geer Wallace, M. Ariel, et al. “Discovery of Manassantin A Protein Targets Using Large-Scale Protein Folding and Stability Measurements.J Proteome Res, vol. 15, no. 8, Aug. 2016, pp. 2688–96. Pubmed, doi:10.1021/acs.jproteome.6b00237.
Geer Wallace MA, Kwon D-Y, Weitzel DH, Lee C-T, Stephenson TN, Chi J-T, 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. 2016 Aug 5;15(8):2688–2696.
Journal cover image

Published In

J Proteome Res

DOI

EISSN

1535-3907

Publication Date

August 5, 2016

Volume

15

Issue

8

Start / End Page

2688 / 2696

Location

United States

Related Subject Headings

  • Saururaceae
  • Protein Stability
  • Protein Folding
  • Protein Binding
  • Peptide Elongation Factor 1
  • Oxidation-Reduction
  • Lignans
  • Ligands
  • Isotope Labeling
  • Humans