Native ESI-MS and Collision-Induced Unfolding (CIU) of the Complex between Bacterial Elongation Factor-Tu and the Antibiotic Enacyloxin IIa

Baines, Cameron; Sargeant, Jacob; Fage, Christopher D.; Pugh, Hannah; Alkhalaf, Lona M.; Challis, Gregory L.; Oldham, Neil J.

Abstract

Collision-induced unfolding (CIU) of protein ions, monitored by ion mobility-mass spectrometry, can be used to assess the stability of their compact gas-phase fold and hence provide structural information. The bacterial elongation factor EF-Tu, a key protein for mRNA translation in prokaryotes and hence a promising antibiotic target, has been studied by CIU. The major [M + 12H]12+ ion of EF-Tu unfolded in collision with Ar atoms between 40 and 50 V, corresponding to an Elab energy of 480–500 eV. Binding of the cofactor analogue GDPNP and the antibiotic enacyloxin IIa stabilized the compact fold of EF-Tu, although dissociation of the latter from the complex diminished its stabilizing effect at higher collision energies. Molecular dynamics simulations of the [M + 12H]12+ EF-Tu ion showed similar qualitative behavior to the experimental results.

Citation

Baines, C., Sargeant, J., Fage, C. D., Pugh, H., Alkhalaf, L. M., Challis, G. L., & Oldham, N. J. (2024). Native ESI-MS and Collision-Induced Unfolding (CIU) of the Complex between Bacterial Elongation Factor-Tu and the Antibiotic Enacyloxin IIa. Journal of The American Society for Mass Spectrometry, 35(7), 1490-1496. https://doi.org/10.1021/jasms.4c00087

• Journal Article Type: Article
• Acceptance Date: May 20, 2024
• Online Publication Date: Jun 3, 2024
• Publication Date: Jun 3, 2024
• Deposit Date: Jun 10, 2024
• Publicly Available Date: Jun 10, 2024
• Journal: Journal of the American Society for Mass Spectrometry
• Print ISSN: 1044-0305
• Electronic ISSN: 1879-1123
• Publisher: Springer Verlag
• Peer Reviewed: Peer Reviewed
• Volume: 35
• Issue: 7
• Pages: 1490-1496
• DOI: https://doi.org/10.1021/jasms.4c00087
• Keywords: Collisions, Conformation, Energy, Ions, Ligands
• Public URL: https://nottingham-repository.worktribe.com/output/35735016
• Publisher URL: https://pubs.acs.org/doi/10.1021/jasms.4c00087