Jump to main content
Jump to site search
PLANNED MAINTENANCE Close the message box

Scheduled maintenance work on Wednesday 27th March 2019 from 11:00 AM to 1:00 PM (GMT).

During this time our website performance may be temporarily affected. We apologise for any inconvenience this might cause and thank you for your patience.


Issue 21, 2015
Previous Article Next Article

Ion mobility coupled to native mass spectrometry as a relevant tool to investigate extremely small ligand-induced conformational changes

Author affiliations

Abstract

We evaluate the potential of native mass spectrometry (MS) and ion mobility (IM-MS) for the screening of protein : ligand complexes when very subtle conformational changes are involved. As a proof of concept, we investigate the interactions between a peptide deformylase (PDF1B), a promising target for the development of new antibiotics, and three of its specific inhibitors that bind in different modes. First, real-time native MS reveals two types of ligands, both interacting in a 1 : 1 stoichiometry with PDF1B but with different affinities and gas phase stabilities. Conformational IM-MS screening then highlights two very close but significantly distinct ligand-induced conformations with collision cross sections that differ by less than 1%. Real-time IM-MS is used to monitor not only the dynamics of ligand binding to apoPDF1B but also the switching between holo conformations. This study provides additional evidence that the most potent ligands inhibit peptide deformylases through a slow-tight binding mechanism, in agreement with previous structural and enzymology studies. Furthermore, this approach, wherein the characteristics obtained by native MS are combined with IM-MS conformational screening, prove valuable in characterizing extremely subtle dynamic conformational changes induced when ligands bind to protein assemblies. We discuss the promise and limitations of IM-MS in the context of detection of very small conformational changes induced upon ligand binding.

Graphical abstract: Ion mobility coupled to native mass spectrometry as a relevant tool to investigate extremely small ligand-induced conformational changes

Back to tab navigation

Supplementary files

Publication details

The article was received on 30 Jun 2015, accepted on 17 Sep 2015 and first published on 17 Sep 2015


Article type: Paper
DOI: 10.1039/C5AN01311A
Author version
available:
Download author version (PDF)
Citation: Analyst, 2015,140, 7234-7245
  • Open access: Creative Commons BY license
  •   Request permissions

    Ion mobility coupled to native mass spectrometry as a relevant tool to investigate extremely small ligand-induced conformational changes

    J. Stojko, S. Fieulaine, S. Petiot-Bécard, A. Van Dorsselaer, T. Meinnel, C. Giglione and S. Cianférani, Analyst, 2015, 140, 7234
    DOI: 10.1039/C5AN01311A

    This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. Material from this article can be used in other publications provided that the correct acknowledgement is given with the reproduced material.

    Reproduced material should be attributed as follows:

    • For reproduction of material from NJC:
      [Original citation] - Published by The Royal Society of Chemistry (RSC) on behalf of the Centre National de la Recherche Scientifique (CNRS) and the RSC.
    • For reproduction of material from PCCP:
      [Original citation] - Published by the PCCP Owner Societies.
    • For reproduction of material from PPS:
      [Original citation] - Published by The Royal Society of Chemistry (RSC) on behalf of the European Society for Photobiology, the European Photochemistry Association, and RSC.
    • For reproduction of material from all other RSC journals:
      [Original citation] - Published by The Royal Society of Chemistry.

    Information about reproducing material from RSC articles with different licences is available on our Permission Requests page.

Search articles by author

Spotlight

Advertisements