Probing the Conformational and Functional Consequences of Disulfide Bond Engineering in Growth Hormone by Hydrogen–Deuterium Exchange Mass Spectrometry Coupled to Electron Transfer Dissociation

2015 ◽  
Vol 87 (12) ◽  
pp. 5973-5980 ◽  
Author(s):  
Signe T. Seger ◽  
Jens Breinholt ◽  
Johan H. Faber ◽  
Mette D. Andersen ◽  
Charlotte Wiberg ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Growth Hormone ◽  
Electron Transfer ◽  
Disulfide Bond ◽  
Electron Transfer Dissociation ◽  
Hydrogen Deuterium Exchange ◽  
Exchange Mass Spectrometry ◽  
Hydrogen Deuterium ◽  
Functional Consequences ◽  
Deuterium Exchange Mass Spectrometry

scholarly journals Analysis of phosphoinositide 3-kinase inhibitors by bottom-up electron-transfer dissociation hydrogen/deuterium exchange mass spectrometry

2017 ◽  
Vol 474 (11) ◽  
pp. 1867-1877 ◽  
Author(s):  
Glenn R. Masson ◽  
Sarah L. Maslen ◽  
Roger L. Williams
Keyword(s):  
Mass Spectrometry ◽  
Electron Transfer ◽  
Electron Transfer Dissociation ◽  
Deuterium Exchange ◽  
Hydrogen Deuterium Exchange ◽  
Exchange Mass Spectrometry ◽  
Hydrogen Deuterium ◽  
Deuterium Exchange Mass Spectrometry ◽  
Phosphoinositide 3 Kinase ◽  
Hdx Ms

Until recently, one of the major limitations of hydrogen/deuterium exchange mass spectrometry (HDX-MS) was the peptide-level resolution afforded by proteolytic digestion. This limitation can be selectively overcome through the use of electron-transfer dissociation to fragment peptides in a manner that allows the retention of the deuterium signal to produce hydrogen/deuterium exchange tandem mass spectrometry (HDX-MS/MS). Here, we describe the application of HDX-MS/MS to structurally screen inhibitors of the oncogene phosphoinositide 3-kinase catalytic p110α subunit. HDX-MS/MS analysis is able to discern a conserved mechanism of inhibition common to a range of inhibitors. Owing to the relatively minor amounts of protein required, this technique may be utilised in pharmaceutical development for screening potential therapeutics.

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