Small-Molecule Inhibition of c-MYC:MAX Leucine Zipper Formation Is Revealed by Ion Mobility Mass Spectrometry

2012 ◽  
Vol 134 (47) ◽  
pp. 19384-19392 ◽  
Author(s):  
Sophie R. Harvey ◽  
Massimiliano Porrini ◽  
Christiane Stachl ◽  
Derek MacMillan ◽  
Giovanna Zinzalla ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Small Molecule ◽  
Ion Mobility ◽  
Leucine Zipper ◽  
Ion Mobility Mass Spectrometry ◽  
Small Molecule Inhibition

scholarly journals Exploring the conformational landscape and stability of Aurora A using ion-mobility mass spectrometry and molecular modelling

2021 ◽  
Author(s):  
Lauren J. Tomlinson ◽  
Matthew Bachelor ◽  
Dominic P. Byrne ◽  
Joscelyn Sarsby ◽  
Philip J. Brownridge ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Protein Kinase ◽  
Crystal Structures ◽  
Small Molecule ◽  
Ion Mobility ◽  
Protein Kinase Inhibitors ◽  
Ion Mobility Mass Spectrometry ◽  
Aurora A ◽  
Kinase Signaling ◽  
Conformational Landscape

Protein kinase inhibitors are proving highly effective in helping treat a number of non-communicable diseases driven by aberrant kinase signaling. They are also extremely valuable as chemical tools to help delineate cellular roles of kinase signaling complexes. The binding of small molecule inhibitors induces conformational effects on kinase dynamics; evaluating the effect of such interactions can assist in developing specific inhibitors and is deemed imperative to understand both inhibition and resistance mechanisms. Using gas-phase ion mobility-mass spectrometry (IM-MS) we characterized changes in the conformational landscape and stability of the protein kinase Aurora A (Aur A) driven by binding of the physiological activator TPX2 or small molecule inhibition. Aided by molecular modeling, we establish three major confor-mations: one highly-populated compact conformer similar to that observed in most crystal structures, a second highly-populated conformer possessing a more open structure that is infre-quently found in crystal structures, and an additional low-abundance conformer not currently represented in the protein databank. Comparison of active (phosphorylated) and inactive (non-phosphorylated) forms of Aur A revealed that the active enzyme has different conformer weight-ings and is less stable than the inactive enzyme. Notably, inhibitor binding shifts conformer balance towards the more compact configurations adopted by the unbound enzyme, with both IM-MS and modelling revealing inhibitor-mediated stabilisation of active Aur A. These data highlight the power of IM-MS in combination with molecular dynamics simulations to probe and compare protein kinase structural dynamics that arise due to differences in activity and as a result of compound binding.

scholarly journals The use of ion mobility mass spectrometry to probe modulation of the structure of p53 and of MDM2 by small molecule inhibitors

2015 ◽  
Vol 2 ◽  
Author(s):  
Eleanor R. Dickinson ◽  
Ewa Jurneczko ◽  
Judith Nicholson ◽  
Ted R. Hupp ◽  
Joanna Zawacka-Pankau ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Small Molecule ◽  
Ion Mobility ◽  
Small Molecule Inhibitors ◽  
Ion Mobility Mass Spectrometry

How useful is molecular modelling in combination with ion mobility mass spectrometry for ‘small molecule’ ion mobility collision cross-sections?

The Analyst ◽  
2015 ◽  
Vol 140 (20) ◽  
pp. 6814-6823 ◽  
Author(s):  
Cris Lapthorn ◽  
Frank S. Pullen ◽  
Babur Z. Chowdhry ◽  
Patricia Wright ◽  
George L. Perkins ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Cross Section ◽  
Small Molecule ◽  
Cross Sections ◽  
Ion Mobility ◽  
Molecular Modelling ◽  
Collision Cross Section ◽  
Ion Mobility Mass Spectrometry ◽  
Collision Cross Sections

Evaluation of N2(g) and He(g) MOBCAL collision cross section values from 20 compounds ∼ m/z 122 to 609.

Rapid Diagnosis of Parkinson’s Disease from Sebum using Paper Spray Ionisation Ion Mobility Mass Spectrometry

2020 ◽  
Author(s):  
Depanjan Sarkar ◽  
Drupad Trivedi ◽  
Eleanor Sinclair ◽  
Sze Hway Lim ◽  
Caitlin Walton-Doyle ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Ion Mobility ◽  
Neurodegenerative Disorder ◽  
Treatment Options ◽  
Ion Mobility Mass Spectrometry ◽  
Paper Spray ◽  
Molecular Features ◽  
Validation Set

Parkinson’s disease (PD) is the second most common neurodegenerative disorder for which identification of robust biomarkers to complement clinical PD diagnosis would accelerate treatment options and help to stratify disease progression. Here we demonstrate the use of paper spray ionisation coupled with ion mobility mass spectrometry (PSI IM-MS) to determine diagnostic molecular features of PD in sebum. PSI IM-MS was performed directly from skin swabs, collected from 34 people with PD and 30 matched control subjects as a training set and a further 91 samples from 5 different collection sites as a validation set. PSI IM-MS elucidates ~ 4200 features from each individual and we report two classes of lipids (namely phosphatidylcholine and cardiolipin) that differ significantly in the sebum of people with PD. Putative metabolite annotations are obtained using tandem mass spectrometry experiments combined with accurate mass measurements. Sample preparation and PSI IM-MS analysis and diagnosis can be performed ~5 minutes per sample offering a new route to for rapid and inexpensive confirmatory diagnosis of this disease.

P‐97: Separation of Isomeric OLED Materials Using Ion Mobility‐Mass Spectrometry (IM‐MS)

2021 ◽  
Vol 52 (1) ◽  
pp. 1444-1447
Author(s):  
Hirotaka Shioji ◽  
Azusa Uematsu ◽  
Motoshi Onoda ◽  
Keiko Matsuda ◽  
Keisuke Sawada ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Ion Mobility ◽  
Ion Mobility Mass Spectrometry
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