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Direct monitoring of protein–protein inhibition using nano electrospray ionization mass spectrometry
| Content Provider | Semantic Scholar |
|---|---|
| Author | Cubrilovic, Dragana Barylyuk, Konstantin Hofmann, Daniela Walczak, Michał J. Gräber, Martin Berg, Thorsten Wider, Gerhard Zenobi, Renato |
| Copyright Year | 2014 |
| Abstract | Dissociation of the TNF-alpha trimer caused by the small-molecule inhibitor SPD304 was monitored using native ESI-MS and ion mobility spectrometry (IMS). Upon addition of the inhibitor, our data clearly indicate partial dissociation of the protein into dimers and monomers. The IMS-MS analysis shows that dimeric ions have their own characteristic drift time distributions, which are different from those of the dimer ions originating in the gas phase due to collision-induced dissociation. We show that only one equivalent of the inhibitor binds to the trimeric form. We also investigated inhibition of heterodimer formation of the survival protein Bcl-xL with the cell death-promoting regions of the proteins Bak and Bad, using the small inhibitors ABT737 and ABT263. We found that ABT737 is more potent than ABT263 in preventing the heterodimerization between Bcl-xL and the Bak and Bad derived BH3 peptides. We could also monitor the mode of binding, which in this case is competitive. These results indicate that native ESI-MS can be widely used to study the inhibition of other relevant protein–protein interactions (PPIs), and provide a good basis for further improvement and identification of small-molecule PPI inhibitors. |
| Starting Page | 2794 |
| Ending Page | 2803 |
| Page Count | 10 |
| File Format | PDF HTM / HTML |
| DOI | 10.1039/C3SC53360C |
| Alternate Webpage(s) | http://www.rsc.org/suppdata/sc/c3/c3sc53360c/c3sc53360c1.pdf |
| Alternate Webpage(s) | https://doi.org/10.1039/C3SC53360C |
| Volume Number | 5 |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
